m2m final

What is Cas9? Why is it so amazing and important?

CRISPR ASsociated protein 9 - RNA-guided DNA endonuclease enzyme. This means that you can give Cas9 any strand of RNA as a guide to go off and find a place to cut DNA with a complimentary sequence to the guide RNA. Like a programmable restriction endonuclease.

Describe the role of stem cells in the initiation and maintenance of cancerous tumors. How is this pertinent to treatment methods?

Cancer now known to be composed of very few/rare cancer stem cells that cause tumor growth and then bulk tumors cells that do not cause growth. Cancer drugs now looking to target only cancer stem cells, leaving tumor to degrade and die off.

What does the drug Vorinostat do?

Cancer treatment drug. Blocks HDACs. ----Normally this would make NO sense as you want to stop cell growth and proliferation (stop transcription) but apparently Vorinostat turns back on genes involved in cell differentiation that are turned off in cancer.

RNA poly II had a C Terminal Domain. What protein phosphorylates this? What does that phosphorylation do?

Cdk7 (Part of TFIIH) phosphorylates the CTD. This phosphorylation of CTD signals RNA poly II to clear the promotor and initiate elongation.

Explain the basic mechanisms of cell death regulation by mitochondria.

Cell damage or intrinsic pathway triggers Bak/Bax to permeabilize the outside of the mitochondria outer membrane releasing Cytochrome C into the cytoplasm. Cytochrome C bind proteins making the apoptosome which activates the caspases involved in apoptosis.

List a protein modification (phosphorylation) that can alter the activity of a sequence specific DNA binding protein, and explain the mechanism by which the activity is altered.

CREB protein - sits bound to DNA in inactive form. If it becomes phosphorylated, then recruits CBP (has HAT activity), and RNA pol II.

What is cytogenetics?

Cell genetics. Chromosomes Cytogenetics is a branch of genetics that is concerned with the study of the structure and function of the cell, especially the chromosomes.[1] It includes routine analysis of G-banded chromosomes, other cytogenetic banding techniques, as well as molecular cytogenetics such as fluorescent in situ hybridization (FISH) and comparative genomic hybridization (CGH).

Explain who cilia are assembled

Cell is in G1. Mother centriole is capped by ciliary vesicle, now is basal body. MT doublets now assemble on the ciliary vesicle.

Which class of CF is the F508Del?

Class 2.

What are the 4 classification of DNA binding domains? How are they classified?

Classified based on tertiary structure of DNA binding domain. 1) Homeodomain (helix-turn-helix) 2) Zinc Finger 3) Basic Leucine Zipper 4) Helix-loop-helix

What are the two methods by which vesicles are formed in endocytosis?

Clathrin coated vesicle OR Calveolae - smaller, more abundant, invaginations in the cell surface.

What are the three coat proteins for vesicular compartments?

Clathrin, COP1, and COP2

How is membrane-fusion specificity regulated in the cell?

Correct combination of SNARE proteins needed for fusion. Certain SNARE proteins will not bind with others.

Compare and contrast the structure of exocrine and endocrine glands

Exocrine - secretory units and ducts that secrete materials onto epithelia-lined surfaces or the outside world. Endocrine - No ducts. Secretory cells surrounded by basal lamina and secrete substances across basal lamina directly into blood stream.

What are the two ways in which a gland secretes its substance?

Exocytosis - most common, package and export Disintegration - whole cell disintegrates which leads to enter cellular contents becoming part of the secretion

If a dsDNA strand is broken bluntly across both strands, what must occur before HR can repair this?

Exonuclease activity on the 5' end of either break, leaving 3' overhang.

True or False ATP-bound Myosin heads stay bound to actin. (AKA rigor conformation.)

FALSE ATP binding to myosin decreases myosin affinity for actin. Lack of ATP leaves Myosin bound to actin. Think how dead organisms undergo rigor mortis, muscle stiffness, all myosin is bound and inactive.

True or False SNARES form an anti-parallel coiled coil

FALSE All a-helices are in parallel in SNARE complex.

True or False All GAGs are synthesized in the golgi

FALSE All are except for hyaluronic acid which is synthesized at the plasma membrane.

True or False Cartilage and Bone can both be generated (grow) interstitially

FALSE Bone can only grow at its surface where cartilage can grow internally (interstitially)

True or False LCR is only on Chr 11 (Beta and beta globin like)

FALSE Both alpha and beta have LCRs

True or False Skeletal muscle, under voluntary control, can contract without the use of Ca++

FALSE Ca++ is essential to the contraction of all 3 types of muscle.

True or False Vm can be calculated using ions to which membrane is not permeable

FALSE Can only use ions to which the cell's membrane is permeable in calculating Vm (which will also =E for the permeable ions). If not permeable to an ion, you are calculating that ion's Em, not the Vm.

True or False Smooth muscle cells have a t-tubule system

FALSE Cells are so small that Ca can defuse rapidly enough, not needing t-tubule system required by larger diameter cells.

True or false Gamma Globin is more towards 5' end of chromosome 16 than Delta Globin

FALSE Chr 16 is the alpha globins. But yes, on Chr 11 Gamma is more 5' than delta as it is expressed first.

True or False UC affects the upper GI

FALSE Crohn's affects upper GI. (and can apparently affect the lower GI all the way to external anus via info from our Vignette)

True or False Elastin is a type of collagen

FALSE Elastin is an elastic fiber protein, not a collagen protein. Different protein makeup.

True or False Extracellular material cannot end up in an autophagosome.

FALSE Endosomes can fuse with autophagosomes on their way to the lysosomes. In this way, autophagy can ALSO degrade extra cellular material.

True or False Uncompetitive inhibitors bind enzymes regardless of whether or not that enzyme has a bound substrate

FALSE Enzyme must have bound substrate in order for non-competitive inhibitors to bind.

True or False Increasing Epsilon globin production in an a-thalassemia patient can benefit the patient.

FALSE Epsilon is a beta globing-like globin. beta globin is not deficient in a-thalassemia.

True or False All skeletal muscles in the human body are innervated at a single spot, normally near the center of the cell.

FALSE Extra ocular eye muscle cells will typically have multiple innervations.

True or False Barrier nucleoporins contain Phenylalanine and Glutamine repeats.

FALSE FG repeats. So Phenylalanine (F) and Glycine (G) repeats.

True or False Genes in the same gene family must be on the same chromosome. Give an example to support your answer

FALSE Genes in the same family can be on different chromosomes. EX: Hemoglobin subunits - 10 genes on two different chromosomes. (alpha and beta-globin loci)

True or false Achrondroplasia causes lack of cognitive development.

FALSE HYPOchondroplasia does. Achondroplasia does not.

True or False Desmosomes are only formed between epithelial cells.

FALSE Hemidesmosomes are involved in epithelial cell binding to the basal lamina

True or False Polar positively charged amino acids are in their protonated(H+) form because their pKa is less than the surrounding pH

FALSE If pKa < pH than the AA is deprotonated (such as with the NEGATIVE polar amino acids)

True or False No normal gametes are produced if a nondisjunction occurs at any point Meiosis.

FALSE If the non-disjunction occurs in Meiosis II, then 50% of the haploid gametes are normal.

True or False Vimentin and keratin filaments can incorporate various monomers into the growing chain

FALSE Intermediate filaments such as vimentin and keratin can only contain homo-monomers.

True or False The Autophagosome has a single membrane barrier between its contents and the cytosol.

FALSE It has a double membrane.

True or False Autophagy is only cell-protective, imparting only positive survival effects on cells.

FALSE It is also a player in cell death.

True or False The outer layer of the nuclear envelope is continuous with the golgi apparatus.

FALSE It is continuous with the rough Endoplasmic Reticulum.

True or False A and B toxin are produced by the vibrio cholera bacteria

FALSE It is produced by a bacteriophage (virus) that infects the bacterial cell.

True or False Epsilon-globin is an alpha-globin-like protein

FALSE Its a beta-globin like protein.

True or False FGFR3 is on the q arm of Chromosome 4 at nucleotide 1138

FALSE Its on the p arm. Chromosome 4p16.3 nucleotide 1138

True or False The ATG genes are only involved in autophagy

FALSE Many functions, many unknown, this is why it is hard to Rx control ATG genes without causing other problems.

True or False Methylation of the C in a CG pair alters their base pairing.

FALSE Methylation of the C in a CG pair does not alter their base pairing.

Describe the consequences of demyelination in nerve conduction.

Demyelination leaves area devoid of Na ion channels. Na ion channels proliferate and fill the void. Increased Na intake into cell slows its conduction.

What shape does a mobile cell adopt in a dense ECM? And in a lose ECM?

Dense - Elongated form Lose - Round Shape, ameboid.

True or False The basolateral side of epithelial cells is defined by microvilli

FALSE Microvilli are on the apical side of epithelial cells.

A given molecule with a pKa of 5.5 is placed in a pH 7.4 solution (the human body). Does the protonated or deprotonated form of the molecule prevail?

Deprotonated. Because the pKa < PH Amino Acid COOH and NH groups: Pic shows pKa for carboxyl group on left and of amine group on the right. That is why carboxyl group is deprotonated and amine group is protonated in human body

True or False Once Ca moves tropomyosin out of the way for myosin to bind actin, ATP is still needed for a power stroke

FALSE Myosin head is already 'cocked', just needs the open binding site, then it binds and exerts power stroke landing in rigor conformation. ATP is needed to alleviate rigor conformation.

True or False NHEJ requires DNA ends that have 3' overhangs.

FALSE NHEJ requires protected (blunt) , even ends. HR requires the 3' overhangs.

True or False In order for a protein to be imported into the nucleus it must have an NLS

FALSE NLS is necessary for import into the nucleus, but a protein does not have to have it if it simply binds to a different protein that does have it.

True or False Action potential is a huge cellular permeability to K+ followed by a huge cellular permeability to Na+

FALSE Na+ then K+.

What does Edman Degradation do?

Determines N-terminal sequence of protein.

What is chaperone-based therapy?

Development of synthetic chaperones that bind near active site of mutated enzyme to stabilize it, help transport it, and get it to target substrate. Only works with mutations that do not cause major defects in protein.

True or False The term non-disjunction only applies to events occurring in Meiosis I and II

FALSE Non-disjunction can also apply to Mitosis where sister chromatids fail to separate.

True or False Both cardiac and skeletal muscle have gap junctions between concentric cells

FALSE Only cardiac muscle. Potentials ara passed from cell to cell.

What is m-TOR? What does it do in regards to translation? What class of protein is m-Tor?

Direct effects on up and down regulation of both Elongation Factors and Release factors. One route is for M-TOR to phosphorylate 4E-BP which blocks 4E-BP activity. This allows ELF-4E to proceed to bind 5' cap Class: Kinase, it phosphorylates targets.

True or False Men with a mutation in their mitochondrial DNA can pass this on to a fraction of their offspring

FALSE Only females can pass on mitochondrial-related traits as all mitochondria in the adult human body stem from the mitochondria in the initial female ovum. Sperm carry no mitochondria.

True or False Osteocytes play a large role in production of bone matrix

FALSE Only osteoblasts contribute to bone matrix formation. Osteocytes can modify the matrix a bit, but no contribution of material.

True or False Cardiac muscle has satellite cells

FALSE Only skeletal.

True or False Mesenchymal stem cells also form osteoclasts.

FALSE Osteoclasts are not a product of the MSC/Fibroblast pathways, they are formed from hematopoietic stem cells in the bone marrow.

True or False Phosphorylation activates BOTH p53 and Rb

FALSE Phosphorylation activates p53, and inactivates Rb.

True or False Post translational AA modifications only occur in disease related cases.

FALSE Post translational AA modifications are a normal process occurring within the body. Necessary for certain protein function.

What is the testing procedure for LFS and LFL?

Direct sequencing of the entire gene of p53 (more than 2300 base pairs). If no detectable p53 mutations, may test other genes i.e. hChk2, PTEN. Some groups in the past only sequence the "hot spots" which include exons 5-9. Other groups sequence the entire p53 messenger RNA.

True or False Proteins must be unfolded in both passage through the NPC and in co-translational translocation.

FALSE Proteins are completely folded in passage through the NPC but must be unfolded in co-translational translocation.

True or False GAPs act to hydrolyze GTP in Ras

FALSE Ras IS the GTPase. Proteins like GAPs and GEFs act to affect the inherent GTPase activity of Ras.

Where does a competitive inhibitor bind? How does competitive inhibition affect kcat? Km?

Directly to the enzyme. kcat - stays the same (enzyme 'speed' still the same) Km - increases as [I] increases. (more inhibitor competing for active site with substrate, the more substrate you will need to hit 1/2Vmax)

Histologically, what is the appearance of cardiac muscle in HCM?

Disarray.

True or False Myosin, in the rigor conformation, is ADP bound

FALSE Rigor conformation is the myosin, tightly adhered to actin, in 'finished' power stroke formation. ADP has been released by then.

True or False Smoking has no effect on the severity of Crohn's

FALSE Severity directly increases with smoking

True or False Smoking has no effect on the severity of UC

FALSE Smoking is PROTECTIVE for UC. Decreased severity.

True or False Having duplicates of any of the genes from the x chromosome in women results in a defect, that is why x-inactivation occurs.

FALSE Some genes on the inactivated X are still transcribed (10-15%) and therefore have both alleles of that gene active.

True or False Phospholipids and Sphingolipids are both derived from Glycerol

FALSE Sphingomyelin is the source for the hydrophilic end of sphingolipids. All phospholipids have a glycerol derived hydrophilic component.

True or False Epithelial cells do not play a functional role in any organs other than lining surfaces for controlled diffusion.

FALSE The Kidney, liver, and pancreas are composed mostly of epithelial cells, which are the functioning unit.

True or False AP have directionality on an axon (they can only go one direction from where they are initiated)

FALSE The action potential can travel both directions on an axon. That is why if an AP initiates midway through an axon it shoots AP out in two directions.

True or False The initial cartilage model used for long bone formation initiates by appositional growth but then only proceeds growing by an interstitial mechanism.

FALSE The initial cartilage model continually grows by BOTH appositional and interstitial growth until the time of ossification. At that time it is only interstitial growth.

True or False Stereocilia are cilia found in the sensory cell of the ear and function in the reception of sound

FALSE They are NOT cilia, but are microvili. Yes, I know, I'm being tricky. The rest is true.

True or False Integrins are homodimers of transmembrane proteins that associate with the ECM and intercellular actin

FALSE They are heterodimer. But they DO associate with and bind ECM components and communicate internally with actin.

True or False Tight Junctions bind epithelial cells to one another near the basal membrane

FALSE They bind cells to one another near the apical side of the epithelial cells.

True or false AA chains can rotate around their peptide bonds?

FALSE They can't rotate around peptide bonds, they CAN rotate around the other two types of bond in the polypeptide backbone. Phi and Psi bonds. See pic

True or False Hormones do not cross the basal lamina directly but circumnavigate the lamina via a specific pathway.

FALSE They cross the basal lamina.

True or False Muscles grow via muscle cell proliferation

FALSE They grow by increasing the # of myofibrils (girth) and the number of nuclei (length) per cell. Recall that it is bad to increase diameter of myofibrils because this would limit Ca diffusion. So the number of Myofibrils must increase.

True or False Stop transfer and start transfer (signal anchor) sequences are hydrophilic

FALSE They must imbed in to the lipid-bilayer of the plasma membrane and therefore must be hydrophobic.

True or False You can begin to determine the sex of a fetus at the time of the 6th week of pregnancy.

FALSE This is still an indeterminate phase. You can begin to determine sex at the 7th week.

True or False Androgen receptor (AR) is a transmembrane receptor that binds androgens (testosterone, DHT, etc..) and signals activation of transcription within the cell.

FALSE Though it is a receptor, it is free in the cytoplasm, not bound in the membrane. Androgens can pass the plasma membrane.

True or False Stem cells typically replicate/divide rather quickly and often.

FALSE Tight regulation here slows this proliferation greatly, hence the need for transit amplifying cells in rapidly regenerating tissues (skin, gut epithelia...)

True or False Carriers of balanced translocations (no abnormal phenotype) always have an increased risk to develop unbalanced progeny

FALSE While their risk can be increased in many cases, it is not always increased. 0% - 30%

True or False In skeletal muscle, the presence of unregulated ATP is enough to induce contraction on its own.

FALSE Without calcium, there is no muscle contraction.

True or False XIST transcribed from one X-chromosome can inactivate the other X chromosome.

FALSE XIST always acts on the same chromosome from which it was transcribed.

What ocular clinical presentation is common in Marfans?

Ectopia Lentis - displacement of the lens of the eye from its normal location.

Which protein that binds the 5' cap is essential for translation of the mRNA message?

ElF4E

Where does elastase come from? What does it do (in lungs)?

Elastase is produced by neutrophils (certain type of WBC) in the airway. Its action is to break down elastin which weakens connective tissues.

True or False XIST is a protein that wraps one of the two X-chromosomes and causes promoter regions of genes along the chromosome to become methylated, thereby inactivating genes.

FALSE XIST is a long non coding RNA. Not a protein.

True or False With no a-globin present the b-globin can form tetramers and still transport oxygen leading to viable bodily function.

FALSE no a-globin leads to death.

True or False The Paramesonephric ducts give rise to the male sexual structures

FALSE the MESONEPHRIC ducts give rise to the male sexual structures.

What are the elastic ECM fibers and their purpose?

Elastin and Fibrilin. Elastin - protein conformation is random coil that can stretch and recoil. Fibrilin - interweaves elastin fibers, helps organize the elastin fibers. Together these fibers can endure tensile force and recoil back to original confirmation imparting elasticity to the ECM.

In regards to relative charge, the insides of cells are ___________ and the outsides are ___________

Electro negative - inside Electro Positive - outside

What is epigenetics? What is an example we have previously discussed?

Epigenetics - cellular and physiological phenotypic trait variations that are caused by external or environmental factors that switch genes on and off and affect how cells read genes instead of being caused by changes in the DNA sequence. EX: Histone modification and Methylation

What type of tissue is a gland?

Epithelial

What cytoskeleton fibers form the microvilli of epithelial cells? and the structure of axons?

Epithelial cells - actin filaments Axons - Microtubules

Where are two places in the body where motile cilia are located?

Epithelial lining of airways - move mucous and junk Epithelial lining of Fallopian Tubes - movement of ovum towards uterus.

From which type of tissue are most cancers derived? Why?

Epithelial tissue. Damage exposure and their high stem-cell driven turnover rates.

True or False Skin damaged down to the basal lamina (such as a full thickness burn) can still self repair using epithelial stem cells.

FALSE Destroying down to the basal lamina destroys these stem cells. Skin damaged this deeply must be cut out and grafts from other parts of the body must be used for repair.

True or False No rNTPs are used (or bound into the growing chain) in the initiation step of transcription

FALSE Initiation binds the first two rNTPs of the future mRNA

True or False Cleavage of the bHLH region of SREBP occurs at the ER

FALSE It occurs in the golgi

True or False All enzymes and their active sites are protein (AAs)

FALSE RNA has enzymatic activity on its own.

True or False The G.I tract regulates most of the uptake of nutrients, fluids, etc

FALSE The G.I. tract absorbs just about everything. The Kidneys have to regulate levels in the body. GI will select certain isomers from others, but does not have active regulation of uptake overall.

True or False Turner patients present with secondary amenorrhea

FALSE They present with primary amenorrhea Primary - never had a menstrual cycle Secondary - having normal menstrual cycle then a halt for at least 6 months.

True or False Ub is only used in protein degradation

FALSE. Can be attached in single or multiple locations on other proteins, used in signaling. Only POLYubiquitin addition (4 or more in single chain) lead to degradation.

True or False Carriers for the autosomal recessive Sickle Cell have no cellular presentation of the illness

FALSE. Carriers still have some HbS present and therefore some cellular distortion. Pic - (protein gel) 4th from right. Heterozygote.

True or False The Alpha and Beta subunits of Hexosaminidase A are encoded by two different genes on the same chromosome

FALSE. Two different genes on DIFFERENT chromosomes HEXA - Chr 15q23-24 HEXB - Chr 5q13

True or False You can still visualize un-dyed tissue cells.

FALSE....mostly Only naturally pigmented tissues are visible without dye. You can only see what you dye.

True or false: The 60S subunit joins the 40S subunit at the location of the Kozak sequence

FALSE: The 60S does not join until the 40S until the 40S has scanned the RNA, located the AUG codon, and halted there.

True or False: Translation in eukaryotes cannot occur without a 5' cap

FALSE: While Elf4E is essential for normal translation, the IRES pathway (described later) offers a route around cap-dependent translation.

True or False: In Prokaryotes, Transcription and Translation cannot occur simultaneously on the same mRNA

FALSE: An mRNA transcript in prokaryotes, as it emerges from the RNA polymerase, can start binding ribosomes and begin translation.

What gene is mutated in Marfan's? What protein is made?

FBN1 - Fibrillin- extracellular matrix protein

What is the molecular mechanism of Marfans?

FBN1 mutated -> LOF of Fibrillin (extracellular matrix protein, strength of connective tissue) -> affects any WT/normal Fibrillin -> Severe reduction in the number of microfibrils

What gene is affected in Achondroplasia? What is the specific mutation?

FGFR3 - Fibroblast Growth Factor Receptor 3 Amino acid substitution - missense mutation Gly380Arg

What does FGFR3 do?

FGFR3 gene -> Fibroblast Growth Factor Receptor 3 Protein. FGFR3 protein in bone cells regulates bone growth by limiting the formation of bone from cartilage (ossification), particularly in the long bones.

What protein is involved in most straight (non-branched) actin polymers?

FH2. Formins. Spontaneous polymers of only actin are rare. Formins mimic the shape of actin monomers but they readiliy bind, forming actin polymers.

How does Familial Hypertrophic Cardiomyopathy (FHC) relate to myofibril function?

FHC mutations can be in either the myosin heads or the troponin that act to limit contractile strength per myofibril. Thus, single amino acid mutations in the regulatory regions of a myofilament protein or a regulatory protein produce muscle disease.

What gene is mutated in Fragile X?

FMR1 - Fragile X mental retardation 1

What gene is mutated in Fragile-x syndrome? What protein does it make?

FMR1 -> FMRP (protein)

What protein is coded for by FMR1? What does it do?

FMRP - Fragile X Mental Retardation Protein (really??) Protein, found in brain, essential for normal cognitive development.

What is FISH? Describe the mechanism.

Fluorescence In-Situ Hybridization - a cytogenetic technique that uses fluorescent probes that bind to only those parts of the chromosome with a high degree of sequence complementarity. This can differentiate chromosomes form one another based on the specific genes whiten each that you can generate probes for. Normally green and red probe, If both probes end up overlapping they generate yellow.

Describe the events that occur following wounding and subsequent inflammation.

Following wounding, ECM cells... (i) increase water permeability of capillary endothelia leading to swelling, (ii) increase cellular permeability of endothelia, to promote migration of monocytes, lymphcytes and other blood cells into the C.T., (iii) attract migration of white cells to the site of the wound (chemotaxis), (iv) stimulate proliferation of fibroblasts and differentiation of monocytes into macrophages.

What is the function of Ran in nuclear transport out of the nucleus?

GTP bound Ran binds to transport-facilitating protein which binds its cargo at the NES -> Export through NPC -> GTP hydrolysis -> Release of transport protein and cargo into cytoplasm.

What is enthalpy? What does the ∆H sign (Pos/Neg) indicate?

H of the Gibbs free energy equation. - The inherent bond energy in the molecules. ∆H is change in enthalpy. Negative ∆H = heat is released, exothermic. Favorable Positive ∆H = Heat is absorbed, endothermic, unfavorable.

What other molecules does hemoglobin transport? What is the Bohr effect?

H+ and CO2. Both also alter Hemoglobin binding affinity for O2. Bohr Effect. Higher pH (lung) = more O2 affinity. Lower pH (tissue) = less.

What is the primary shaping force in protein's secondary structure?

H-bonds

What is hyaluronic acid?

HA is a GAG that contributes to hydration and viscosity of the ECM. Major component in synovial fluid. Associated with hyaline cartilage. HA is different than most GAGs in that it is a molecule that is NOT covalently bound to a protein core.

What is the name of the homodimeric enzyme HEXA/HEXA?

HexS.

What enzyme is deficient in Tay-Sachs?

Hexosaminidase A

Things may be repeated throughout this deck. Sorry bout that. Just consider it revisiting a topic from several different angles. :)

Hi.

How can eIF2 be used to regulate translation?

IF eIF2 is phosphorylated, it is inactive, no delivery of the initiation tRNA to AUG codon, no initiation. Multiple pathways trigger this, shown in pic. Double stranded RNA - normally a sign of viral infection. Halt translation.

What are the initiation factor proteins in prokaryotic initiation? What do each of them do?

IF1 - Binds 30S subunit IF2 - Brings Met loaded initiation tRNA to bind with AUG in p-site of 30S subunit. IF3 - Binds 30S subunit

What causes the release of the initiation factors from the assembling ribosome? What does this lead to?

IF2 is bound to GTP. GTP hydrolysis to GDP on IF2 causes all IFs to depart allowing the 50S subunit to bind the 30S, assembling the ribosome.

What is a way in which eukaryotic cells can bypass cap-dependent translation and translate without eIF-4E?

IRES RNA elements can recruit 40S subunit without the eIF-4E cap. These elements function in normal cells. Therefore in cells where the cap pathway is blocked or damages, the cell can still translate a small amount of target mRNAs.

Why and how does NHEJ lose nt in the repair?

If DS break leaves overhangs, the overhangs are cleaved off in an effort to make the NHEJ-necessary blunt end, and the genetic info cleaved is lost. Leads to genetic diversity.

How are CDK and the Pre-Replication Complex related to replication origin regulation?

High CDK blocks Pre-RC assembly (no new Pre-RCs) Low CDK allows Pre-RC to assemble (Gather at Origin) BUT High CDK is also needed to activate the Pre-RCs (more specifically the helicases). So in S phase when replication is underway, no new Pre-RCs can be constructed because High CDKs block new Pre-RC assembly. This limits the number of Active origins. No new Pre-RC once replication (s-phase) underway.

Why is the timing of a PKU test for a newborn important?

If you test too early the baby still has maternal PAH in system, so normal phe-tyr levels will be present in a child that may have PKU. If you test too late you may risk the baby getting poisoned by normal foods (protein in breast milk). Must start treatment before this.

How can you lose heterozygosity in Holliday junction resolution?

If, instead of using the sister chromatid for the HR (identical), you use the homologous chromosome (potentially different sequence), for Holliday Junction resolution. This results in a loss of heterozygosity.

What is adjacent segregation and what are its different types? When does it occur? In what does it result?

In a reciprocal translocation heterozygote the segregation of a translocated and a normal chromosome together, giving unbalanced gametes with duplications and deficiencies leading to non-viable zygotes. Types: Adjacent 1 - non-homologous centromeres segregate together. (more common) Adjacent 2 - homologous centromeres segregate together (rare)

Why is CO toxic? Mechanism.

In protein complexes such as Myoglobin, CO has 250x the affinity for the heme group than O2. So when you inhale CO, it displaces O2 in the heme and de-oxygenates your body.

Why is antibiotic resistance easily acquired? (in relation to exit channel blocking antibiotics)

In relation to exit channel blockers, it only takes a single nucleotide mutation (in say, rRNA) to alter ribosomal exit channel conformation, rendering the antibiotic useless.

What is 47, XYY called? What are clinical presentations?

Jacobs Syndrome 1) Learning disabilities 2) Speech delays 3) Developmental delays 4) Behavioral and emotional difficulties 5) Autism spectrum disorders 6) Tall stature 7) Occurs in 1/1000 newborn boys

What type of mutation in Fabry can be treated with chaperone based therapy? What does this therapy do? How does this differ from ERT for Fabry?

Missense. Type 1 Binds misfolded enzyme (Alpha-galactosidase A) at active site, stabilizes active site, guides enzyme to lysosomes where it can degrade the aggregated sphingolipid (Gb3). ERT introduces new active enzyme which must be continuously introduced. Chaperone-based therapy assists the cellularly produced mutant alpha-galactosidase A to function properly.

What is Euchromatin?

Lightly packed form of Chromatin. More accessible for transcription. Normally more gene rich.

Describe the role of mitochondria in senescence and some of the mitochondria-related diseases.

Mito damage leads to senesence (lack of cell division) Optic Atrophy - mut in mito fusion machinery Charcot-Marie-Tooth - mut in mito fusion machinery Hereditary spastic paraplegia - mut in mitochondrial protease.

What is the complete mechanism of Sickle Cell and its effects?

Missense mutation in beta globin gene -> Less soluble beta-globin subunit -> Less soluble (mutant) HbA tetramer formed (now called HbS) -> Aggregation of HbS into long fibers -> distortion and increased rigidity of the RBC -> Vaso-occulation of capillaries due to rigid nature of Sickle RBC.

How do immune cells contribute to demyelination? What are the two basic pathways?

Immune cells travel with blood vessel. Can cross the blood-brain barrier, induce inflammatory response and contribute to Myelin degradation via an auto-immune response to myelin itself, degrading it. Th1 - immediate, fast acting inflammatory response Th2 - long acting activation of memory/B-cells for long acting reaction to the myelin. Antibodies.

What are 3 causes for endogenous double strand breaks?

Immune system rearrangements ss breaks - in replication the DNA rep machinery can hit the ss break and cause a ds break Meiosis (recombination)

State the basic principles of electron transport and ATP production in mitochondria.

Mitochondria develop an H+ gradient across their inner membrane then utilize that gradient to fuel a pump (ATP synthase) that adds a phosphate to an ADP. This is why oxygen is important in our bodies. The O2 takes on these H+ from the gradient to form H2O.

How many divisions of genomic elements are there in Mitosis? Meiosis?

Mitosis - 1 Meiosis - 2

Why is p53 called p53?

Molecular weight 53,000 Daltons

Monozygotic and Dizygotic - which is 'identical' and which is 'Fraternal'? What amount of genetic material is shared (common) in each case?

Mono - Identical - 100% same genetic sequence Di - Fraternal - ~ 50% same genetic sequence.

What is a Structural Variant (qualitative hemoglobinopathy)?

Mutations that alter the globin polypeptide properties without affecting its synthesis

What is the node of Ranvier?

Myelin sheath gap. The 1 micron gaps between myelin coated regions of an axon. These areas are non-myelinated. Areas of higher Na+ voltage-gated ion channels.

What is the link between The Epstein-Barr virus and MS?

Myelin surface protein cells look like EBV proteins. As we age our immune cells can not discern as well between pathogens and non-pathogens. If infected with EBV early in life the memory immune cells can more specifically discern between EBV proteins and myelin proteins. If exposed to EBV later in life, immune can mistake myelin cells for EBV proteins -> target myelin cells for immune attack. MS is almost certain to follow.

Structurally, what are the differences between myoglobin and hemoglobin

Myo - single subunit Hemo - tetramer

Define a myofilament and a myofibril and describe the relationship between myofibrils and the sarcoplasmic reticulum.

Myofilament - the actin and myosin filaments in a sarcomere. Myofibril - bundles of myofilaments The myofilaments in the cell are organized into bundles called myofibrils; each myofibril has a "stocking" of SR (sarcoplasmic reticulum) around the bundle and Ca +2 is stored in the SR

What is the most numerous oxygen transporting molecule overall in the human body? Where is it located? What is its oxygen source?

Myoglobin. In muscle tissues. Due to its higher affinity for oxygen myoglobin 'steals' oxygen from hemoglobin that is circulating in the blood stream.

Describe a myosin power stroke

Myosin bound to actin -> binds ATP -> releases actin -> resets head (lever arm) to 'cocked' position -> ATP hydrolyzes -> Myosin rebinds actin -> Pi releases, reinforces myosin/actin binding -> Power stroke -> ADP releases myosin -> Myosin stays bound to actin in rigor conformation.

What is the protein product of DMPK? What does it do?

Myotonic dystrophy protein kinase Essential role in healthy muscle, heart and brain cells.

How many chromosomes total are there in a 3N sample?

N is number of haploid. So in humans - 3N = 69. Triploidy

The poly peptide backbone (once bound) is a repeating sequence of what atoms as read from the N-terminus?

N-C-C

What molecule acts to disassemble coiled SNARE complexes? How does it function?

N-ethymalemide Sensitive Factor (NSF). Hexamer of ATPases. Alpha-SNAP binds NSF, Snare complex goes into center hole of NSF hexamer. Unwinds the SNARE coiled-coil using ATP in the process. Denatures some snare proteins in the process.

What AA mutation occurs in Type 1 Gaucher's?

N370S

What is the pathway for b-adrenergic bronchodialation?

NE binds -> Gs active -> AC -> cAMP -> PKA which blocks smooth muscle contraction.

What is the pathway for b-adrenergic BP increase?

NE binds -> Gs active -> AC stimulated -> cAMP -> PKA -> phosphorylation of contractile proteins, RyR, and Ca channels -> influx of Ca into cytosol from ER/SR and ECF -> increased contractile strength and rate -> increased BP

What type of DNA repair is used to fix all bulges in DNA helix aside from a mismatch?

NER - cos all cause distortions in the DNA

What type of excision repair is used to fix pyrmadine dimers?

NER - cos it distorts the DNA

What gene is affected in NFT1? What protein product does it create? What does it do?

NF1 gene Neurofibromin protein - tumor suppressor

If exogenous DS damage occurs when the cell is in G1 phase, which type of dsDNA repair is used?

NHEJ, because the sister chromatid is not present.

Does the miRISC complex degrade the target mRNA?

NO Perfectly matched or not to target mRNA, the miRISC has endonuclease activity that only cuts mRNA in the middle. Other exonuclease enzymes degrade the mRNA.

Which beta-globin or beta-globin like Hb subunit has a mutated gene in Hispanic Thalassemia? How does this lead to deficiency?

NO Hb genes are mutated. Instead the LCR is deleted. Because the LCR is deleted in this Thalassemia, no downstream Hb expressed. All downstream globins deficient.

Describe the total process of an action potential from initiation back to resting membrane potential.

Na+ influx into neuron -> RAPID Depolarization of the membrane potential to the point of threshold -> At threshold Na+ ion Activation channel gates open -> membrane potential shoots towards the E(Na) -> at E(Na) inactivation gates close (delay) on the Na channels and activation gates open on the K+ channels -> outflow of + K ions drives membrane potential back towards the negative -> Na+ channels completely close and K+ channels close with delay once they hit RMP leading to temporary hyper polarization (refractory) -> Full closure of all K+ channels gets cell back to RMP.

What maintains the cellular charge gradient across the lipid bilayer?

Na, K Pump. 3 Na out, 2 K in. Powered by ATP.

Where is alpha-keratin in the body? What makes it so tough?

Nails, animal horns, hair. alpha-helices cross linked with disulfide bonds.

What blood type is more susceptible for contraction of Cholera?

O

Despite having no smooth muscle, capillaries and post-capillary venules still contract, how is this possible?

Pericytes Relatively unspecialized cells, surrounding capillaries and post-capillary venules that can give rise to smooth muscle cells during vessel growth and wound healing, and may be contractile in nature.

What is an example of covalent enzyme modification?

Phosphorylation. yup, its covalently bound

What enzyme reverses the action of a kinase?

Phosphotase

How can 'hits' occur?

Point mutations - may give oncogene activation (e.g.. RAS or MYC) or tumor suppressor inactivation (e.g.. p53 or pRB) Amplifications and deletions Epigenetic silencing by methylation (eg. CDKN2A) Insertion of a retrovirus containing an oncogene

How is the number of origins utilized in DNA replication regulated? What proteins are involved?

Pre Replication Complex (Pre-RC) - Replication machinery cannot recognize a 'naked' origin. The protein Orc (1-6) must be bound to the origin to mark its location. Orc recruits Cdt1 and Cdc6, these recruit DNA helicase (hexamer, Mcm 2-7)

At 5 weeks what change occurs in hemoglobin subunit production?

Predominant Globin Concentrations Change: Zeta (alpha-like) to Alpha (this remains permanently) Epsilon (beta-like) to Gamma

What cells are considered migrants into the ECM and what do they do?

The cells on the slide as well as macrophages which eat ECM cells, matrix and debris as well as stimulate angiogenesis in the area.

From what are basal bodies derived?

The centrioles

What is a silent mutation? What are its down stream effects in translation?

The codon is changed, but the same amino acid is encoded (mutation in a wobble position). No downstream effect in AA sequence.

Explain how receptor activation leads to signal termination through receptor desensitization and coupling to additional pathways.

Prolonged agonist presence -> receptor itself is phosphorylated by GRK -> recruits b-arrestin -> GPCR inactive, internalized into cell. This reduces the number of GPCR on the surface thereby reducing cellular sensitivity to ligands.

What are two abnormalities of the ear in turner syndrome?

Prominent Auricles - large, visible ears Low Set Auricles - low set ears on head.

Describe a Desmosome

Promote mechanical strength and resist shearing forces. These also use Cadherins

What controls the direction and frequency of transcription?

Promoters (on DNA, upstream of transcription start site)

Where are the promoter and enhancer sequences located? On DNA or RNA?

Promotors - Upstream of the 5' UTR on DNA. Enhancers - can be up or down stream. Transcription factors bind here

In which cell phase (meiosis) does recombination occur?

Prophase of Meiosis I

What is the most common type of cancer in men?

Prostate cancer.

What is the name for a cofactor/coenzyme that is tightly bound to an enzyme?

Prosthetic group

What does N-linked glycosylaiton do?

Protects the protein from aggregating with other hydrophobic proteins that may be hanging around. Hydrophobic aggregation of proteins is a fast way to kill a cell.

Western Blot involves the transfer of what genetic material onto a membrane?

Protein

Are tRNAs only used once or are they recycled?

Recycled.

What is anticipation?

Regarding trinucleotide repeat disorders, The severity and/or onset increasing in subsequent generations.

What polymerase(s) are used in translesion synthesis? Describe the process. Why does this even exist?

Regular DNA poly stalls, changes conformation and recruits: Error prone DNA poly: Pol η (eta) - just adds Adenosine Pol I (iota) - extends the strand (with lots of errors). Very error prone procedure but saves cell from death because this allows the replication machinery to proceed.

What does cholesterol do to the plasma membrane?

Regulation of plasticity. More cholesterol = more rigid, less fluid. Less = less rigid, mor fluidity. ALSO Increases thickness of PM. More Cholesterol = thicker. The PM is thicker than the intercellular membranes. The mole percentage of cholesterol roughly doubles from the ER (7%) to the Golgi (13%) and again from the Golgi to the plasma membrane (26%).

Why is DNA methylation reversible?

So the proper sex-specific imprint may be passed on to progeny. EX: Man's newly formed gamete contains his maternally derived ch1 homologue. Since it came from a female, areas of the ch are female-specific methylated. Male must alter these areas to MALE-specific methylated before passing on haploid gamete for fertilization.

True or False MS patients need to recruit more neurons in the brain to accomplish the same function as a normal patient.

TRUE Due to loss of signal conduction efficiency in axons. This leads to the fatigue observed in MS patients. Constant need for 200-300% the normal neuronal recruitment for normal bodily movement. Pic: top is regular, bottom is MS patient (movement of a single finger)

True or False A mother with a Motichondrial disease will pass that disease on to 100% of her offspring

TRUE Embryonic Mitochondria are ONLY contributed from the ovum, none from the sperm.

True or false Epsilon Globin is more towards 5' end of chromosome 11 than Gamma Globin

TRUE Epsilon expressed first temporally so is more towards 5' end of Chr 11

True or False Former smokers have an increased severity for UC

TRUE Former smokers are at increased risk for UC

True or False GAPs act to switch off Ras

TRUE GAP help hydrolysis of GTP by Ras. GDP bound Ras is inactive.

True or False There is no active transport of water in biology

TRUE H2O always moves via osmotic pressure gradients.

True or False Tetramers of B-globin are present in HbH disease

TRUE HbH - (a-/--). Beta surplus = aggregation.

True or False HbS migrates more towards (+) chg than HbC

TRUE HbS mutation is to Val which is neutral HbC mutation is to Lys which is positive + chg migrate LESS towards + cathode.

True or False Lower pH causes KDEL receptor to bind KDEL-bearing protein.

TRUE Higher (more neutral) pH causes release. Golgi is more acidic.

True or False If you are from a low risk country for MS, but move to a high risk country for MS before the age of 15, you then are at high risk for MS.

TRUE If you relocate before age 15, you adopt the MS risk of the country you move to.

True or false Conduction velocity increases with increasing axon diameter

TRUE Increased surface area of axon increased its conduction velocity.

True or False Hyaluronic Acid is a GAG

TRUE It is NOT a proteoglycan as it is not associated with a protein core. Free GAG.

True or False A ligated integrin blocks apoptotic pathways

TRUE Ligated just means adhered

True or False When cholesterol levels are low SCAP-SREBP complex dissociates from Insig

TRUE Low cholesterol causes SCAP-SREBP to migrate to golgi where bHLH region of SREBP is cleaved and migrated to nucleus to up regulate cholesterol production.

True or False There are originally two pairs of genital ducts in both males and females

TRUE Mesonephric (Wolffian) ducts and the Paramesonephric (Mullerian) ducts are present simultaneously.

True or False Endothelial cells in the lungs do NOT contain special transporters for ions.

TRUE O2 and CO2 pass freely between membranes. No transporters needed.

True or False Ran is the protein that performs its own hydrolization of its bound GTP

TRUE Ran has intrinsic GTPase activity that acts on its self. This GTPase activity is blocked when cargo is bound.

True or False Proper function of the bHLH transcription factor requires cleavage in two different locations

TRUE S1P is luminal, S2P is within the membrane - cleavage by both is required for activation

True or False The nuclear filaments of a Nuclear Pore Complex (NPC) are fused into a basket form.

TRUE The cytoplasmic filaments are free floating and the nuclear filaments are fused into a basket form.

True or False Gonadal development determines secondary sex characteristics.

TRUE The developing gonads being their own regulatory signaling pathways.

True or False The long arm of an acrocentric chromosome contains nearly all of the chromosome's Euchromatin

TRUE The short arm is mostly heterochromatin.

True or False HPFH individuals are clinically normal.

TRUE The up regulation of gamma-globin is a suitable substitute. That is why they are looking at these mechanisms for treating severe b-thalassemias

True or False In myelinated axons, action potentials can only be initiated at nodes of Ranvier

TRUE These are the only site of the voltage gated ion channels. If axon becomes de-mylenated the ion-channels can spread out from these points to cover de-myelinated area.

True or False Disorders associated with the SRY gene can occur in both males and females.

TRUE Though SRY normally comes from the Y-chromosome, aspects of the SRY gene can be transported into an X chromosome thereby affecting females.

True or False You must have a mutation in both NF1 genes to show the complete phenotype of NFT1

TRUE Though it is and AD disease, it is unique in that you need mutations on both alleles for full NFT1 phenotype.

True or False Increasing Zeta globin production in an a-thalassemia patient can benefit the patient.

TRUE Zeta globin is an alpha-like globin. Can act as a substitute.

True or False VHL penetrance is variable in that it increases with age

TRUE by age 65 it is 95% penetrant.

True or False Huntingtons disease is considered an early-onset disease if it is inherited through the father

TRUE later-onset if maternally inherited.

True or False In Alpha thalassemia, Beta globin precipitates

TRUE. Lack of alpha globin results in betaglobin imbalance and precipitation. The inverse is true in beta-thalassemia.

True or False Mutated Fibrillin can inhibit the activity of wild type fibrillin

TRUE. Called the dominant negative effect. Mutated gene product adversely affects the normal, wild-type gene product within the same cell.

True or False The intracellular environment is more acidic than venous blood serum

TRUE. Lower pH = more acidic.

True or False Purines and Pyrimidines are weak bases

TRUE. They are not strong bases.

True or False A non-virilized fetus has female sex characteristics.

TRUE. Virilization refers to the development of male characteristics.

What disease is associated with normal HEXB enzymatic activity and little to no HEXA activity? How can this enzyme be active if the final enzyme product is supposed to be an alpha-beta heterodimer?

TS HEXB homodimer forms the active enzyme

What genes are mutated in TSC

TSC1, TSC2

What are the polar uncharged amino acids?

TSCPNQ The Sleepless Clowns Prefer Ny-Quil Threonine - T Serine - S Cystine - C Proline - P Asparagine - N Glutamine - Q

What enzyme is deficient in Gaucher's disease?

glucocerebrosidase

What sphingolipid builds up in Gaucher's Disease?

glucocerebroside

For some more disease specific flash cards for unit 2..

go here.... https://www.brainscape.com/packs/6631412/invitation?referrer=1664042

What are 2 causes for exogenous double strand breaks?

ionizing radiation medical imaging and treatments.

What is trisomy?

is a type of polysomy (multiple chromosomes) in which there are three instances of a particular chromosome, instead of the normal two.

What is a proteoglycan?

The combination of a core protein and a GAG.

What are the 5 acrocentric chromosomes in the human body?

The human genome includes five acrocentric chromosomes: 13, 14, 15, 21, 22

What is Knudson's two-hit hypothesis?

is the hypothesis that cancer is the result of ACCUMULATED mutations to a cell's DNA. One hit - Premalignancy Two hits - Malignancy Two hits can be on different genes. (tumor supressor (inactivation), oncogene (activator)

How can the body tell the maternal allele apart from the paternal allele?

The methylation patterns on each are different.

What is allelic heterogeneity?

is the phenomenon in which different mutations at the same locus cause a similar phenotype

If a cell contains 300mM of a protein in the ICF and the ECF that the cell is introduced to contains 150mM of NaCl (to which the cell membrane is NOT permeable)...is the solution: Hyper/iso/Hypotonic? Hyper/iso/Hypo-osmotic? And what happens to the cell in terms of volume?

iso-osmotic - the 150mM of NaCl has an osmolarity factor of 2 as that molecule breaks into two particles, each of which is at 150mM which leads to total of 300mM of particles. iso-tonic - no observed effect on cell as external environment is equal in osmolarity. Nothing happens to cell in terms of volume. Isotonic.

What are the characteristics of muscular arteries?

The multiple elastic layers in elastic arteries become only two elastic layers, inner elastic lamina between the intima and the media and an outer elastic lamina between the media and adventitia. Thin endothelial intima. The media is primarily comprised of smooth muscle cells. The adventitia is comparatively thick and contains collagen and elastin.

What is a Nonsense mutation? What are its down stream effects in translation?

The mutation changes the codon from an amino acid encoding one to a stop codon, resulting in a truncated protein. Cuts off all downstream prematurely.

What is HbH? When is it present in the body?

The name of the b-globin tetramer formed in severe a-thalassemia. Present after birth once b-globin is upregulated.

What do the glucose on the end of the N-linked glycosylation added sugar chain denote?

They denote that the protein to which they are adhered is folded properly.

How do osteocytes communicate with one another if they are locked into the bone matrix?

They form gap junctions with one another through small channels in the bone called canaliculi.

Aside from miRNA endonuclease activity, how can they also contribute to mRNA degradation?

They recruit de-capping and de-adenylating proteins to remove protective ends of mRNA transcript.

How do transcriptional activators or repressors affect chromatin conformation? (and subsequently transcription)

They recruit either histone acetyltransferases (HATS) or deacetylases (HDACs). Alter histone/DNA affinity. lose DNA can be accessed and transcribed, tight DNA cannot.

Who is Red Fang?

They're fuc$!ng metal as shit.

In muscle, what protein makes up the thick filament? And the thin filament?

Thick - Bundles of Myosin Thin - Bundles of Actin

What is Hypertrophic Cardiomyopathy (HCM)?

Thickening of the myocardium, without any obvious cause, that inhibits the function of the heart.

In muscle contraction what is the thin filament? What is the thick filament?

Thin - actin filament Thick - myosin filament.

What is the symbol for Psi? And again, what bond is this referring to?

Think of the weapon used by Raphel in the Teenage mutant ninja turtles. Its the C-C bond in the peptide backbone.

What are the two classes of high energy bonds that we need to know? In what molecule (bio) are they found?

Thioester, C-S: AcetylCoA High Energy Phosphate, P-O-P: ATP.

What is the function of ERp57?

Thiol oxidoreductase that allows formation of disulfide bonds. Located in the ER

Describe the molecular basis of skeletal muscle diversity (fast, int, slow fibers) and the value of having this additional complexity.

Three classes: slow, fast, and an intermediate. Each has different myosin isoenzymes, different proportions of mitochondria and oxidative enzymes, different resistance to fatigue, and different speeds of contraction. Slow fibers rely more on oxidative phosphorylation (ATP production in mitochondria) for sustained but slower ATP source Fast fibers rely mainly on glycolytic (rapid glycolysis for rapid ATP production) mechanisms for fast energy Intermediate fibers do both. Complexity gives each muscle additional control and dynamic.

What damage to DNA does UV light normally cause?

Thymine dimer.

What is Heterochromatin?

Tightly packed form of chromatin. Less accessible for transcription. Normally gene poor.

How does chromatin structure affect transcriptional control?

Tightly wound chromatin hide DNA within core, limit access of DNA to transcription factors. Need access to DNA to transcribe.

What is the largest protein in the human body? What does it do?

Titin - coming in at 27K - 33K AAs Travels though myosin thick filament, attaches z-line to z-line via the m-line. Resist tension on the I-band.

What are the relative Tm for dsDNA, DNA/RNA hybrid, and dsRNA?

Tm: dsRNA < DNA/RNA < dsDNA

What is the purpose of an RNA microarray?

To simultaneously see all mRNAs that are being expressed by given cells. Each grid spot on a microarray is a known oligo.

What is the purpose of the t-tubule network?

To transmit the AP rapidly into the depths of the cell that are not in direct contact with the innervating neuron on the surface. AP from the t-tubule network acts to activate (an unknown mechanism) that acts on the SR Ryanodine receptor to release Ca++ from the SR into the intracellular environment, where it can act on the myofibrils.

Describe the process for cellular cholesterol production and signaling.

Transmembrane protein SREBP (located in ER membrane) has a bHLH transcription factor built into its protein chain that regulates both the LDLR and all 30 proteins involved in synthesis. If cellular cholesterol low, SCAP binds SREBP and signals COP2 to form vesicle and take SREBP/SCAP to golgi where cleavage of the bHLH transcription factor occurs. bHLH migrates to the nucleus and up regulates LDLR and all 30 cholesterol synthesis proteins.

What is cadherin?

Transmembrane proteins with extracellular domains that interact with each other, and cytoplasmic tails that bind adapters and actin filaments.

What does an RTK do?

Transmembrane protien, homo-monomers bind ligand, dimerize, auto-phosphorylates using ATP, signals events downstream.

What is the function of NTF2?

Transport RanGDP from cytosol into nucleus

What is the primary difference between Tandem Repeats and Dispersed Repetitive elements?

Transposition. The Dispersed repetitive elements can relocate themselves into other parts of the genome via either a DNA or RNA mediated pathway.

How long is a sarcomere?

Trick question. They change length (from z-line to z-line) based on state of contraction.

What type of ploidy is Trisomy? Triploidy?

Trisomy - Aneuploidy Triploidy - Polyploidy

What are two genetic diseases that we discussed that are largely treatable without correcting genetic abnormality?

Trisomy 21 Metabolic Disorders (Also discussed Phenylketonuria)

What chromosomal abnormality is most commonly associated with down syndrome? What is the common karyotype for the parents of a down syndrome child? What percentage of down syndrome patients have this abnormality as the root cause?

Trisomy 21 (3 copies of chromosome 21) Parents karyotype is normal. 95% of all down syndrome patients have trisomy 21

Just a recap. What are the other names for Trisomy 21 Trisomy 18 Trisomy 13 45, X 47, XXY

Trisomy 21 - Down syndrome Trisomy 18 - Edwards Syndrome Trisomy 13 - Patau Syndrome 45, X - Turner Syndrome 47, XXY - Klienfelters Syndrome

What does the ISCN: 48, XX, +X, +21 signify?

Trisomy of 21 and of X.

In skeletal and cardiac muscle contraction, what binds calcium? What does calcium binding do?

Troponin (NOT Tropomyosin) Troponin binds Ca, undergoes conformational change, moves itself and bound tropomyosin out of the way so myosin can bind actin for contraction.

An example of classic DKA presentation

Trouble catching breath, breathing fast, no other respiratory complaints, intermittent vomiting with no diarrhea, insatiable thirst, looks thin, frequent urine output, family history with intermittent hypothyroidism, dry mucous membranes, fruity odor to breath (rotten apples), long cap refill,

What is a balanced translocation? When does this alter the phenotype? When does it not?

Translocation of a gene from one location to another that results in no loss or gain of genetic material overall. Usually results in no change in phenotype as the gene itself is not interrupted. Can alter phenotype if the translocation happens within an exon, altering its function.

True or False Cadherin stability is Calcium dependent

True

True or False Females are functionally mosaic for their x chromosomes

True

True or False Gaucher's is inherited in an autosomal recessive manner.

True

True or False Generally speaking, homozygotes for a dominant disease are rare as this is normally associated with larger detriment to health.

True

True or False Homozygosity for the Achondroplasia mutation is not compatible with life

True

True or False Premature hearing loss is a symptom of Type 1 OI

True

True or False The mutant p53 is more stable than the WT p53

True

True or False The primers used in DNA replication are composed of RNA

True

True or False On a Turner Syndrome patient the nipples are widely spaced

True

True or False Hypophosphorylated RB inhibits cell entry into s phase

True HYPERphosphorylated RB is turned off (no inhibition). HYPO is turned on (Inhibiton)

True or False Smoking paired with ATD greatly reduces life expectancy

True Lung damage by ATD combined with damaging effects of smoking exacerbate one another.

True or False Robertsonian translocations can result in acentromeric chromosomes and/or double-centromeric chromosomes

True See slide

True or False The terms alternative and adjacent segregation are referring only to the relation of centromere segregation not to total chromosomal segregation.

True Segregation described by the relationship of the centromeres to one another.

True or False An affected child with a rare autosomal recessive disorder has an increased chance of parental consanguinity.

True.

True or False Proteins with similar AA sequences have similar functions

True.

True or False The products of mitosis are diploid

True.

True or False Craniosynostosis is commonly associated with Achrondroplasia

True.

True of False Prenatal diagnosis techniques increase the risk of miscarriage regardless of the method by which the fetal sample is acquired.

True. Both methods increase risk

True or False Type 1 Gaucher's disease is normally a homozygous mutation at N370S

True. Its recessive, so the mutation must be homozygous in order to present.

True or False Turner Syndrome patients are ONLY female

True. The XO genotype develops as female.

True or False Dizygotic twins can be different sexes.

True. Two separate ovum, with two separate sperm.

True or False By definition, a translocation of genetic material must occur between NON-homologous chromosomes

True. by definition, translocations involve genetic exchange between non-homologues.

True or False Structural rearrangements require ds breaks in DNA

True. Inversion, deletion, transposition....all require the ds break in the DNA backbones for mobility.

True or False In mitosis the sister chromatids separate

True. Normal replication/division.

What are the proteases that we discussed that digest any protein?

Trypsin Chymotrypsin Pepsin Submaxillarus Protease

What two substances (that were mentioned) are used to create the visible banding pattern on chromosomes?

Trypsin and DNA dye

What is a specific example of how cleavage can activate an enzyme?

Trypsinogen (inactive digestive enzyme), when cleaved by Enteropeptidase, becomes its active form Trypsin.

Is p53 tummor suppressive or tumor promotional? Is it rendered hyperactive or hypoactive in most cancers?

Tummor suppressive. Involved in promoting apoptosis pathway upon detection of excessive DNA damage. Rendered inactive in most cancers.

What is the function of the VHL protein?

Tumor Suppressor.

What is one way (that we discussed) in which a tumor can resist an immune response to its presence? (think of factors that a tumor cell will express on its surface)

Tumor cells express PDL-1 which binds to the PD1 receptor on the T-cell, signaling that T-cell's inactivation. PDL/PD1 = Programmed death ligand/receptor.

What is a potential issue with biopsy analysis for targeted therapy

Tumor heterogeneity. Different areas of the same tumor can express different mutations. You will treat the tumor with a targeted therapy and only a percentage of the tumor will respond to treatment.

Describe the structure, organization, and function of the basic layers of blood vessel walls.

Tunica Intima - endothelial cells in contact with the blood Tunica Media - elastic laminae, smooth muscle cells, or collagen Tunica Adventicia - outermost. Collagenous tissue and (in larger vessels) a blood vessel network .

What syndrome is 45, X? What are clinical presentations?

Turner Syndrome 1) 99% of fetuses do not survive to term 2) prenatal lymphedema, cystic hygroma 3) webbed neck 4) short stature Postulated that only mosaics survive .

What are two diseases that we discussed that are associated with blue sclera of the eye?

Turner Syndrome Osteogenesis Imperfecta

What is the tetrameric composition of HbF?

Two Alpha subunits and two gamma subunits.

How is it possible to have a normal chromosome number (46) with a trisomy phenotype?

Unbalanced RT between non-homologous acrocentric chromosomes can result in 3 copies of one of the acrocentric chromosome's genetic material. EX: 46, XX, +13, rob(14;13)

What type of alleles/variations is a genetic linkage study useful for?

Uncommon alleles with strong affects.

What are the characteristics of the ciliary membrane?

continuous with the cellular plasma membrane. However, this membrane is compartmentalized (by the transition zone) so that it is a compositionally distinct membrane with unique phospholipids and receptor molecules.

Describe the pathway of insulin release from B-cells via glucose signaling.

extracellular glucose increase -> glucose into B-cell cell -> more ATP produced via glycolysis -> inc [ATP] closes ATP-Sensitive K+ channels -> Depolarization of cell (more toward pos with K+ buildup) -> Voltage-gated Ca channels open -> Ca+ influx -> Ca activation of SNARE proteins -> release of pre-formed insulin from B-cells packaged in secretory vesicles.

Are fibrous and globular proteins mostly soluble or insoluble?

fibrous proteins - typically insoluble; made from a single secondary structure globular proteins - water-soluble globular proteins lipid-soluble membraneous proteins

What are the functions of the following GPCRs? 1) Beta Adrenergic 2) Alpha Adrenergic 3) m2 Muscarinic 4) m3 Muscarinic

1) Bronchodialation and Increased rate/force of heart beat. BP up 2) Vasoconstriction. BP up 3) Opposite of b-adrenergic in heart. BP down 4) Bronchoconstriciton. Just think: both muscarinic receptors oppose actions of the beta-adrenergic. m2: heart, m3: lungs

Where in the body do you find: 1) Hyaline cartilage 2) Fibrocartilage 3) Elastic Cartilage

1) Hyaline - Joint surfaces, articular cartilage, costal cartilage, rings of the trachea and bronchi, framework of larynx, nostrils 2) Fibro - meniscal cartilage, labrum, vertebral discs, discs in symphysis joints, lining of grooves in bones 3) Elastic - found in the external ear, in the epiglottis, and the larynx

What are the 6 types of post translational AA modifications that we discussed?

1) Hydroxylation 2) Carboxylation 3) Glycosylation 4) Acetylation and Methylation 5) Phosphorylation 6) Ubiquitination

If a kcat for a given enzyme is 4000, how many molecules of its substrate can a single enzyme process in 1 second?

4000

What is the normal pCO2 in the human body?

40mmHg

If 9% of an African population is born with a severe form of sickle-cell anemia (ss), what percentage of the population will be more resistant to malaria because they are heterozygous (Ss) for the sickle-cell gene?

42% Answer: 9% =.09 = ss = q2. To find q, simply take the square root of 0.09 to get 0.3. Since p = 1 - 0.3, then p must equal 0.7. 2pq = 2 (0.7 x 0.3) = 0.42 = 42% of the population are heterozygotes (carriers).

What is the karyotype of a patient with Turner Syndrome?

45, X

How much water is in the human body? How much is inside and outside of cells?

45L 27L inside 13L Outside (~5L in other areas)

Who will have more severe Klienfelter's Syndrome phenotypes: 47, XXY or 49, XXXXY?

49, XXXXY. Increasing numbers of sex chromosomes increase severity of Klienfelter's phenotypes.

How much ATP is used by DNA ligase to join both ends of a DNA segment into a plasmid?

4ATP. one per phosphodiester bond. 4 bonds total.

What protein can directly bind and regulate activity of eIF-4E? How does it regulate eIF-4E? What regulates this protein?

4E-BP (4E binding protein) - regulated via phosphorylation status. When not phosphorylated 4E-BP binds eLF-4E and inhibits its cap binding activity (blocks transcription initiation). Phosphorylated = off.

Describe the structure and key features of deoxyribose

5 carbon sugar. Lacks one carbon-bound oxygen. (differ in 2' position from ribose)

Describe the structure and key features of ribose

5 carbon sugar. Oxygen attached to each carbon.

What is the contractile length of a myosin power stroke (single head)

5 nm Also, notes say that TOTAL sarcomere is shortened by 8nm (right, cos 5+5 = 8)

Are either the 5' or 3' UTR involved in translational regulation? If so how?

5' - 40S binds at Kozak then must scan through the 5'UTR into order to find an AUG. The folding/hairpin structures formed by 5' UTR can vary in difficulty to scan through. More difficult scan = less translation overall

Which nitrogenous base, found in humans, gets deaminated to create thymine? What type of mutation does this cause?

5' - methylcytosine Point mutation.

If the DNA template strand reads: 3' GACCTTA 5' How will the RNA transcript read?

5' CUGGAAU 3'

List the differences between a primary transcript mRNA and a mature mRNA.

5' End - - Primary: 5' triphosphate of initial rNTP added - Mature: 7-MeG Cap 3' End - - Primary: Free 3' OH of terminal rNTP in transcript - Mature: Poly AAAA tail (~200nt) Body of RNA - - Primary: Complete transcript, sequence of coding strand of parent DNA (sub U for T) - Mature: Introns removed, exons spliced together.

If the DNA coding strand reads: 3' GACCTTA 5' How will the RNA transcript read?

5' GACCUUA 3'

What are the conserved sequences at the 5' and 3' ends of most introns, utilized in splicing?

5' end - GU 3' end - AG

What is on the 5' end of a primary transcript? the 3' end?

5' end - three phosphates bound to 5' carbon of terminal ribose. 3' end - free 3' hydroxyl bound to 3' carbon of terminal ribose. This is the PRIMARY transcript, not the mature mRNA

At what end of the mRNA in the cytosol is the signal recognition sequence? What does it do?

5' end, first thing translated. This pauses translation and awaits the binding of the Signal Recognition Particle (SRP).

Which end of the primary RNA transcript receives the 7-methylguanosine?

5' end. This is the 5' Cap.

What is the total mechanism of basic cotranslational translocation?

5' signal sequence on mRNA translated -> translation pause recruitment of SRP -> movement to ER -> binding of SRP to SRP receptor lines up 5' nascent protein with closed translocon channel -> GTP hydrolysis by SRP/SRP receptor -> open translocon and continuation of translation -> Signal sequence cleaved by signal peptidase

What is on the 5' end of the PRIMARY mRNA? (pre processing)

5' tri-phosphate.

What percentage of all cancers may be due to heritable high-penetrance mutation?

5-10%

What are all of the Autosomal Recessive Diseases we discussed in unit 2?

5-CCAAPPSSTTG (caps t) 5-alpha reductase deficiency Cystic Fibrosis Congenital Adrenal Hyperplasia AB-Variant of Tay Sachs - GM2AP mutation ATD PKU Pompe Disease Sandhoff Disease Sickle Cell Tay-Sachs Disease Thalassemias (alpha and beta) Gaucher's Disease

Chromosome abnormalities account for what percentage of all first trimester spontaneous abortions?

50%

What is the new mutation rate in Neurofibromatosis type 1 (NFT1)?

50%

What percentage of all cancers have mutations in p53?

50%

Which pathway represents the convergence of many pathways in autophagy?

mTOR pathway.

What are the two ways in which secretory units can be organized? What is meant by simple and compound glands?

Alveolar - bowl or flask-shaped lobules Tubular - organized into tubes Simple - single or few ducts Compound - multiple ducts

What disease is an example of locus heterogeneity?

Alzheimers Disease Mutations in 3 different genes all result in identical clinical presentations.

What is the most common neurodegenerative disease in the USA? What causes it?

Alzheimers Disease. Aggregation of beta-amyloid protein into plaques.

What disease that we discussed are caused by protein aggregation?

Alzheimers, Prion, Parkinsons Amyloidosis - this affects the pancreas.

Describe the structure of collagen

three poly peptide chains join into rigid rope-like triple helix.

What is transcytosis?

transport of materials through epithelial cells via endocytosis on one side and exocytosis on the other.

What is a transposon?

transposons - mobile elements. pieces of DNA that hop around in the genome. Can land in an area and knockout a gene.

What is the Gibbs equation for the amount of energy you can extract from a redox reaction?

∆G'° = -nF∆E'° n = number of electrons transferred. F = Faraday Constant ∆E'° = E'° electron acceptor - E'° electron donor (Rrdox potential)

What is Mendel's First law?

♦ Mendel's First Law: The Law of Segregation. At meiosis, alleles separate (or segregate) from each other such that each gamete (egg or sperm) receives one copy from each allele pair.

What is Mendel's Second law?

♦ Mendel's Second Law: The Law of Independent Assortment. At meiosis, the segregation of each pair of alleles is independent. [Note: genes physically near each other ('linked') on the same chromosome violate this law]

List the 'threats' to Mendelian inheritance patterns.

♦ Penetrance ♦ Expressivity ♦ Sex Influence and Sex Limitation ♦ Environmental factors ♦ Stochastic Effects ♦ Modifier genes ♦ Phenocopies ♦ Pleiotropy

What is gp-41?

A membrane protein of the HIV-1 virus. Forms the anti-parallel a-helix complex for viral membrane binding and fusion.

What is a buffer?

A mixture of a weak acid and a weak base built to resist pH changes with introduction of either acidifying or alkalizing agents.

What is the conserved recognition element within human genes (RNA) that is utilized in 3' poly A tail addition? Where is it located?

AAUAA Located in the 3' UTR

What is the result of Histone Acetylation Histone Methylation And why (mechanism)?

Acetylation - transcription up Methylation - transcription down Histone Acetylation - acetyl group neutralizes + chg of histone, lowers affinity for - chg DNA. Loosens. DNA now more accessible for transcription mechanisms. Histone Methylation - Does not neutralize chg. Recruits silencing or regulatory proteins that bind methylated histones. Transcription repression.

What is the pathway for m2-muscarinic BP decrease?

Ach binds -> Gi active -> AC inhibited -> cAMP down -> closed Ca channels, lower Ca in cytosol -> less frequent and more weak contractions. OR/AND Ach binds -> beta/gamma g-protein cative and binds GIRK -> opens K+ channel -> K+ efflux into ECF -> SA node hyperpolarization -> heart rate slower -> BP down.

What are the percentages of new mutations associated with each of the following diseases? Achondroplasia Neurofibromatosis 1 Tuberous Sclerosis Marfans

Achondroplasia - 80% Neurofibromatosis 1 - 50% Tuberous Sclerosis - 66% Marfans - 25%

What mutated gene and protein are associated with each of the following diseases Achondroplasia Duchennes MD Beckers MD PKU (2 different genetic causes)

Achondroplasia - Gene/Protein: FGFR3 Duchennes MD - Gene/Protein: Dystrophin (DMD) Beckers MD - Gene/Protein: Dystrophin (DMD) PKU - PAH related Gene/Protein: PAH - Cofactor related - Gene/protein: BH4

What are two diseases that we discussed that increase incidence with increasing paternal age at time of conception?

Achondroplasia. MEN2 MEN2B

What are the 4 primary proteins involved in a sarcomere and its structure and regulation? Which are structural and which are regulatory?

Actin - Structural Myosin - Structural (motor) Troponin - regulatory Tropomyosin - regulatory

Describe the process of accommodation? Why does it occur?

Action potential depends on the rapid depolarization of the cell membrane. This is because there is a delay in the opening of the activation gates on the Na+ channel and the closing of the inactivation gates

What is the function of Ran in nuclear transport into the nucleus?

Amphiphilic cargo tranport molecule bind the NLS of a protein trying to transverse the NPC -> guides protein through NPC -> Ran-GTP binds amphilic transport protein -> transport molecule releases protein that it was guiding into nucleus -> Ran/cargo transport travel back out of NPC together -> In cytoplasm Ran-GTP hydrolyzes GTP to release cargo transport molecule.

What is Cas9? How does it work?

An RNA programmable endonuclease. You can give Cas9 a piece of guide RNA which it uses to cut an area of dsDNA

What is a frameshift mutation? What are its downstream effect?

An addition or deletion of a nucleotide in codon. Shifts the entire downstream reading frame

What is a Gaucher Cell?

An affected Macrophage, enlarged and deformed by lysosomal disorder. Lysosome swells and takes up most of cell cytosol.

What is zeta globin? When is it expressed?

An alpha-globin-like protein. Expressed starting with conception, largely diminishes by week 5

What is SPO11? What does it do? When is it active?

An endonuclease that cuts both DNA strands, leaves overhang. Used only in Meiotic HR.

What is a restriction enzyme/endonuclease?

An enzyme that cuts DNA at or near specific recognition nucleotide sequences known as restriction sites. Leaves 'sticky ends' with DNA overhang sequences that can be used to adhere newly introduced DNA.

What ion channel is an example of a primary active transport mechanism?

An example is the Na+ pump, which extrudes Na+ from cells, and requires ATP. Direct usage of ATP = primary active.

What is a prion?

An infectious agent composed entirely of the misfolded conformation of a normal protein in the brain called PrP (prion protein).

Describe the process of chromatin condensation in apoptosis.

An unknown enzyme cuts between nucleosomes in the chromatin chain, breaking the DNA into millions of fragments. These fragments condense more easily than intact DNA chain.

Whats is Aneuploidy?

An-euploid (opposite of euploid = 'not good policy') Incorrect number of chromosomes but not polyploid which is factor increases (2x, 3x...) Aneuploidy Example: Human, 45 chromosomes, 47 chromosomes.

Describe the primary differences between BER, NER, and MMR

BER - repairs non-distorted DNA damage. Base specific removal. removes only one base NER - repairs distorted DNA damage. removes oligonucleotide, (13-30nt). MMR - Repairs close to replication machinery. Fixes DNA pol mistakes. Repairs only daughter strand.

What type of DNA repair is used to fix spontaneous base loss? Deamination?

BER for both - they do not distort DNA

How does Knudson's two hit theory relate to VHL disease?

BOTH copies of the VHL gene need to be knocked out for VHL-related tumors to present.

What are some of the DNA repair proteins utilized in HR?

BRCA1 - tumor suppressor BRCA2 Rad51 - Recruits BRCA2

Which two proteins, involved in the NHEJ/HR repair decision pathway, are in opposition of one another? Which advocates for each of the two repair pathways?

BRCA1 and 53BP1 BRCA1 - Activated more in S/G2 cell phase, so pushes for HR 53BP1 - Activated more in G1 so pushes more for NHEJ

How does BRCA1 relate to resection? How does this regulate the DS repair decision machinery?

BRCA1 recruits resectors. Resection (chewing back of the 5' strand to leave free 3' overhang) is the first step in HR.

Describe the disruption of nucleo-cytoplasmic transport in breast cancer

BRCA2 when mutated can not bind essential binding partners that retain it in the nucleus where it can enact its DNA repair mechanisms. NES on BRCA2 and binding partners more frequently bound and exported from nucleus.

What is Levinthals Paradox? What does it conclude?

Basically that if each protein sampled a wide array of ways in which to fold it would take way to long for proteins to fold in general. They must have a very directed folding pattern that does not sample many different confirmations along the way.

From where does epithelia receive its blood supply?

Basolateral side (even in arteries). Vessels in the underlying CT.

What cells play a large role in inflammation induction in ECM?

Basophils or Mast cells. Important in edema and allergic hypersensitivities. Secretes Histamine and Heparin which are pro-inflammatory and anti-coagulative factors respectively.

Why can CMA testing detect genomic deletions or duplications, but not translocations.

Because CMA is only testing the PRESENCE of a gene and its relative amount. Translocations do not result in an alteration of the amount of a given gene. (except for unbalanced....but she did not address that in class)

Why do DS patients also commonly develop Alzheimers?

Because a gene that predisposes for Alzheimers is located on chromosome 21 (which is commonly trisomy for DS).

Why is there an increased risk of developing liver chirrosis and cancer in ATD?

Because the Alpha 1 AT protein is produced in the liver then transported to lungs via blood. When Glu324Lys mutant Alpha 1AT protein is produced it is misfolded and accumulates in the ER of liver cells -> damage

Why are rare phenotypes such as those associated with autosomal recessive disorders, observed more frequently in inter-familial pedigrees? (incest, there I said it)

Because the chances of reproducing with another person carrying the rare recessive disorder increase greatly.

The chorionic villi are part of the placenta, why can they be used to acquire the genome of the fetus?

Because the chorionic villi arise from the chorion which arises from extraembryonic mesoderm and the two layers of trophoblast that surround the embryo. In other words, the cells of the chorionic villus are derived from the embryo in development. So they are cells with fetal genomes.

Why, if both of the exact same loci (PWS/AS) in Chromosome 15 are 'imprinted' (silenced) is this region essential to have both the paternal and maternal copies for normal function?

Because the imprinting patterns are different from maternal allele to paternal allele. Together the un-imprinted areas of each allele compliment to make a completely functioning loci. If only the maternal allele is present, then only some of the genes are expressed. The rest are imprinted (which are not imprinted on the paternal allele)

Two acrocentric chromosomes's q-arms join at a single centromere forming a balanced product. Why is this balanced if both the p-arms are lost?

Because the p-arms of the acrocentric chromosomes contain rRNA encoding DNA (and satellite DNA). There is so much rRNA encoding DNA in the genome that a loss of these rRNA results in no significant genetic loss.

Why are stereocilia considered large microvilli and not cilia?

Because they contain actin, not microtubules. MTs are representative of cilia.

Why do cancerous cells increase their transport of Glucose?

Because they switch from largely using regular oxidative pathways to using glycolysis and producing lactic acid. This is also why cancers have been described to 'smell funny' (Lactic Acid)

Why was p53 thought to be a oncogene?

Because tumor suppressor genes are supposed to be homozygously mutated in tumors. p53 was heterozygously mutated and still causing cancer phenotypes (later found due to dominant negative effect)

If you need mutations on both NF1 alleles for NFT1 to present, why is it considered dominant?

Because when you have one allele you always develop SOME symptoms (cafe au lait nodules, Lisch nodules..)

Why are the lateral and basal sides of epithelial cells often combined to be called the 'baso-lateral side'?

Because, tight junctions are present at the apical-lateral areas of the epithelial cells leaving the basal and lateral sides of the cells to contain similar components as there are no strong barriers between them. However in some cells the basal and lateral sides can be different.

What are the functions of osteoclasts?

Bone reabsorbing cell 1) Angiogenesis/neurogenesis into bone 2) Reabsorb and remodel bone 3) Upregulate Ca into the bloodstream. (1) they degrade cartilage or bone matrix to allow inward growth of blood vessels during bone formation (discussed below). (2) they function to resorb already made bone to promote remodeling of the bone matrix. (3) They resorb bone for the purpose of mobilizing Ca2+ into the bloodstream (critical for maintaining proper Ca2+ concentrations in blood).

What drug is used to treat Multiple Myeloma by inhibiting proteasome activity?

Bortezomib/Velacade

What is the [H2O] in the ECF/ICF?

Both are 55,000 mM

Which amino acid reside on histones are acetylated in histone regulation? Which are methylated?

Both are K - Lysine.

What are the functions of Arsenic and Cyanide in poisoning the human body?

Both shut down the process by which mito make ATP (The electron transport chain). Severe drop in ATP, death.

What the mechanism of action of Botulism toxin?

Botulism toxin acts to cut SNARE-complex proteins (VAMP2, Syntaxin-1, SNAP-25) on vesicles and other membranes to inhibit vesicle fusion at the neuromuscular junction. Blocks the transmission of neurotransmitters via blocking vesicle fusion. Muscular paralysis. Does not affect other membrane fusions.

What is the most common vector for Cholera transmission?

Brackish water.

Why are fixed, dilated pupils an extremely serious sign of Cerebral Edema?

Brain swelling pinches oculomotor nerve between base of brain and skull. Loss of occulomotor -> loss of pupillary constriction.

How many liters per day flow from the blood into the glomeruli?

180 Liters a day.

Cells after meiosis 1 are diploid are haploid? After Meiosis 2?

After Meiosis 1 - Diploid After Meiosis 2 - Haploid

Describe the two reactions that make the mature 3' end of mRNA's.

After recognition of the AAUAA... 1) Endonuclease rxn - exposes 3'OH closer to the AAUAA sequence (~25bp down stream) 2) Polyadenylate Polymerase Rxn - Only adds As to 3' end. (~200 A)

What syndrome is 45, XO?

Again, Turner Syndrome. Just another way of saying there is only one X, or that there is an X and a gap.

What are the agonists for the b-adrenergic receptor in the heart?

Agonists- Norepinephrine, Epinephrine or Isoproterenol

In an alpha helix, where are the R groups (AA side chains)?

Aimed outward.

Give two examples of drugs that act through modulating different steps in a receptor-G protein-second messenger signaling cascade.

Albuterol - b-agnoist Metaprolol, Propanolol - b-antagonist (blockers) Caffeine - PDE blocker Norepinephrine, Epinephrine - b-agonist Acetylcholine - muscarinic agonist

Which type(s) of VHL are associated with VHL misense mutations?

All Type 2 (A, B, C)

What are structural variations in the genome?

All changes in the genome not due to SNPs.

From which embryonic germ layer do epithelial cells arise?

All of them: endoderm, mesoderm, and ectoderm.

What is the difference between locus and allelic heterogeneity?

Allelic - Different mutations/variations at same locus result in same trait Locus - Different mutations at DIFFERENT loci (even different chromosomes/genes) result in same trait.

There are many different mutations in the PAH gene that can result in the same phenotypic outcome. What is this called?

Allelic Heterogeneity

How many copies of the alpha-globin gene are there per cell? beta?

Alpha - 4 (2 per chromosome) Beta - 2 (1 per chromosome) This is why beta-globin mutations are far more detrimental to b-globin protein levels than a-globin mutations.

What genetic mutation causes Alpha and Beta Thalassemia?

Alpha - Normally deletion of the a-globin gene. Beta - Normally point mutations in b-globin gene, but can be any type of mutation to b-globin.

Which subunit (alpha, beta, gamma) has a GTP bindin domain?

Alpha .

What does ATD stand for?

Alpha 1 - Antitrypsin Deficiency

Which are the two types of secondary structures that we must know?

Alpha helices Beta Sheets

Hemoglobin is composed mostly of alpha-helices or beta-sheets?

Alpha-helices.

Does alternate or adjacent segregation result in a balanced genomic product?

Alternate

Give an example of how alternative poly A sites can be used to make more than one protein from a single gene.

Alternately choosing poly A sites on an mRNA can result in either secreted protein or membrane bound protein.

Where are the R groups (side chains) in beta sheets?

Alternating ~180deg per consecutive AA in angles ~ perpendicular to the plane

What is the action of Alpha 1-AT (AKA SERPINA1) protein?

inhibition of Elastase

What is the function of NXF1/NXT1?

Binds mRNA and rRNA and facilitates export form nucleus through the NPC.

What is the action of n-sec-1?

Binds misfolded/denatured syntaxin-1 after SNARE uncoiling by NSF. Folds syntaxin-1 into primed/inactive conformation (tetramer). However, it stays bound to syntaxin-1, blocking binding/coiling with other SNARE proteins. This is a step in membrane fusion regulation. Specific protein must act on n-sec-1 to remove it before membrane fusion can occur.

What is the function of HSP70?

Binds nacent protein as it is made, allows protein to be completely translated before folding.

What is the function of elF-4E?

Binds the 5' cap. Recruits many other initiation factors. These initiation factors recruit the 40S subunit.

In regards to testing for blood cancers, elevated blasts are observed in peripheral blood. What are blasts? What are relative normal levels for blasts in peripheral blood and bone marrow?

Blasts = Myeloblats (Acute MYELOID Lukemia) - immature white blood cells (unipotent stem cells that differentiate into a class of WBC called Granulocytes). Found in marrow. Normal levels = little to zero in peripheral blood

What does Abiraterone do in regards to PCA treatment?

Blocks CYP 17 activity which blocks the production of testosterone almost completely, regardless of location in the body.

How does cyclosporin work to block immune response?

Blocks Calcineurin phosphatase activity, cannot dephosphorylate NF-AT. NF-AT can then not go into the nucleus (where it would up regulate genes involved in immune response)

What is the function of Gefitinib?

Blocks EGFR kinase activity. Can still dimerize, but does not auto-phosphrylate. No downstream signaling.

What does ipratropium (muscarinic antagonist) do in lungs?

Blocks muscarinic -> bronchodilation.

What does Enzalutamide do in regards to PCA treatment? What is its mechanism of action?

Blocks nuclear translocation, co-activator recruitement, and DNA binding of the AR complex.

What is the function of Cetuximab?

Blocks the EFGR RTK dimerization. Renders inactive.

How does rifampicin function to halt transcription?

Blocks the exit channel in bacterial RNA poly.

What is hemophilia A? What are clinical presentations?

Blood disorder where blood fails to clot appropriately due to a deficiency of Factor VIII Spontaneous bleeds into joints, muscles or intracranial Excessive bruising Prolonged bleeding after injury or incision Delayed wound healing

How is mass spec used to diagnose PKU in newborns?

Blood sample taken, run in mass spec, divides molecules by size (mass), can see peaks in graph for different molecules. Looking for phenylalanine and tyrosine levels in relation to one another. Compare Phe peak to Tyr peak to look for normal/abnormal balance/levels.

Why do people respirate more with metabolic acidosis?

Body trying to get rid of CO2 to reduce H+ conc in body.

What gene is affected in Type 1 OI? On which chromosome it is located?

COL1A1 Chromosome 7

What is the function of carbonic anhydrase?

Catalyze the reaction between CO2 and water into carbonic acid.

Define initiation factor

Initiation factors: proteins needed to initiate ribosome assembly or mRNA translation

In which of the steps of translation does the most regulation occur?

Initiation.

What are two abnormalities of the eye in Turner syndrome patients?

Inner canthal folds - fold of skin covering inner corner of eye ptosis - drooping of eyelid blue sclerae - discolored white part of the eye

Describe the process of collagen production and processing both intracellularly and extracellularly.

Inside Cell: Translocated into the ER then glycosylated/hydroxylated and assembled into triple helix Outside cell: then N and C termini are cleaved off of collagen, collagen can then form into long fibers.

How does the pancreas manage such a rapid release of insulin protein when blood glucose suddenly spikes?

Insulin is pre-made in B-cells and packaged into granules. Granules docked on internal membrane of B-cells with SNARE proteins. When signaled, cell rapidly fuses membranes and releases insulin.

Describe integrin specificity

Integrins bind the ECM as heater dimers. Different heterodimeric combinations can come together to infer specificity to ECM substrate binding.

What are the key class of proteins involved in epithelial cell adherence to the basil lamina?

Integrins.

What are the clinical manifestations of fragile X?

Intellectual disabilities Dysmorphic features: large ears, long face, Macroorchidism - enlarged testes Autistic behavior Social anxiety Hand flapping/biting Aggression

In order for the intron's branch point A to become active for splicing what must first happen?

Interaction with U2 snRNA. Exposes it, makes it reactive.

What is the ISCN?

International System for Human Cytogenetic Nomenclature - The numbering scheme for chromosomes in regards to regions of a single chromosome Numbered from the centromere outwards to the telomeres. Regions and bands (sub group). EX:

What is meant by interstitial and appositional growth?

Interstitial - (growth from within) the new material generated comes from cells within the core matrix of a tissue Appositional - (growth at the surface) the new material generated comes from cells at the surface of the matrix.

What is gene therapy? What are the two delivery methods?

Introduction of DNA (or RNA) molecules into human cells to treat an acquired or inherited disease Ex Vivo - insertion of DNA/RNA occurs outside the patient in cells/tissues which are then given to the patient In Vivo - DNA/RNA constructs injected/delivered directly to the patient

How does cerebral edema occur in DKA?

Introduction of IV fluid will drop osmotic pressure (drop of osmolality) of blood, but will relatively increase the osmolality of the brain. Water crosses the blood/brain barrier towards higher molecular concentration. Swelling.

What is an intron? An Exon? Which are more numerous (take up more space in the transcript)?

Intron - transcribed RNA component of primary transcript. Must be removed before RNA is mature. Exon - transcribed RNA component of primary transcript. cut out and joined together in various sequences to make mature RNA. Introns far more numerous. 'Exons in a sea of Introns'

Hb Kansas has what affect on the hemoglobin? What clinical presentation does this cause?

Lowered O2 Affinity (Locked in Deoxy/lowered affinity state) Cyanosis. Less O2 in RBC

What cell type is only found in blood and connective tissue and can therefore denote connective tissue in histology?

Lymphocytes.

To which AA is Ub added?

Lysine (K)

What is the general AA characteristic of a classic NLS signal?

Lysine (K) and Ariginine (R) rich region ((+) chg rich regions). On surface of protein. Easy to be recognized. Do not have to be continuous. Can be two separate K and R rich regions separated by 10-12 AA.

What AA that we discussed is a target of acetylation and methylation? Where does this occur and in relation to what biological function?

Lysine - the AA in histones that are Acetylated and methylated. Acetylation and de-acetylation of histones (lysines) in gene regulation (HDACs and HATS). In relation to increasing and decreasing DNA/histone affinity - alters DNA availability for transcription.

What type of disease is TS?

Lysosomal Storage disorder.

What is the major Ubiquitin ligase for p53?

MDM2 MDM4 (MDMX) is also present.

Patients with Lynch Syndrome (hereditary nonpolypsis colon cancer syndrome) have defects in which DNA repair pathway?

MMR

Which form of DNA excision repair is used to fix mistakes made by DNA polymerase?

MMR

Which type of DNA repair is coupled to the replication process?

MMR

What are all of the Autosomal Dominant Diseases we discussed in unit 2?

MOM PHARTN! (Farting moms!) +Myotonic Dystrophy 1 Osteogenesis Imperfecta Marfan Syndrome Polycystic Kidney Disease +Huntington's Disease Achondroplasia Retinoblastoma Tuberous Sclerosis Neurofibromatosis Type 1 Trinucleotide repeat disorders = +

Describe cartilage production

MSC and fibroblasts generate chondrocytes at the perichondrium at the cartilage surface. Chondrocytes travel interstitially where they secrete the cartilage ECM which wraps them in a lacunae. Chondrocytes then divide interstitially to make more chondrocytes making more ECM etc....

Describe the cells involved in bone matrix production and their function

MSC produce osteoprogenitor cells which produce osteoblasts which become entrapped in bone matrix and then differentiate into osteocytes. MSC - produce other MSC and osteoprogenitor Osteoprogenitor - produce downstream bone cells. Osteoblasts - Form the bone matrix Osteocytes - Function largely unclear other than signaling through bone matrix.

What are the alkalizing agents in Maalox? And in AlkaSeltzer?

Maalox - Al(OH)3 and Mg(OH)2 AlkaSeltzer - NaHCO3

What types of cells in Gaucher's disease are most affected? (...that contain the lysosomal disorder causing deformation of cell)

Macrophages.

What is 'B-thalassemia major'? and 'minor'?

Major - severe anemia Minor - carrier, clinically normal.

In a prion disease what conformational change occurs in the Prion Protein and what does that cause?

Misfolding! Prion Protein goes from alpha-helix structure (soluble) to alpha-helix/Beta Sheet structure (insoluble). The misfolded Prp is also resistant to proteases (and heat!) so it lingers and (due to insolubility) aggregates.

Can an x-linked recessive disease phenotype present in females? How?

Yes. The properties of x-inactivation. More on this later

What is MCV? What are normal levels? What can low MCV indicate?

Mean Corpuscular Volume - 'Cell size' Normal = 80-100 fl Low - Thalassemia, either alpha or beta.

What does the term 'human lineage specific (HLS)' mean in regards to genomic characteristics? How do they assay for this?

Means the gene has characteristics (length, duplications) that no other species possesses. Occurs on a spectrum, higher HLS is higher specificity to humans genome only. This is assayed for by combining DNA samples from humans and a comparative organism into a single DNA micro array and seeing which species expresses which genes more than the other.

What is personalized medicine in regards to cancer treatment?

Mechanistic blocks that target the specific mutations, or downstream effects of mutations, and treat those specifically. EX Specific - EGFR inhibitor Non-Specific - Chemotherapy

What is leuprolide?

Medicinal Castration!! GnRH analogue. Desensitizes cells to GnRH. Down regulation of FSH and LH leading to hypogonadism -> down regulation of testosterone and estrogen. Fun Fact: Given to sex offenders to lower libido.

Histologically, describe the appearance of neutrophils

Medium dark, multi-lobed nuclei.

What is the function and protein makeup of Helicase in eukaryotes?

Melt/split dsDNA at the replication fork so that DNA Poly can replicate DNA. Makeup - 6 proteins (MCM2-7) in a ring.

What is the function of Ras?

Membrane bound switch, regulated by GAPs and GEFs, that promotes cell growth, survival, motility etc. Common cancer pathway. GTP bound Ras, mutated to stay that way, is constitutively active.

What type of protein is CFTR?

Membrane protein, chloride channel.

What is the difference between a Mendelian trait and a polygenic/multifactorial trait?

Mendelian - one altered gene is sufficient to cause most of the disease phenotype Polygenic - one altered gene is NOT sufficient to cause disease phenotype.

What cells generate chondrocytes?

Mesenchymal stem cells

How does diabetes cause DKA?

Messed up B-cells in pancreas -> Auto immune destruction of B-cells -> Lowered insulin -> Low glucose into cells -> Cells need energy source -> cells break down fat/muscle for energy -> ketones (which are acids) are byproduct of this reaction -> Ketones into blood, increased H+ in blood (DKA) -> Increased respiration to remove H+ Because the cells cannot receive sugar for energy, the body begins to break down fat and muscle for energy. When this happens, ketones, or fatty acids, are produced and enter the bloodstream, causing the chemical imbalance (metabolic acidosis) called diabetic ketoacidosis.

Which joins first in translational initiation: Large subunit of ribosome or Met-Charged tRNA? Is this true for both Prokaryotes and Eukaryotes?

Met-Charged tRNA binds the start codon, then large subunit assembles.

What is the specific AA residue alteration in Hemoglobin Kempsey?

Missense - Asp99Asn

Which classifications of DNA binding domains can form heterodimers?

Zinc Finger Leucine Zipper Helix-loop-helix

What is a Thalassemia?

a form of inherited autosomal recessive blood disorder characterized by abnormal formation of hemoglobin.[1] The abnormal hemoglobin formed results in improper oxygen transport and destruction of red blood cells.[1]

What is a proband?

a person serving as the starting point for the genetic study of a family

What is the osmolarity for a 1M solution of NaCl?

2 osM 2 solute particles/molecule dissolved. Osmolarity depends on the number of particles present in solution.

What is the threshold of GM2 accumulation amount normally associated with TS?

>300x (or up to 300x) over normal amounts.

Why does the DNA polymerase enzyme not denature at the high temperatures used in PCR?

It is a specific DNA poly from a thermophilic bacteria. Can survive at high temps.

What type of mutation causes sickle cell disease (SCD)?

Missense - Glu -> Val in the beta globin gene on Chr 11. Decreases solubility.

What type of mutation is most common in p53?

Missense in the DNA binding domain.

What are the three most commonly used types of DNA polymorphisms as tools for finding genes?

Microsatellites Single-Nucleotide-Polymorphisms (SNPs) Copy-Number-Variants (CNVs)

What are cilia and what are the three types?

Microtubule containing protrusions on the apical sides of epithelial cells that serve a variety of functions 1) Primary Cilium 2) Motile Cilium 3) Sensory Cilium

Which population is more commonly affected by PKU?

Northern European

Which population is more commonly affected by ATD?

Northern European Caucasians

What is the hygiene hypothesis about MS that correlates with the MS pattern in developed countries?

Not enough exposure to pathogens/parasites early in life leads to weaker immune system. Cleaner countries build weaker bodily defense systems.

What is a barrier nup?

Nucleoporin - are a family of proteins which are the constituent building blocks of the nuclear pore complex. Barrier nups are involved in regulation of what is able to pass through the NPC.

What is a nucleoside? Nucleotide?

Nucleoside = Nitrogenous base and 5-carbon sugar Nucleotide = Nitrogenous base, 5-carbon sugar, and a phosphate group

How do AZT and DDI work to halt DNA replication?

Nucleoside Analogues. Chain terminators (AZT shown). Look like nucleotides but don't have the free 3' oxygen to continue the chain. Halt DNA replication.

Is Deoxyadenosine a nucleotide or a nucleoside?

Nucleoside. No mention of phosphate. Nucleotide = deoxyadenosine monophosphate.

What is the complete molecular mechanism of Achondroplasia?

Point mutation at nt1138 on Chr 4 -> Misense mutation Gly380Arg -> GOF mutation of FGFR3 protein -> Increased inhibition of ossification

What are small silencing RNAs? What are three examples of these?

Small RNAs (<200nt) that act in repression of gene expression via various methods. EX: 1) siRNA 2) miRNA 3) piRNA

What class and size of AA are strong helix formers?

Small hydrophobic AA such as Ala or Leu

What are the clinical features of Achondroplasia?

Small stature Rhizomelic (Proximal limb, attached to hip and shoulder) shortening Genu Varum Short Fingers Large Head, frontal bossing Midfacial retrusion Small foramen magnum, cranio cervical instability

Histologically, describe the appearance of lymphocytes

Small, dense, dark single nuclei. Marked with an L in pic.

What is another name for the leading edge of a cell in motion? What actin related protein is active here?

lamellipodium Arp2/3

What type of alleles/variations is a candidate gene study useful for?

powerful for common risk alleles with small to moderate effects

What is an aliphatic amino acid?

side chain of AA has carbons linked in open conformation (not into a ring like an aromatic sidechain)

What is HbH disease? What is its genotype and effect?

α-thal-1/α-thal-2 (- -/a -) = About 5-30% of their hemoglobin is β4 (HbH), which precipitates.

What are the typical clinical features of CF?

* Chronic sinus infections, * Nasal polyps * Recurrent respiratory infections * Bronchiectasis * Exocrine pancreatic insufficiency

What is 47, XX, +18 called? What clinical presentations?

- Edwards syndrome (trisomy 18) Small for gestational age, small head, clenched fingers, rocker-bottom feet. Nearly 100% lethal by the first month.

What hematocrit level constitutes polycythemia? What is normal?

>55% - Polycythemia Normal = 38.8 to 50% for men 34.9 to 44.5% for women. The normal range for children 15 years of age and younger varies by age and sex.

In diagnosing Marfans syndrome, what systemic score denotes a positive diagnosis?

>7

What does a hypertonic solution in the ECF do to a cell?

Causes cell to shrink. Hyper and hypotonic refer ONLY to the observed physical effect on the cell. Hyper = shrink the cell Hypo = swell the cell.

What is the name for the syndrome associated with a duplication at 22q11?

Cay Eye Syndrome

What are CNVs? What percent of the genome do they cover?

Copy Number Variations - the bulk of all structural variations in the genome. These include insertions, deletions, and duplications. 12% of the whole genome.

What is a basal body and what is its function?

Core anchors from which cilia are formed. Microtubule rich cylinder shaped structures formed from nine triplet microtubules

What DNA polymerase(s) has 5' -> 3' exonuclease activity?

DNA poly I. Exonuclease activity in the 5'->3' direction. removal of the RNA primer in DNA replication.

Which enzyme removes the RNA primer placed by DNA primase for initiation of DNA replication?

DNA polymerase I.

Recombinant events in pericentrically inverted chromosomes can result in what in regards to the long and short arm.

Deletion of some short arm material and duplication of some long arm material.

What hormone from the testes signals the proper formation of the penis, the scrotum, and the proper location of the urethral opening at the tip of the penis?

Dihydrotestosterone. (DHT)

What happens to RTK when ligand binds?

Dimerization. Activation of receptor tyrosine kinases depends on dimerization.

Hb Kempsey has higher O2 affinity. What does this cause?

Diminished O2 release to tissues (locked in Oxy affinitive state). Body responds by making more RBC. Overproduction -> Polycythemia.

What are the typical clinical manifestations of mitochondrial diseases?

Dysfunction of the respiratory chain These disorders tend to affect tissues that heavily rely on oxidative phosphorylation (brain, retina, skeletal muscle and heart)

What is the largest human gene?

Dystrophin - DMD

In regards to 5' capping and 3' poly AAA addition in prokaryotes, describe the process and the differences between the eukaryotic and prokaryotic process.

Prokaryotic mRNAs don't get 5' caps or 3' Poly AAA tails.

Again, which AA are most commonly found in loops/turns and why?

Proline - AA conformation locks peptide backbone in to tight turn (usually in position 2) Glycine - lack of sidechain makes it very flexible (usually in position 3)

Which two AA are common in beta turns? Why?

Proline - AA conformation locks peptide backbone in to tight turn (usually in position 2) Glycine - lack of sidechain makes it very flexible (usually in position 3)

How can you tell L from D isomer?

"CORN" - COOH, R(sidechain), NH2 in 3D, Center the carbon atom, project hydrogen atom away into screen. If the Carboxyl, sidechain, and Amine group reads 'corn' counter clockwise its L isomer. If clockwise its D isomer. See pic to clarify.

What is a run of homozygosity (ROH)? What can it indicate?

"Runs of homozygosity" or ROH are regions of the genome where the copies inherited from parents are identical. Any ROH greater than 5% of entire genome are reported. This implies that with high ROH that the mother and father are most likely related. This higher the ROH the more closely related (mostly)

How is this ISCN location read? 13q13.6

"The thirteenth chromosome in the q one three point six position"

What is consanguinity?

"blood relation", (from the Latin consanguinitas) is the property of being from the same kinship as another person.

What is the direct method for calculating mutation rates?

# of NEW mutations / # of ALLELES in the population Autosomal dominant conditions with 100% penetrance one can simply count the number of new cases that occur with no family history. For example, if 12 disease cases are identified in 100,000 children and 10 of the 12 cases have a negative family history, then the mutation rate is 10/100,000 children. Since each child actually as 2 alleles for each gene the theoretical gene 'mutation-rate' (μ) is 10/200,000, or 1/20,000 alleles.

What is euploid?

'Good polidy' - EX: humans - 46 chromosomes.

What is polyploid?

'many ploidy' - 3x(haploid), 4x(haploid).. factor increases of chromosomes . EX: Humans - 69, 92... chromosomes

What are the five steps in transcription that are shared between prokaryotes and eukaryotes?

(1-3) Initiation - 1) Recognition/binding DNA - 2) Isomerization, forms transcription bubble - 3) Binding of first two rNTPs 4) Elongation - production of RNA transcript moving in 3'->5' direction on DNA. 5) Termination - stop site, RNA poly dissociates from DNA.

Which end of an MT is towards the synapse of axons? (distal end) Therefore which motor protein takes cargo to the distal ends of axons?

+ end towards synapses/distal axon. So Kinesin takes cargo to distal ends of axon.

If the trans-epitheal potential is -60mV (with respect to the apical side) and the Vm(BL) is -40mV, what is the Vm(AP)?

+20mV V values are always the value of the potential of the inside of the cell relative to the outside. Blood is 0, going from blood to cell you go down 40 (BL)

What is Trisomy 13 Called? What clinical presentations?

- Patau syndrome Characteristic faces, severe intellectual disabilities Congenital malformations - holoprosencephaly, facial clefts, polydactyly, renal anomalies. More than 80% of children with Patau syndrome die within the first year of life. Children with the mosaic variation are usually affected to a lesser extent.

What factors can influence a patient's perception of risk in genetic disorders/counseling?

- Preexisting assumption about level of risk - Personal experiences with condition - Attitudes about illness/disabilities - Anticipated burden of having the disease or raising a - child with a disease - Temporal factors - times change how people view their situation - Gender

If the basolateral Vm = -70mV and the Apical Vm = -10mV What is the transepitheleal membrane potential

-60mv The membrane potential is always measuring the potential of the inside of the cell relative to the outside. Vm(BL) goes neg 70 (from blood at 0) into cell, leaving cell into apical space must go positive 10mV (due to -10mV drop from AP space into cell)

What is the voltage difference across the ER/SR into the cytosol?

0

How many proteins constitute DNA pol I in E.Coli?

1

On which chromosome is the gene for glucocerebrosidase?

1

What energy is used by the heat shock protein class in its effort to refold a single protein? Describe process.

1 ATP - ATP binding opens heatshock protein and allows properly folded protein to leave and misfolded protein to enter. ATP hydrolysis closes HSP and allows protein to fold. So ATP = open, exchange of proteins ADP = closed, protein folding.

How many ATP are used to charge a tRNA with an AA?

1 ATP - yes, you have heard that there are two high energy bonds, but ATP -> AMP in this reaction so the high energy bonds of ATP AND ADP are utilized.

How many GTP are used in the complete Ran-mediated transport of one protein into or out of the nucleus

1 GTP.

In regards to SNPs, how often do they occur between two individuals? Percentage wise how different/similar are humans in that regard? What is the ballpark number of total SNPs between two individuals?

1 SNP per 1000 bp between any two individuals We are 99.9% identical There are ~ 3,000,000 SNP between any two individuals

What is the frequency of Huntingtons disease?

1 in 10000 births

What is the carrier frequency for type 1 Gaucher's in Ashkenazi Jews?

1 in 15.

What is the frequency of fragile X per sex?

1 in 2500-4000 males 1 in 7000-8000 females

What is the frequency of Osteogenesis Imperfecta?

1 in 30k - 50k births.

What is the frequency of hemophilia A?

1 in 4000 male births.

What is the frequency of Tuberous Sclerosis?

1 in 6000 births

What percentage of lung cancers are due to mutations in: 1) Epidermal Growth Factor Receptor (EGFR) 2) Anaplastic Lymphoma Kinase Receptor (ALK) 3) KRAS

1) 17% 2) 8% 3) 25%

Describe features that may complicate the assessment of an autosomal dominant pedigree.

1) AD = wider range of clinical presentations than AR. 2) Penetrance more of an issue 3) Variable Expressivity 4) Genocopy: A mutation in a different gene causing the same syndrome. 5) Phenocopy: A syndrome caused by environmental factors that mimics a genetic disease.

Describe the mechanisms of resistance to traditional endocrine therapy for prostate cancer

1) AR activation via non-gonadal testosterone (cancer cells make their own) 2) Overexpression of AR in cancer cells 3) AR mutation leading to promiscuous AR activation. 4) Truncation of AR, leads to constitutively active ligand binding domain.

What energetic molecule is bound/used by: 1) Kinesin 2) Dynein 3) Tubulin 4) Actin 5) Intermediate Filaments

1) ATP 2) ATP 3) GTP 4) ATP 5) None used in assembly

What is the purpose of the gel matrix formed by GAGs?

1) Allow active diffusion of small metabolites but block the movement of large structures such as bacteria. Function as selective sieves 2) Creates a high swelling (turgor) pressure that allows the ECM to resist large compression forces. Consider the value of this for the cartilage in your knee joints.

What are the three ways in which repressors can inhibit transcription?

1) Bind DNA directly, inhibit Activator binding 2) Inhibit bound activators 3) Inhibit basal (general) transcription factors

Via which two pathways does MDM2 inhibit p53?

1) Blocking activation domain of p53, no binding of cofactors allowed by p53 protein. No function 2) Acts as ubiquitin ligase, marks p53 for degradation via proteasome pathway.

Why are K+ levels abnormal in DT1?

1) Body must reabsorb Na from filtrate in kidneys. Exchanges K+ for charge balance. K+ lost into urine. 2) Inc H+ in extracellular environment, cells uptake and exchange K+ for charge balance. Cells lose K+

Describe the routes by which 1) extracellular Ca2+ enters the cytoplasm 2) Ca2+ moves out of the ER/SR into the cytoplasm

1) Ca in to cytoplasm. - Voltage/ligand gated channels, ion channels 2) IP3 and RyR receptors 3)

With are the three major ways in which most pre-mRNA's are processed (eukaryotes)?

1) Capping 2) Splicing 3) Cleavage/Polyadenylation.

Why is Ca signaling so rapid when compared to other signaling/messaging factors?

1) Cellular [Ca++] is very low compared to the ECF. Influx is extremely rapid 2) Does not involve an enzymatic intermediate (ex: kinase) which requires activation and degradation for on/off signaling. Ca up is a signal, Ca down is the opposite signal

What does a small interfering RNA do?

1) Cleavage of mRNAs 2) Transcriptional silencing/heterochromatin formation 3) Mobile element (transposons,etc.) silencing (germline,gametogenesis,etc.)

What is the function of the coat proteins?

1) Coat and form vesicles (bends the membrane into sphere) 2) Target vesicles to the right place 3) Ensure that the right membrane proteins get associated with that vesicle (because they can sense what is inside the vesicle)

Of the AD disease we discussed which display: 1) Complete penetrance 2) Incomplete penetrance 3) Variable Expressivity 4) Locus Heterogeneity

1) Complete Penetrance - Achondroplasia, Tuberis Sclerosis 2) Inc Penetrance - Retinoblastoma 3) Variable Exp - Neurofibromatosis type 1, Tuberous Sclerosis, Osteogenesis Imperfecta Type 1, Marfan 4) Locus Heterogeneity - Tuberous Sclerosis

Why are cilia good for signaling?

1) Concentrates signal using high receptor surface to volume ratio, 2) The signal is localized and polarized within discrete domains of the cell 3) The receptors are positioned away from interfering cellular domains 4) The cilium can function as a mechanical detector of flow.

Describe the two domains of a sequence specific DNA binding protein

1) DNA bindin domain - confer sequence specificity (4 categories) 2) Activation domains - regulate protein-protein interaction. recruit general transcription machinery and/or co-factors.

What are the two basis categories for elements that control gene expression (transcriptional)? What are examples of each? What are each of their classification (Cis/Trans)?

1) DNA control elements - Part of the DNA sequence that acts locally upon itself. EX: Promoter proximal element, TATA box, enhancer. Cis - acts on self 2) Transcriptional activators/repressors - proteins encoded by one gene that act on other genes to regulate their transcription. EX: General transcription factors. Trans - encoded by other gene, act on this gene.

Describe the process of NHEJ

1) DS break recognized and bound by Ku 2) Ku recruits DNA-Pkcs (DNA protein kinase) 3) DNA-PKcs recruits Artemis 4) Artemis processes broken ends 5) DNA polymerase creates sDNA where lacking 6) Ligase IV seals it all together.

What are the four main characteristics of epigenetic phenomena?

1) Differing gene expression pattern, identical genome 2) Inheritance through cell division, even through generations 3) Like a switch: ON/OFF 4) Changes are erasable, convertible, maintain plasticity

How do you diagnose Acute Hyperkalemia?

1) EKG, arrythmias 2) Serum K+

What is the name for the epithelial cells that: 1) Contact the blood and lymph 2) Line internal cavities of the body.

1) Endothelium - blood and lymph 2) Mesothelium - internal cavities.

What are the acquired capabilities of cancer cells?

1) Evasion of apoptosis 2) Self-sufficiency in growth signals 3) Insensitivity to anti-growth signals 4) Sustained angiogenesis 5) Immortality 6) Tissue invasion and metastasis.

Describe the process of sanger sequencing

1) Events in the pic 2) run the 4 samples on the same gel and read off the sequence from the bottom up (5'->3')

What are the characteristics of large diameter axons?

1) Fast CV 2) Low threshold to stimulus 3) Higher safety factor 4) Myelinated

Describe fibrillar collagen, fibril-associated collagen, and network forming collagen, their assembly and function.

1) Fibrillar collagen: assemble in large bundles, called fibrils. These rope-like structures can have great strength to resist tensile stresses in tissues. Collagen Type I is an abundant component of fibrillar collagen.] 2) Fibril-associated collagen: on surfaces of collagen fibrils. Are thought to link collagen fibrils to each other, or to link collage fibrils to other tissue components. 3) Network-forming collagen: very thin fibers assemble into interlaced networks that form porous sheets. Collagen Type IV is a common component of the network-forming sheets in basal laminae.

What are the three steps of tissue preparation for histological study?

1) Fixation 2) Slicing 3) Dying

What are the protein separation/purification/identification methods that we discussed and what do they separate protein based on?

1) Gel Filtration Chromatography - size 2) Ion Exchange Chromatography - charge 3) Affinity Chromatography - ligand binding properties 4) Gel Electrophoreisis/SDS - charge/size coupled 5) Mass Spectometry - mass determination 6) Western Blot - identification, based on mass.

Define the four major classes of ECM components and their properties.

1) Glucosaminoglycans (GAGs)- Main component of ECM. unbranched polysaccharide chains composed of disaccharide repeats. Can become highly hydrated, form gel matrix, structural support. - Proteoglycans (PGs) - PGs are covalently linked complexes of GAGs and protein. Combination of the sugar chain and a protein. 2) Fibrous Proteins - Collagen and Elastin. Scaffolding proteins. Collagen is most abundant protein in the body. 3) Multidomain Adapter Proteins - Fibronectin and Laminin.

What are the reproductive options currently available for couples with increased risk for having a child with a genetic disorder?

1) Have children via traditional means, no testing. Accept risks 2) Choose not to have children 3) Adoption 4) Prenatal diagnosis, with or without termination of affected pregnancy 5) Sperm sorting 6) Sperm/Egg Donor 7) In Vitro Fertilization (IVF) with surrogate to carry pregnancy. 8) Pre-implantation genetic diagnoses.

What are the two classes of chaperones?

1) Heat Shock 2) Chaperonin

Describe the two major mechanisms for how skeletal muscle tension is graded and regulated.

1) Increase/decrease frequency of action potentials. 2) Recruit varying number of motor units

What are the three steps of transcription?

1) Initiation 2) Elongation 3) Termination

Identify the important differences between bacterial and eukaryotic translational initiation.

1) Initiation recognition sequences - Prokaryotes - Shine-Delgarno - Eukaryotes - Kozak 2) Initiation Proteins - Prokaryotes: IF1, IF2, IF3 - Eukaryotes: eIF-4E, eIF-4G, eIF-3, eIF-2, eIF-4A 3) Location of AUG - Prokaryotes: Binding of Shine-Delgarno/AntiShine Delgarno locates AUG directly to P site - Eukaryotes: Ribosome (40S) binds Kozak, scans in the 3' -> 5' direction looking for an AUG.

Describe the process of producing insulin in E.Coli

1) Intro of insulin mRNA to a reverse transcriptase, produce cDNA 2) Cut a plasmid and the cDNA with restriction enzymes, -> sticky ends 3) Insert cDNA into plasmid genome. 4) Transform plasmid into e.coli cells. 5) Use plasmid antibiotic resistance to wipe out all e.coli that did NOT uptake plasmid 6) Run gel of different proliferated E.Coli colonies. Determine which colonies took up the cDNA insertion based on length. 7) Heavily proliferate the cells that DID take up the plasmid AND that have the protein. 8) Purify protein.

What are the A, I, and H bands in a sarcomere? What is the M-line?

A - The visible thick filament, dark (The length of the myosin) I - The visible light area between thick filaments (Actin w/o myosin) H - The gap between actin filaments M-Line - Mid point of thick filament.

List the three mechanisms that different cells have evolved to keep from swelling and bursting.

1) Membrane impermeable to water 2) Cell wall to physically restrain volume of cell - (plants, bacteria...) 3) Osmotic balance in and out.

What is occurring if the equilibrium potential is not equal to the actual membrane potential? Vm (does not equal) E

1) Membrane is impermeable to ion of interest 2) There is an active membrane pump maintaining difference in potential.

Which microfilament make up: 1) Cilia 2) Microvilli

1) Microtubules 2) Actin filaments

How does the GroEL/GroES protein function? How much energy is used and in what form?

1) Misfolded protein enters open side, binds walls of GroEL 2) GroES binds same side to cap off, contributes ATP to overall structure (this causes opposite side cap to release. 3) ATP hydrolysis causes misfolded protein to release from walls of GroEL, fold on its own. 4) Opposite side cap binds, releases cap so folded protein can leave.

What are two of the ways in which you can lose heterozygosity?

1) Missegregation in mitosis - the sister chromatids travel together instead of the homologous chromosomes. 2) HR (followed by segregation) that results in homologous pairs of chromosomes having same genetic regions.

What does a piRNA do?

1) Mobile element (transposons,etc.) silencing (germline,gametogenesis,etc.) 2) Transcriptional repression

What are the three key features of a good plasmid vector

1) Origin of replication 2) Restriction sites 3) Antibiotic resistance.

What are the assumptions of the Hardy-Weinberg equation? (Without which the equation does not work)

1) Population is large and matings are random 2) Allele frequencies remain constant over time because - No appreciable rate of new mutation - No selection for/against any allele - No appreciable immigration/emigration of persons from population with different allele frequencies

What are the two proteins that guide the initiator tRNA into the P-site in 1) Prokaryotes and 2) Eukaryotes? Which of these is bound to GTP? What is that GTP used for?

1) Prokaryotes - IF2 2) Eukaryotes - eIF2 Both are GTP bound. GTP hydrolysis when initiator tRNA is properly placed in A site, GTP hydrolysis and departure of IF2/eLF2.

What are the primary functions (reasons) for epithelial cell polarity?

1) Unidirectional secretion and/or absorption of molecules to or from one side of the epithelium 2) Transepithelial transport of ions and macromolecules from the apical to basal surfaces (or visa versa) 3) Transcytosis 4) Localizing and orienting intercellular signaling either among epithelial cells, or between epithelial cells and other cell types

What four things make up the ground substance?

1) Proteoglycans 2) Other secreted proteins/glycoproteins 3) Inorganic and Small solutes. 4) Water

What are the general characteristics of ciliopathies?

1) Rare 2) Pleiotropic 3) Overlapping 4) Structural 5) Diverse 6) Genetically complex. Rare. On average, the incidence is approximately 1:100,000. While each syndrome is rare the combined incidence of ciliopathies may be more prevalent and similar syndromes may be combined. Pleiotropic. Each ciliopathy is characterized by different clinical outcomes. Overlapping. Most of the ciliopathies have overlapping phenotypes and genetic mutations. Structural. Mutations often affect core cilium structure and function. Diverse. ~50 genes are known to be mutated in ciliopathies to date. Genetically complex. Mutations in the same gene (Cep290) can produce four different clinical outcomes suggesting that second site modifier mutations and genetic background is important to the clinical manifestations of ciliopathies.

What are the 5 steps common to all excision repair pathways?

1) Recognition 2) Endonuclease - cut of backbone flanking damaged/mismatched nt 3) Nuclease - removal of damaged DNA fragment 4) DNA Polymerase - replace removed DNA with new 5) DNA Ligase - seal remaining nick in phosphodiester backbone

Describe the complete steps of NER

1) Recognition 2) Local unwinding of the DNA duplex 3) Double incision of the damaged strand (endonuclease) 4) Filling gap with DNA Poly 5) rejoin ends by DNA ligase

Describe the complete steps of BER

1) Recognition of non distorted, mismatched site 2) Removal of base by DNA glycosylase 3) Cut of 5' side of AP site by APEI endonuclease 4) Cut of 3' side of AP side by AP lyase (part of DNA pol ß) 5) Repair of excised site by DNA pol ß and DNA ligase.

What are the three steps of transcription initiation?

1) Recognition/binding 2) Melting open DNA duplex 3) Two initial rNTPs created

What are the common anti-hormonal treatments for PCA?

1) Removal of gonads - either via bilateral orchiectomy or medicinal castration. 2) Block androgen receptor via Rx.

What are the 4 fundamental ethical principles behind genetic counseling?

1) Respect for patient autonomy 2) Beneficence - personal well being is promoted 3) Nonmaleficence - need to do no harm 4) Justice - includes equity with provision of equal care

What are two important characteristics of ion channels?

1) Selective - only specific ions 2) Gated - only passes ions when gates are open ('voltage gated ion channels')

List the two classes of activators and repressors. Define

1) Sequence-specific DNA binding proteins - bind directly to promotor or enhancer elements in DNA. 2) Cofactors - Do NOT bind directly to DNA, bind the Seq Specific DNA binding proteins.

What are the three types of skeletal muscle fibers and where are they found in the body? What is their function?

1) Slow - sustained contractions. Muscles for posture 2) Intermediate - Mix of slow and fast. Found in many places 3) Fast - Rapid bursts, sprinting, jumping. Most muscles contain all three types of fibers.

What are the characteristics of Replication origins in DNA?

1) Unique DNA segments, multiple short repeats 2) Recognized by origin-binding proteins 3) Rich in A=T pairs. (easier to melt apart)

What are the three active sites within the ribosome? (the site of polypeptide synthesis)

A - aminoacyl site P - peptidyl site E - exit site

List the functions of the 5' cap of the mRNA

1) Stabilization of RNA transcript (protect form exonuclease) 2) Binding site for regulatory proteins -> nucleic and cytoplasmic functions 3) Export from nucleus 4) Degradation control - removal of cap 5) Translational control

Give examples of antibiotics that work by affecting translation by either: 1) Targeting the Ribosome 2) Inhibiting translation initiation

1) Streptomycin, Erythromycin, Tetracycline, Chloramphenicol (highlighted in slides) 2) Rapamycin (via m-TOR pathway (m-TOR deactivates 4E-BP allowing

What are the postulated benefits of swelling at the site of a wound?

1) Structural support - swelling immobilizes injured area. 2) Increased capillary permeability and ground substance increase diffusion of molecules and nutrients in swollen area.

What are the major functions of the ER?

1) Synthesis of lipids (phospholipid, ceramide, and cholesterol) 2) Control of cholesterol homeostasis (cholesterol sensor and synthesis) 3) Ca+2 storage (rapid uptake and release) 4) Synthesis of proteins on membrane bound ribosomes 1. Co-translational folding of proteins and early post- translational modifications. 2. Post-translational insertion into the membrane Quality Control

True or False 1) Ca pumps use ATP to move Ca++ against its concentration gradient 2) Na/Ca exchangers also use ATP in the process of exchanging Na for Ca across the plasma membrane

1) TRUE 2) FALSE

True or False 1) Smooth muscle contains no troponin 2) Calcium regulates contraction in smooth muscle

1) TRUE 2) TRUE

The phenotype of malignant or cancer cells is that the cells are:

1) Unresponsive 2) De-Diferentiated 3) Invasive 4) Metastatic 5) Clonal a. Unresponsive to normal signals for proliferation control. b. De-differentiated, that is, lack many of the specialized structures and functions of the tissue in which they grow. c. Invasive, that is capable of outgrowth into neighboring normal tissues to extend the boundaries of the tumor. d. Metastatic, that is capable of shedding cells that can drift through the circulatory system and proliferate at other sites in the body. e. Clonal in origin, that is, they are derived from a single cell.

What is a mechanism by which smooth muscle resist fatigue?

Smooth muscle can remain in the state where myosin and actin remain bound and locked in a contracted state without consuming ATP. Can lock into contraction.

What are the two general aspects of epithelial cell polarity?

1) The plasma membrane of each epithelial cell (owing to tight junctions) is segregated into different areas. 2) Owing to cytoskeletal arrangement, the cytoplasm of the cell itself is polarized.

How do protein-DNA interactions contribute to transcriptional control?

1) Transcription factors/DNA - activation or repression. 2) Histone modifiers - Histone/DNA affinity. 3) DNA dependent ATPase - Histone movement

What does a micro RNA do?

1) Translational repression of mRNAs 2) mRNA degradation

In regards to leukemia, which class of FISH probe is utilized to assay for: 1) Translocations 2) Deletions 3) Number of Chromosomes

1) Translocation - Dual Fusion probes (DF, F) 2) Deletions - Locus Specific (LSI) 3) Number of ch - Centromeric (Cen)

List the three reactions required to add a 5' 7-MeG cap to pre-mRNA. What enzymes are involved in each step?

1) Triphosphotase (Phosphohydrolase in pic)- Remove primary transcript 5' gamma-phosphate 2) Guanylyltransferase - join incoming Guanine backwards onto 5' end of primary RNA transcript 3) Guanine Methyl-transferase - addition of methyl group onto guanine cap.

At what time range is ultrasound utilized to determine the sex of a fetus?

16-20 weeks of pregnancy. (or 18-20 weeks according to the American Pregnancy Association)

By which two mechanisms is gamma-globin upregulated in HPFH patients?

1) deletion downstream brings enhancer of g-globin gene closer 2) mutation in g-globin promotor region that destroys binding site of repressor. thereby relieving postnatal repression of γ.

What are the four major methods by which genetic mutation leads to disease? Which is the most common?

1) loss of function of the protein (most common) 2) gain of function of the protein 3) acquisition of a novel property by the mutant protein 4) perturbed expression of a gene at the wrong time (heterochronic expression) or in the wrong place (ectopic expression), or both

How many proteins constitute DNA pol III in E.Coli?

17

On which chromosome is the NF1 Gene?

17

How are sequence-specific DNA binding proteins regulated? (5 ways)

1. Conformation altered via ligand binding 2. Entry into the nucleus can be regulated 3. The amount of transcription factor in the cell can be regulated 4. DNA binding can be regulated 5. Phosphorylation of the DNA-binding protein can alter various properties including protein degradation, recruitment of co-activators, and DNA binding

Aside from transcriptional regulation, what are some additional mechanisms to control levels of gene expression?

1. Control of mRNA export from the nucleus 2. Control of mRNA degradation 3. Control of efficiency of translation 4. Control of protein degradation

What are the two classes of chromatin remodeling factors? How do they work?

1. DNA-dependent ATPases (SWI/SNF)- disrupt histone octamers and DNA. 2. Factors that reversibly modify histones through acetylation (HATs and HDACs)

What are the issues with sncRNA Therapy?

1. Distribution and targeting 2. Avoid excretion 3. Avoid degradation 4. Avoid immune rx 5. Extravasation 6. Uptake 7. Endosomal release

What are the primary functions of bone and cartilage?

1. Protection for critical organs (e.g. the ribs for the heart and lungs, the skull for the brain) 2. Mechanical support for locomotion; by supporting and providing attachments for muscles and joints for flexible movement. 3. Calcium and phosphate homeostasis: Bone is a tightly regulated reservoir of calcium for the entire body. 4. To house, protect, and regulate the stem cell precursors of blood cells (the hematopoietic system) (a function of bone).

How do transcriptional activators or repressors, once bound to DNA control elements, stimulate/inhibit transcription?

1. Regulate assembly of initiation complexes and rate of initiation of transcription 2. Regulate changes in chromatin structure influencing the ability of general transcription factors to bind promoters

What are the clinical criteria for diagnosis for someone that has a family history of VHL?

1. Retinal angioma 2. Spinal or cerebellar hemangioblastoma 3. Adrenal or extra-adrenal pheochromocytoma 4. Renal cell carcinoma (Clear cell) 5. Multiple renal and pancreatic cysts

What are alpha-sattelite repeats? How long is the repeated sequence?

171 bp repeat units located near centromeric regions, thought to be important to chromosome segregation in mitosis and meiosis.

What percentage of the human genome codes for proteins?

1.5 - 2 %

What is the incidence of Familial Adenomatous Polyposis; (Familial Polyposis Coli).

1/10000

What is the frequency of NFT1?

1/3000 births.

What are the chances that two individuals affected with achondroplasia will have a child that will die very early in life?

1/4 If they have Achondroplasia and are adults then they must be heterozygotes.

What is the frequency of Marfan syndrome?

1/5000 births.

What percentage of MS patients have a family history?

10%

What percentage of brain lesions in MS cause symptoms in early disease development?

10%

What is the penetrance of Tuberous Sclerosis (TSC)?

100%

What is the penetrance of the Autosomal Dominant disorder Achondroplasia?

100%

What is the odds ratio for getting sickle cell anemia if you have the corresponding mutation?

100% While other diseases rely on a mixture of genetic and environmental factors, sickle cell anemia has no variation from traditional mendelian trait. gene mutation = disease. This is not saying 100% of cells affected. Heterozygotes have portions of cells affected. Either way mutation = phenotypic outcome.

A female with a mitochondrial DNA mutation/disorder: What fraction of her offspring are likely to have the mutation?

100%. All mitochondria in offspring stem from the mother's mitochondria.

On which chromosome are the beta globin and beta-globin like genes located?

11

On which chromosome is the PAH gene?

12

What are the three most gene-poor chromosomes? What deleterious event are these chromosomes viable for?

13, 18, 21. Viable candidates for trisomy

What other trisomies are common? In what clinical presentation do they result?

13, and 18 Can be viable till birth but normally the baby does not survive.

For any given solution what is the sum of pH + pOH?

14

On which chromosome is the SERPINA gene?

14

Relative to their resting volume, to what volume can cells swell before bursting?

140% of resting volume.

On which chromosome is FBN1?

15 Chromosome 15q21.1

On which chromosome is the HEXA gene? HEXB?

15 - HEXA 5 - HEXB

How much total waste (in moles) does our body make in a day? How much waste is excreted via the: 1) GI 2) Kidney 3) Lungs

15 Moles total 1) GI - 300 mMol 2) Kidney - 1200 mMol 3) Lung - 14.5 Moles

What age range is the peak onset for Crohn's and UC?

15-30 yrs old

On which chromosome are the alpha globin and alpha-globin like genes located?

16

At about what distance does a depolarization, generated at a single point across the membrane of neuron, (not a full action potential) reach 1/2 its strength?

1mm. The Neuron is 1 million times less conductive than copper.

When does x-inactivation occur?

1st week of embryogenesis.

How many T-tubules are there per sarcomere?

2

The diameter of an Axon increases by a factor of 4. What does the CV increase by?

2 CV is proportional to the square root of the axon diameter.

Which OH on the branch point A is involved in attack on the 3' end of the preceding exon?

2' OH

How long can a single muscle cell be?

2-3 cm

When do TS babies normally die ?

2-4 years of age

What percentage of sporadic ccRCC are due to VHL loss?

2/3

A patient's parents are both heterozygous for a recessive Disease-Causing mutation. What are the chances that a phenotypically normal progeny of these parents is a carrier of the recessive allele?

2/3 On punnet square, there are 4 possibilities AA, Aa, Aa, and aa. We know she is not aa because she is phenotypically normal. so that leaves AA, Aa, and Aa. So 2 out of 3 of the possibilities. 2/3

A person with unaffected parents has an autosomal recessive disorder. What are the chances their unaffected sibling is a carrier?

2/3 An affected patient with unaffected parents = parents are both heterozygotes. punnet square with omission of the rr (homozygous recessive) leaves two Rr and one RR. so 2/3

What is the increased risk for ATD patients to develop emphysema?

20x increase in risk.

What is the smallest (non-sex) chromosome by size?

21

How long are miRNAs?

21 nt

How long are siRNA?

22nt

What percentage of Marfan's cases are caused by a new mutation?

25%

Where is the TATA box located?

25-35 bp upstream of transcriptional start site (+1)

Aromatic rings in AAs absorb UV at what wavelength? What is an aromatic ring???

280nm Aromatic ring: for our purposes, 6 carbon ring with delocalized electron fields.

In the Hardy Weinberg equation which term represents the frequency of heterozygous carriers?

2pq

If a codon reads 5' - AUG - 3', what does the tRNA anticodon read (assuming no wobble)?

3' - UAC - 5'. Remember tRNA is still RNA, no Thymine (T) present.

Were on the mRNA transcript does the miRNA TYPICALLY recognize and bind?

3' UTR They can also target coding region and 5' UTR

When do the neurological effects of Tay-Sachs begin to affect a TS baby?

3-6 months

At age 30 what is the risk of having a down syndrome baby? at 40?

30 - 1 in 100. 40 - 1 in 10.

How many elastic layers are there in the aorta? How does this contribute to blood flow?

30-40 layers Aorta expands with systole then when the aortic valve closes the elastic recoil of the aorta helps propel blood through the blood stream.

At what age onward do obstetricians normally begin screening pregnant women for trisomy 21?

35

What is the normal age of onset for HD?

35-44

How many genes does mitochondrial DNA encode? What is the primary function of these genes?

37 genes Majority produce components of the respiratory chain .

How many AA are involved in a 180 deg Beta-turn?

4

How many Ca does 1 calmodulin bind? (how many EF hands does it have)

4

How many Ub need to be attached to a protein in order to be signaled for degradation.

4

On which chromosome is the HTT gene?

4

On which chromosome is FGFR3? What is the specific location, the nucleotide?

4 Specifically: Chromosome 4p16.3 nucleotide 1138

What is the pH of a solution bearing an acid with pKa = 4 that is 50% protonated and 50% deprotonated?

4 pH = pKa when acid is 50/50 protonated/deprotonated

How many high energy bonds are required per AA addition to a peptide chain?

4 bonds, 3 molecules. (1 ATP, 2 GTP) To charge tRNA: 2 (ATP->AMP) To deliver aa-tRNA to A site: 1 (GTP->GDP) (EF1a) Translocation: 1 (GTP->GDP) (EF2)

What are the diagnostic criteria for NFT1?

6 or more café-au-lait spots 2 or more neurofibromas 1 plexiform neurofibroma Freckling in the axillary or inguinal area Optic glioma 2 or more Lisch Nodules Distinctive osseous lesions Affected first degree relative

At what age do ccRCC normally manifest in VHL?

60

What percentage of TSC cases are the result of new (de novo) mutations?

66%

What does the ISCN: 69, XXX signify?

69 haploid chromosomes total Triploidy. Female.

What is the basic structure of a g-protein coupled receptor?

7 transmembrane domains that aggregate together.

What percentage of MS patients can be kept from going to secondary progressive if treated early?

8 in 10 will not go to secondary progressive stage if treated early.

What percentage of Achondroplasia patients are results of new mutations?

80%

What is the most common age range in which to develop MS?

80% chance between 16 and 45

How many CGG repeats constitute Full Fragile X syndrome?

>200

What is the plasma glucose level above which is a clear signal for diabetes?

>200mg/dL

How many mutations of p53 have been discovered?

>250

What is p21?

A CDK inhibitor. (part of that whole CDKN thing) Inhibits ALL CDKs.

What is a nucleosome?

A DNA wrapped histone core

What is a quantitative hemoglobinopathy?

A Thalassemia - Disorders of imbalanced globin levels resulted from markedly reduced or no synthesis of one globin type. Can be caused by virtually all types of genetic mutations including deletions, missense and nonsense mutations, and defective transcriptional control.

What is a derivative chromosome?

A chromosome that is the product of a translocation event.

What is satellite DNA? How do they relate to VNTRs?

A class of repetitive DNAs AKA Tandem Repeats: occur in DNA when a pattern of one or more nucleotides is repeated and the repetitions are directly adjacent to each other. VNTRs are just tandem repeats that vary in length in the population. "fingerprints" in that they are rarely the same between any two individuals.

What are Dispersed repetitive elements? What normal DNA restructuring occurs within these?

A class of repetitive DNAs Transposition of genetic material (DNA)

What affects solubility of nucleosides/tides?

Affects: Level of phosphorylation: more phosphorylation = more soluble. More rings (in bases, which are hydro phobic): less soluble. More rings is more hydrophobic. Solubility: Pyrimidine > Purine Nucleotide > nucleoside > bases Some diseases block the phosphorylation of nucleosides, cause less solubility, aggregation.

What is Ritonavir?

A competitive inhibitor of HIV protease.

What is a CNV?

A copy number variation (CNV) is when the number of copies of a particular gene varies from one individual to the next.

What is a multiplex family?

A family with multiple members having same disease

What is Tay-Sachs?

A fatal genetic disorder in children that causes progressive destruction of the CNS

What specifically is DNA ligase binding?

A free 3' OH to a free 5' phosphate.

What is a holocrine gland? What is an example of this?

A gland functioning via whole-cell-disintegration. Secretion of oil onto hair and skin.

What is a motor unit?

A group of muscle fibers innervated by a single neuron.

What are the diagnostic criteria for LFS?

A proband with a sarcoma diagnosed before 45 years of age AND A first-degree relative with any cancer under 45 years of age AND A first- or second-degree relative with any cancer under 45 years of age or a sarcoma at any age

What is the kinetochore?

A protein structure on chromatids where the spindle fibers attach during cell division to pull sister chromatids apart.

What occurred in a patient who is Trisomy for 8q22.1 and Monosomy for 8p23.1?

A recombination event in meiosis between a normal ch8 and a pericentrically inverted ch8. (Loss of p material and gain of q material)

What is a reflection coefficient? What do reflection coefficients of 0, .5 and 1 signify?

A relative measure of the osmotic pressure exerted by a fluid in relation to water across a semi-permeable membrane. 0 = same as water .5 = half as easy to cross membrane as water 1 = can not cross membrane Think of it as how much something is reflected. If 0, not reflected at all. If 1 is fully reflected. Consider this example: Suppose we bathe a cell (internal osmolarity= 300 mosM; nonpermeating internal solute) in a 600 mosM solution of solute that can cross the membrane half as easily as water (σ = 0.5). When first exposed to the solution, water will not move across the membrane, because there is no osmotic force (1x300= 0.5x600). Then, as solute enters the cell, water will follow, and eventually the cell will lyse.

What is a transcription factor?

A separate protein that binds DNA at DNA transcription control elements and regulates transcription of genes.

Does one miRNA regulate one mRNA? What is its degree of specificity?

A single miRNA may target many different mRNAs It has been estimated that ~1,000 miRNAs are thought to regulate over 50% of all genes in mammalian cells

What is the basal lamina? What is it made of?

A thin sheet of extracellular material that underlies the basal surface of each epithelial tissue. Composed mainly of Type IV collagen along with lamins and enactins (glycoproteins) Composition can change between different epithelium of the body.

What is a transcriptional enhancer?

A transcription regulator working from a long distance. Can be upstream or downstream from start site. Work to loop the DNA from a great distance.

What is the L1 family of Repetitive DNA sequences? How long are they and how numerous?

A type of LINE (LINE 1 = L1). ~6 kb related members ~100,000 copies in genome

What is the Alu family of Repetitive DNA sequences? How long are they and how numerous?

A type of SINE characterized by the action of the Alu (Arthrobacter luteus) restriction endonuclease. Alu elements are the most abundant transposable elements in the human genome ~300 bp long ~500,000 copies in the human genome.

What is Li-Fraumeni Syndrome?

A very rare inherited cancer susceptibility syndrome that has a huge range of presentation: Elevated risk for a wide range of cancers, Childhood cancer, early onset breast cancer, present later (after age 50). but commonly sarcomas, pre-menopausal breast cancers, adrenocortical tumors, leukemias and lymphomas.

What is genetic mosaicism? (think of mosaic presentation of trisomy 21) How is this possible?

A zygote containing two cell lines which differ in chromosome number Mechanism: Gametes are normal. Fertilization and fusion normal. The abnormal event occurs in an early MITOTIC division of somatic cells in embryonic development. This event can be: non-disjunction Anaphase lag - a homologue fails to attach to the spindle in anaphase (most common) Endoreplication - replication of the nuclear genome in the absence of cell division

You have sampled a population in which you know that the percentage of the homozygous recessive genotype (aa) is 36%. Using that 36%, calculate the following: A) The frequency of the "aa" genotype. B) The frequency of the "a" allele. C) The frequency of the "A" allele. D) The frequencies of the genotypes "AA" and "Aa." E) The frequencies of the two possible phenotypes if "A" is completely dominant over "a."

A) 36% B) .6, or 60% C) .4 or 40% D) AA = .16 (16%), Aa = 48% E) aa pheno = 36%, AA+Aa pheno = 64%

What is Keq?

A+B <-> C+D Keq = [C][D]/[A][B]

What does AP-site mean?

A-Basic site in a DNA chain. Has backbone, but no associated base AP = A purinic/pyrimidic

What are alpha and beta thalassemia?

A-thalassemia - low or zero a-globin, b-globin in excess & precipitates. B-thalassemia - low or zero b-globin, a-globin in excess & precipitates.

What is Osteogenesis Imperfecta?

AD Disease. Genetic bone condition 'imperfect bone formation'. Feeble bones break and fracture easily.

What is Tuberous Sclerosis?

AD Disease. TSC - A rare multi-system genetic disease that causes benign tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin.

What is Marfan Syndrome?

AD disease systemically affecting connective tissues. Most commonly skeletal, cardiac, and ocular.

What is Neurofibromatosis?

AD disease. Tumor disorder caused by genetic mutation

What is Androgen Insensitivity Syndrome? What causes it and what are its clinical presentations?

AIS - 46, XY. X-linked gene - Androgen receptor. Mutation causes abnormalities in the Androgen Receptor. Even though the body makes androgens (testosterone), it doesn't necessarily recognize or respond to it Phenotypes range from mild under-virilization (Partial AIS) to full sex reversal (Complete AIS) Previously called "Testicular feminization"

What are antagonists of the b-adrenergic g-protein coupled receptor? Which two did we discuss?

AKA Beta Blockers, meds used to lower BP. Propanolol, Carvedilol and Metaprolol

What is a karyopherin?

AKA importins and exportins. Transport molecules that facilitate movement of other molecules through the NPC.

Which endonuclease cuts second in BER repair, thereby removing the backbone of the damaged site?

AP Lyase

What endonuclease cuts first in BER repair? Where does it cut?

APEI endonuclease 5' to the a-basic site.

Which leukemia can be treated with retinoic acid? What is RA action?

APML. RA - binds to the novel (translocation product) protein. alters its conformation, allows cellular differentiation.

Why are autosomal dominant diseases less likely to be passed on where autosomal recessive are more likely?

AR disease harder to identify. If an AD disease causes shortened or loss of life, then can not pass on (low fitness). AR carriers can be clinically normal. Hard to detect phenotypically.

Describe the structure and function of the androgen receptor in prostate cancer.

AR free in cytoplasm -> Binds ligand (androgen) -> inhibitory chaperones leave AR, AR homodimerizes -> Entry into nucleus -> Binding to DNA -> recruiting of coactivators -> up regulation of transcription of genes.

What mutated gene and protein are associated with each of the following diseases ATD Tay-Sachs Sandhoff Sickle Cell

ATD - Gene: SERPINA, Protein: Alpha 1 Antitrypsin (AKA SERPINA1) Tay-Sachs - Gene: HEXA, Protein: HexA (-> Hexasaminosidase A) Sandhoff - Gene: HEXB, Protein: HexB (-> Hexasaminosidase A) Sickle Cell - Gene/Protein: B-globin Remember Hexasaminosidase A is a heterodimer of HexA and HexB.

What are the two member of the PIKK family of proteins that are involved in transaction of signal to the cell that DNA damage has occurred?

ATM and ATR. They are kinases that signal the cell about DNA damage (not just double stranded)

What does DNA ligase use to seal the nick in DNA backbone? How much of this substance per nick-seal?

ATP 1 per nick, so 2 per complete joining of both sides of DNA backbone.

Actin monomers bind which energetic molecule? And tubulin monomers?

ATP - actin GTP - Tubulin

Where does the phosphate, added to proteins by kinases, come from?

ATP - the gamma phosphate.

What signaling molecule can ATP be converted to?

ATP -> AMP which can become cyclic AMP (cAMP)

Does ATP or ADP bound actin like to polymerize?

ATP bound.

What are the general differences between African and Asian alpha-thalassemias?

African - Haplotype always has one one functioning allele Asian - Haplotype has either both active or both inactive, results in more Hydrops Fetalis

Which gene is mutated in Cystic Fibrosis?

ATP-binding cassette transporter gene on chromosome 7. (Encodes CFTR protein)

Which kinases are crucial in recognition and down stream activation in DNA lesions, breaks, or stalled replication forks?

ATR and ATM which signal CHK1 and CHK2. These kinases act to signal production of DNA repair enzymes and apoptosis if needed. These kinases are commonly mutated in cancer cells. (p53/apoptosis pathway shown)

Name the start codon and what amino acid it encodes.

AUG - Methionine

What is the difference between Abiraterone and Enzalutamide and how do they work to circumnavigate PCA cancer cell resistance to hormone therapies?

Abiraterone - shuts down androgen production Enzalutamide - shuts down AR All hormone resistance therapies (castration) can be circumnavigated by cancer cells either making their own androgens, making more AR, or mutating AR to be always on. While Abiraterone stops androgen production, cancer cells can still mutate AR to always be on. Enzalutamide directly inhibits AR in many ways, so no amount of androgen will activate AR, nor will mutant AR be functional. (In some cases. Mutant AR may bypass Enzalutamide action)

What is bradycardia?

Abnormally slow heart rate.

What is the basic mechanism of CF?

Affects many organ systems in body, most notably lungs. Mutations in CFTR cause lack of Cl release from cell and thereby lack of H2O diffusion into lumens areas. Causes thick secretions in many areas (lungs, pancreas, sinus)

Describe how neuronal action potential results in contraction of the sarcomeres in a muscle. List all steps

Action potential from CNS -> Vesicle fusion at synapse -> release of Acetylcholine -> Binding of acetylcholine receptors on muscle cell plasma membrane -> The AChR is an ion channel that opens and causes depolarization -> The depolarization of muscle cell in turn will open Na channels and an action potential is initiated -> Action potential travels via t-tubule system affecting whole cell -> Via EC coupling t-tubule AP affects SR Ryanodine receptor -> Ca release from SR via Ryr -> Calcium binds troponin -> Moves tropomyosin -> Myosin binds actin -> Repetitive ATP/Ca dependent power strokes.

What are some examples of how proteolytic cleavage contributes to proper protein function?

Activation of digestive enzymes such as trypsin, chymotrypsin. Activation of insulin. Activation of complement enzymes. Activation of blood clotting. (cascade involves many steps of specific protease activity, cleaving) Activation of some transcription factors eg Notch. Activation of enzymes involved in programmed cell death.

In regards to HATS and HDACs. Which does a transcriptional activator recruit? A transcriptional repressor?

Activator - HAT, loosen DNA Repressor - HDAC, tighten DNA Sooo, HATs are co activators and HDACs are co-repressors.

What binds transcriptional enhancers?

Activators

In reference to 'High' and 'Low' CDK, what is actually meant by that? Amount? Activity?

Activity. CDK is constituently expressed. Its everywhere all the time. Cyclin is the molecule that varies in concentration (thats why its called cyclin, varies in cycles) and thereby regulates the CDK activity. (cos CDK is dependent on cyclin to operate remember?)

Ketoconazole is an anti fungal medication. Why is it used in the treatment of prostate cancer?

Acts to inhibit adrenal gland enzymes necessary for the conversion of cholesterol to steroid hormones such as testosterone and cortisol. Blocking testosterone limits ligand availability for the AR receptor and will therefore downregualte AR-transcribed genes.

More acute Psi angles lead to what secondary structure? and More obtuse?

Acute - Right handed Alpha-helices Obtuse - Beta Sheets.

What type of leukemia is associated with the translocation t(15;17)?

Acute Pro-Myeloid leukemia (APML)?

What are the characteristics and clinical presentations of Cholera?

Acute, MASSIVE watery diarrhea - can lose whole body fluid and die in a day. - Cholera stool = looks like rice water Dehydration - decreased pulse volume - low BP - sunken eyes Vomiting Abd pain renal failure low K+, Ca++ Low HCO3- Only infects humans Explosive epidemics. Pandemic - worldwide effects.

What is the method in which the genetic disorder, Down Syndrome, can be treated without directly addressing the underlying genetic defect?

Addressing: - cardiac - improvements in surgical techniques - hyper/hypo thryoidism - Depression Etc The take-away: Genetic disorders can be treated to increase longevity drastically (47, +21 used to have life expectancy ~1yr old) by treating the disease without directly addressing the underlying genetic abnormality.

What does glycosylation add to an AA in post translational AA modification? What does this do? Which type of proteins is this typically added to?

Adds a sugar. Increases solubility, among other things. Typically added to proteins that are either to be secreted or that are bound for the cell surface.

What is the name for cancers derived from glandular epithelium?

Adenocarcinoma

What two types of cell junctions use cadherins?

Adherence junctions and Desmosomes

In regards to segregation of chromosomes that have undergone translocations, what are the two types?

Adjacent and Alternative

What are the clinical Manifestations of MD?

Adult onset muscular dystrophy Progressive muscle wasting and weakness Myotonia Cataracts Cardiac conduction defects

What population has the highest carrier rate for HbS? What percentage of the population?

Africans 15%

In which phase of mitosis are the sister chromatids pulled to opposite sides of the cell via the spindle system?

Anaphase.

Identify the sources of androgen in the body relevant to prostate cancer.

Androgens are produced primarily in the testes (Leydig cells) and then to a lesser degree in the adrenal glands. ALSO, the prostate cancer cells produce their own testosterone.....recent discovery

What disorder results when there is a deletion or an imprinting of the maternal allele of chromosome 15 in the PWS loci?

Angleman syndrome (AS)

A cell has a Vm of -40 mV. It is permeable to Cl . [Cl ]o= 130 mM and [Cl-]i= 13 mM. Must there be a pump for Cl-, and if so, in which direction is Cl- pumped?

Answer: From the Nernst equation, ECl= -60 mV, which is different than Vm. Because the membrane is permeable to Cl-, there must be a Cl- pump, because Cl- is not at equilibrium. Now the hard part: in which direction does it pump the Cl-? There are different ways to think about it. Here's one way: the Nernst equation says that to balance a ten fold concentration gradient (130 mM outside, 13 mM inside) we need a 60 mV membrane potential (inside negative, because it's an anion). The electrical arrow says, "I need -60 mV to counter exactly the concentration force". Ah, but the real membrane potential, Vm, is only -40 mV; the real arrow is shorter by one-third than the one drawn. Thus, the net force on the ion is-into the cell (the net force is obtained by adding the two arrows). So the pump must pump Cl out of the cell.

A cell is permeable to H+ ions. [H+]o= 50 nM, [H+]i= 100 nM, and Vm= -80. In which direction is H+ pumped?

Answer: H+ is pumped out. E = 60*Log(50/100) = -20mV and Vm = -80mV H+ will ENTER the cell (again, it is permeable, it leaks in) to make the inside of the cell more positive (make Vm more like E), so to maintain this E this Vm, H+ must be pumped OUT.

What is the mechanism and effect of the drug Puromycin?

Antibiotic. Mimics the 3' end (acceptor, amino acid charged) of tRNA. Enter ribosome and are incorporated into growing polypeptide chain. Terminates Translation.

Name four components of the RNA polymerase II pre-initiation complex.

Any 4 of the following: TFIIA, TFIIB, TFIID, TFIIF. TFIIE, TFIIH, activators or mediator.

Describe the process at the mitochondrion in apoptosis (intrinsic pathway)

Apoptotic signals upregulate pro-apoptotic elements (Bim, PUMA) to go to mitochondrial surface and inactivates Bcl2 (anti-apoptotic resident factor) which allows Bax to permit cytochrome C oxidase to leave the mitochondrial interior. Cytochrome C oxidase -> Caspase 9 -> Caspase 3 (executioner)

What protein is involved in actin branching?

Arp2/3

Which protein processes the ends of dsDNA for proper NHEJ to occur?

Artemis

What population is at a higher risk for TS? What is the increased risk? Same for Sandhoff?

Ashkenazi Jews 100 fold increased risk. No increased risk in Ashkenazi Jews for Sandhoff

What population group is more at risk for contracting Gaucher's Disease? Which type of Gaucher's primarily affects them?

Ashkenazi Jews. Type 1

To what AA is the lipid-linked oligosaccharide transferred in N-Linked glycosylation?

Asp (N) ..so N linked.

Where do noncompetitive inhibitors bind?

At a site other than the active site (where the substrate binds)

At what pH is a buffer most effective?

At the buffer's pKa. Buffer works best in the range of its own pKa.

What specific cardiac anomaly is most common in patients with down syndrome?

Atrioventricular Canal

What are the important functions of the basal lamina?

Attachment, filtration, polarity, transport, barrier, gene expression, scaffolding 1. Attachment - Mediate attachment of epithelia to the underlying connective tissue. 2. Filtration - Filtration of substances diffusing to or from the epithelia. 3. Polarity - Establishment and maintenance of epithelial cell polarity. 4. Transport - Serve as specific "highways" for the migration of cells through connective tissue. 5. Barrier - Barrier to movement of invading microbes or cancerous cell into other tissues. 6. Gene Expression - They control the gene expression of cells to affect their proliferation or development. 7. Scaffolding - They control the development, morphogenesis, and organization of epithelial cells, providing a sort of "tissue scaffolding" function. Thus, they are critical to the repair of epithelial tissue following damage by injury or disease.

What two genes are fused in t(9;22)?

BCR, ABL. Fusion between the Abelson (ABL) tyrosine kinase gene at chromosome 9 and the break point cluster (BCR) gene at chromosome 22, resulting in a chimeric oncogene (Bcr-Abl) and a constitutively active Bcr-Abl tyrosine kinase that has been implicated in the pathogenesis of CML

Describe basic clinical features of Multiple Sclerosis (MS).

Auto-immune disorder. Clinical features: Inflammatory attack on myelin in CNS causes Fatigue Walking impairment Spasticity Cognitive impairment Bladder dysfunction Pain Mood instability Sexual dysfunction Paresthesia, numbness, tingling.

What system regulates both endocrine and exocrine secretions?

Autonomic nervous system. (sympathetic and parasympathetic)

How can autophagy inhibit neurodegeneration?

Autophagy also engulfs and degrades aggregated proteins. Misfolded protein aggregation is a cause for many neuronal diseases.

What is the inheritance pattern of NFT1?

Autosomal Dominant

What is the inheritance pattern of Von-Hippel Lindau disease?

Autosomal Dominant

What inheritance pattern is shown by LFS?

Autosomal Dominant.

What is the inheritance pattern for ATD?

Autosomal Recessive

Describe 5α reductase deficiency And its Mechanism.

Autosomal Recessive. Sexual ambiguity in males. Ambiguous external genitalia in 46 XY males, Failure of end organs to activate testosterone to dihydrotestosterone (DHT) in 46, XY individuals; 5- alpha reductase needed to covert tetosterone to active DHT

What inheritance pattern is followed by achrondroplasia?

Autosomal dominant.

What is cystic fibrosis (CF)? What gene is mutated?

Autosomal recessive genetic disorder mostly affecting the lungs. Frequent lung infections. CFTR Gene

Describe Pompe Disease. And its Mechanism.

Autosomal recessive lysosomal storage disorder Progressive muscle failure, cardiomegaly, hypotonia, cardiomyopathy, respiratory distress, muscle weakness, feeding difficulties, and failure to thrive (used to die by 1 yr) Accumulation of glycogen in the lysosome due to deficiency of the lysosomal acid alpha-glucosidase enzyme

What type of DNA repair is used for fixing oxidative damage to DNA?

BER - cos it does not distort DNA

Two acrocentric chromosome's q-arms join at a single centromere. Is this balanced or unbalanced?

Balanced.

What are the two major classes of structural aberrations in chromosomes? What genomic modifications cause each?

Balanced: Normal compliments of gnomic material, but bearing translocations and inversions. Unbalanced: Abnormal chromosomal compliments owing to deletions, duplications, Isochrosomes, Marker Chromosomes, Recombinant chromosomes.

Explain the primary features Waddingtons epigenetic landscape

Ball at top = stem cell. High energy state. Undifferentiated Ball at bottom - cell has differentiated, is now in lower energy state. Cell fate acquired.

What are two examples of ciliopathies?

Bardet-Biedl Syndome (BBS) and Polycystic Kidney Disease (PKD) BBS - shuts down vesicle transport within the cilium. Symptoms: • Photoreceptor degeneration • Anosmia • Mental retardation / Developmental delay • Neural tube defects • Obesity • Hypogonadism • Kidney defects • Polydactyly • Diabetes PKD - affects channels that sense mechanical flow via cilium. Symptoms: • Renal cysts • Liver and pancreas cysts • Intracranial aneurysms

What is the structural difference between a basal body and an axoneme?

Basal body - nine triplet MTs in a ring. Axoneme - Nine doublet MTs in a ring with two central MTs. They are considered A, B, and C MTs with axonemes having AB and Basal bodies having all three

If centrioles only duplicate at the G1 to S phase transition, how can a cell with a high need for cilia generate enough basal bodies?

Basal body assembly is uncoupled from the cell cycle and replication is amplified to facilitate the multiple basal bodies required for ciliogenesis in multi-ciliated epithelial cells.

How does Cisplatin work to affect DNA replication?

Base Alkylating agent .Covalently attached large adducts to bases in DNA chain, halts replication machinery.

What type of DNA damage does Base Excision Repair fix?

Base damage that does NOT distort DNA.

How are kinases classified?

Based on the AA they phosphorylate (Ser, Thr, Tyr), their substrate, their activation, or their phylogenetic relationship

Are the polar positive amino acids basic or acidic?

Basic. While this may seem counter intuitive as these have gained an H+, think of it as though the basic group of the AA (-NH3+) is now charged.

What are the benign and metastatic treatments for VHL disease-related RCC?

Benign - surgical resection and monitoring Metastatic - systemic therapy including vascular endothelial growth factor receptor (VEGF-R) tyrosine kinase inhibitors, MTOR inhibitors, and immunotherapies.

SCD mutation are in the alpha or beta globin chain?

Beta

Which protein helps DNA pol III in prokaryotes hold on to DNA in replication? What factor of DNA polymerase is this protein increasing?

Beta Clamp. Increases processivity

Give an example of how the amount of an activator/repressor can be regulated within the cell.

Beta catenin- In the absence of Wnt signaling, the cytoplasmic pool of β-catenin is targeted for degradation through the ubiquitin-proteasome pathway. In the presence of Wnt signaling, phosphorylation of β-catenin is prevented, leading to an increase in the cytoplasmic pool of the protein. This increase allows some of the β- catenin to move to the nucleus, where it promotes the expression of Wnt responsive genes. p53- is downregulated by binding to the MDM2 protein which not only masks its activation domain, but also targets it for destruction by the ubiquitin-proteasome pathway. MDM2 can also bind to activation domain of p53 and block transcription.

What is albuterol? What does albuterol do in lungs?

Beta-Adrenergic agonist Bronchodilation

Where is the restriction point in the cell cycle? Why is it significant?

Between G1 and S phase. Once you pass this point the cycle continues completely around. This is also the point at which a cell will not enter s-phase but will divert and choose to differentiate

What are three abnormalities of the Cardio Vascular System (CVS) in Turner syndrome patients?

Bicuspid Aortic Valve - only two leaflets on valve, supposed to be three. Coarctation of the Aorta - Narrowing of the aorta Systemic Hypertension - High BP.

What does Ca binding do to C2 domains? How many Ca can a C2 domain bind?

Binding of Ca to a C2 domain causes it to associate with the plasma membrane. C2 domain binds 3 Ca

What are the two major functions of the 3' poly AAA tail?

Binding of the Poly A Binding Protein (PABP) to Poly A site: 1) greatly stabilizes mRNA 2) Enhances translation at the ribosome.

What is the function of Insig?

Binds SCAP which causes SCAP to not bind SREBP and therefore not have the SREBP/SCAP complex migrate to golgi (no bHLH cleavage)

In which process is COP 2 involved?

Budding vesicles from ER -> Golgi

In which process is Clathrin involved?

Budding vesicles from the trans golgi network towards the plasma membrane.

In which process is COP 1 involved?

Budding vesicles going back to ER from Golgi

How can nuclear import/export be regulated?

By affecting the cargo, the transport receptor protein or the NPC itself. See slide for details. Bottom is most common.

How do pericentrically inverted chromosomes achieve proper pairing in Meiosis?

By forming a loop structure that allows as much contact between homologous areas of the chromosome as possible

In regards to free energy, how does an enzyme affect the rate of a reaction?

By lowering the activation energy. Remember that only activation energy affects reaction rate. (

How does a hydrophilic molecule pass through the NPC and its associated barrier nucleoporins?

By recruiting an amphiphilic carrier molecule that can escort it through the NPC. Amphiphilic molecules are molecules that can associate with hydrophilic and hydrophobic regions alike.

Hormone testing for a newborn with ambiguous sexual characteristics must be performed by when? Why?

By the end of the first day of life. Because these hormonal levels are present during the first day of life, and can denote what the body is internally signaling. Normally by the second day many of these hormones have gone dormant.

What disease is associated with Der(9;22)? What two genes are fused in this? What are the resulting gene expression patterns?

CML - Chronic Myelogenous Lukemia BCR and ABL fused. ABL, not normally expressed in many cells, now, due to fusion with BCR promoter, is expressed. Now is constitutively active tyrosine kinase -> unregulated cell proliferation.

What are two Ca binding motifs and in which proteins are they located (examples)?

C2 - in PKC and synaptotagmin EF hand - Calmodulin.

What is the nucleotide repeat in Huntington's disease?

CAG

What is the mechanisms and result of HD?

CAG repeats in the HTT gene -> Mutated Huntingtin -> Causes neuronal atrophy in the caudate nucleus of the basal ganglia (resulting in involuntary muscle twitching and jerking), slowly progressing to death in 5-15 years.

What two proteins bind to the 5' cap? Where in the cell do they bind? What to they assist in?

CBC - Cap Binding Protein - in the nucleus Function 1) Nuclear export 2) Splicing 3) 3' Processing ELF4E - in the cytoplasm Function 1) Translation.

Which protein that binds the 5' cap is essential for splicing and maturation of the mRNA message?

CBC - Cap Binding Protein.

HIV only fuses with (Affects) which cells?

CD4. (AKA T-Cells, T-Helper cells). Regulated by binding directly to CD4 membrane proteins.

What disease is associated with a deficiency in glycosylation?

CDG - Congenital Disorder of Glycosylation.

Which CDKs inhibit Rb?

CDK 2, 4, and 6.

What are CDKNs? Are they inhibitors or activators of the cell cycle?

CDK inhibitors. So thy are inhibitors of the cell cycle.

If CDK 2 and CDK 4,6 are constitutively produced how is their activity regulated?

CDK stands for cyclin-dependent kinase. Its not active without cyclin. The cyclins needed for CDK2 / 4,6 activity (CycD 1-3 and CycE) are what is regulated.

How are CDKs and Helicases related in cell cycle regulation?

CDKs activate LOADED helicases to trigger S phase but also block NEW loading of helicases.

What is the trinucleotide repeat in Fragile X?

CGG

What trinucleotide repeat is associated with Fragile X syndrome?

CGG

What are the CGG repeat numbers for each of the classifications: Normal range Grey Zone Premutation Full Mutation

CGG Repeats 6-45 Normal range 46-55 Grey Zone 56-200 Premutation >200 Full Mutation

What is the complete molecular mechanism of Fragile X?

CGG repeats present in FMR1 gene in excess of 200 repeats -> Increased C residues = increased methylation sites -> Silencing of FMR1 -> Lowered FMRP levels -> Impaired cognitive development.

What is another name for the first relapse in MS?

CIS - Clinically isolated syndrome.

What is the most common clinical presentation in VHL? Around what age does it present?

CNS hemangioblastomas. 80% of all patients. ~30 years old.

What is the trinucleotide repeat in Myotonic Dystrophy?

CTG

What is CYP 17?

CYP 17 is an essential enzyme in testosterone/estrogen production.

What is synaptotagmin and how does it function in response to Ca?

Ca binding to Synaptotagmin is involved in vesicle docking and vesicle fusion.

Describe smooth muscle contraction.

Ca influx -> Binds calmodulin -> Ca-Calmodulin activate CaM Kinase -> Phosphorylation of Myosin light Chain head -> power stroke by myosin on actin. This process is much slower than skeletal/cardiac contraction, but still uses ATP for myosin release and reset in power stroke sequence.

What are the primary minerals/ions utilized in ossification of the bone matrix?

Ca++ - Calcium PO4 - Phosphate

What is the mechanism of Ca in muscle contraction?

Ca++ influxes into myofibril, binds

Describe cadherins. Function, production...

Cadherins bind cells to one another via homodimerization in a zipper like fashion. Cadherins are transmembrane proteins that are constantly produced and recycled by the cell. If not bound to other cell's cadherins, they are recycled.

What is a common PDE blocker?

Caffeine.

Recombination between two acrocentric homologues (one normal one with a paracentric inversion) can produce what products? Are they all balanced/viable?

Can form balanced, normal products or can form products with two centromeres (one at either end) or an acentromeric chromosome. Both centromeric malformations result in inviable chromosomes.

How can siRNA and miRNA be used for therapy?

Can tailor siRNA or miRNA sequence to target a certain mRNA in the cell for cleavage and degradation.

What are the two genetic association studies? What are their traits and differences?

Candidate Gene study - Focuses on associations between genetic variation within pre-specified genes of interest and phenotypes or disease states. (uses hypothesis) Genome Wide Study (GWAS) - looks as whole genome for associations with traits. (Hypothesis-free) Candidate gene presupposes that the single gene, chosen in advance of study, is the cause of the trait (normally wrong) where GWAS is looking for whole genome differences that can lead to the trait (correct)

Which vessels contain no smooth muscle?

Capillaries and some post-capillary venules.

Where does the capping protein in actin filaments bind? What happens if Arp2/3 becomes unbound?

Capping binds ATP bound (Aka 'plus', or 'polymerizing') end. if Arp2/3 unbinds actin de-polymerizes from ADP end.

What is the name for a cancer of epithelial origin?

Carcinoma

How are carcinomas believed to arise?

Carcinomas result from defects in regulatory pathways that control epithelial stem cells or their progeny during tissue development and maintenance

List the medical problems with which a DS patient may present.

Cardiac Gastrointestinal Ophthlamologic ENT Endocrine Orthopedic Hemotologic Developmental

In each muscle cell type (Skeletal, cardiac, smooth) where is the nucleus located?

Cardiac and Skeletal - periphery Smooth - central.

What types of tissues can mesenchymal stem cells (MSC) generate?

Cartilage and bone.

What is the main initiator caspase (signaling) for the extrinsic pathway in apoptosis? What does it do?

Caspase 8 Activates the effector (executioner) caspase, Caspase 3. BOTH the intrinsic and extrinsic pathways result in activation of caspase 3

What is the main initiator (signaling) caspase for the intrinsic pathway in apoptosis? What does it do?

Caspase 9 Activates the effector (executioner) caspase, Caspase 3.

What are the structure and function/purpose of microvilli?

Cell surface extensions (protrusions) that contain actin bundles connected to cytoskeletal elements in the cell interior. The primary function of microvilli is to increase surface area, which greatly increases the rate/efficiency of membrane transport and secretion

Describe an adherence junction.

Cell to Cell attachment junctions that utilize caherins and can be regulated by regulating cadherin.

Describe the interferon pathway in viral defense

Cells infected with virus produce and secrete interferon protein to surrounding cells. Neighboring cells, in advance of viral infection, gain interferon which phosphorylates eIF2 -> Stops translational initiation. Stoppage of translation means that the virus-mRNA can not be translated into proteins that seek to alter the cell on a genomic level.

What types of cels give action potentials?

Cells with very negative E (except for glia) - Muscle ~ -80 - Neurons... ~ -70

What is the role of microtubules in mitosis.

Centrioles replicate in S phase just like the DNA. Centrioles/Centrosomes travel to opposite ends of mitotic cell along with their associated MTs. MTs attach centrioles to cell membranes, to kinetochores of mitotic chromosome pairs, and to other MTs. MTs pull sister chromatids apart in mitotic division.

What is the leading cause of death and disability in pediatric DKA?

Cerebral Edema 1/4 die, the rest are likely to have brain damage.

What is stronger, charge forces or osmotic forces?

Charge, by a loooooooooot. It is the strongest force in biology. (nuclear reactions do not occur in biology)

Describe the chemical reaction catalyzed by RNA polymerase and why it is unidirectional.

Chemical reaction - formation of the phosphodiester bond Unidirectional - because RNA is single stranded. The gene only reads one way, not both. DNA bidirectional replication because is double stranded.

What is CFTR?

Chloride channel on apical side of epithelial cells.

What type of ion channel is mutated in Cystic Fibrosis? What does that cause?

Chloride channel. Blockage of Cl- channel blocks passage of Cl- from blood to mucous/endothelial lining of airways. No Cl- movement means no H2O or Na+ movement. Leads to dry mucous, sticky, no moisture of airways.

What type of cells make cartilage matrix and tissues?

Chondrocytes

Prenatal Diagnosis: what are the two methods by which fetal genomic samples are acquired?

Chorionic Villi - Direct sample from placenta. Trans vaginal Amniocentesis - Sample from fluid surrounding fetus. Abdominal puncture

On which chromosome is TSC2? What protein does it encode? What does that protein do?

Chr 16 Protein - Tuberin Funciton: Regulates cell growth and proliferation. (tumor suppressor)

On which chromosome is TSC1? What protein does it encode? What does that protein do?

Chr 9 Protein - Hamartin Funciton: Regulates cell growth and proliferation. (tumor suppressor)

What is a chromosomal micro array CMA? Mechanism? What does it detect? What does it not detect?

Chromosomal Microarray. Bunch of oligonucleotides of known sequence adhered to a grid. Sample exposed to this grid, sample binds in certain grid coordinates, which light up. Detects relative expression patterns (amounts) only. Can NOT detect balanced translocations (no gain or loss of genetic material)

What chromosome is abnormal in Prader-Willi Syndrome (PWS)? In what ways can it be different?

Chromosome 15 - multiple genes (PWS loci) The paternal contribution to Ch 15 may be lacking OR the maternal contribution to Ch 15 is in disomy (doubled). Prader-Willi Syndrome results when genetic information is missing from the paternal allele of the PWS Loci of Chr 15. This region of chromosome 15 is imprinted differently for maternal and paternal contributions, so it is critical that information from both the maternal and paternal alleles are present for a person to be normal. PWS may result because of a deletion of the paternal allele, or because of uniparental disomy ( UPD - 2 copies present from one parent) of the maternal allele, or because of an imprinting error in how the alleles are marked, causing "virtual" maternal UPD.

List of the chromosomal locations of genes (mutations related to disease) discussed in Unit 2

Chromosome: 1 - Glucocerebrosidase 4 - HTT, FGFR3 5 - HEXB 9 - TSC1 11 - B-globin 12 - PAH 13 - GJB2, RB1 14 - SERPINA 15 - HEXA, FBN1 16 - A-globin, TSC2 17 - NF1 19 - DMPK 21 - Down syndrome, Alzheimers X - GLA, FMR1, DMD Y - SRY

What type of leukemia is associated with t(9;22)?

Chronic Myelogenous Leukemia (CML)?

In what stage of the cell cycle do cilium form? and when do Centrioles form?

Cilia - G1 Centrioles - Transition into S phase

What is Motile cilia and what is its function?

Cilia that wave back and forth (beat) to move apical factors (mucous, ovum...) along the surface of epithelium along passageways.

Which side of the golgi receives the buds from the ER?

Cis

Why does the refractory period exist?

Some inactivation gates on the Na+ channels are still closed unable to respond well to depolarization AND Some K+ activation gates are still open, thereby continuing to make the MP more negative.

What is dicer? What does it do?

Cleaves double-stranded RNA molecules into 21-25-nucleotide- long double-stranded RNA with a two-base overhang on the 3'-ends.

Activation domains of transcription factors can draw in what other factor that assists in transcription?

Co-factors.

What codon in both Sickle cell and Hemoglobin C disease is mutated in certain beta-globins?

Codon 6.

How can Sickle cell be diagnosed using RFLP?

Codons 5,6 and 7 of the NORMAL beta-globin gene contain a palindromic sequence (CCTNAGG) (N can be anything, still palindromic) that is recognized by the R.E. MstII. Mutation at the 6th codon (SCD) disrupts palindrome, alters cut sites. No cut = longer product at that loci. Can assay and southern blot DNA to look for either longer strand or MstII cut shorter strand.

How does dystrophin contribute to muscle structural integrity?

Cohesive protein. Attaches actin filaments to the cell membrane of a muscle cell.

What is the protein product of COL1A1? What does it do?

Collagen type 1 Alpha 1 COL1A1 protein is the major component of type 1 collagen which is the most abundant collagen in the body (connective tissue, bones...)

What is the most abundant connective tissue in the ECM?

Collagen. Specifically Type 1

Mutations in APC are associate with which human cancer?

Colon cancer

What is combinatorial control?

Combining transcription factors in different homo- or hetero-dimerizations that alter their ability to bind a wide array of DNA control elements for differing genes.

What is achrondroplasia?

Common cause of dwarfism. GOF disease. Caused by a GOF mutation in fibroblast growth factor receptor 3 (FGF3) causes it to be constitutively active. FGF3 inhibits bone growth. Always on = smaller bones.

What are the 4 characteristics that complex traits can demonstrate?

Complex traits demonstrate one or more of the following: • Incomplete penetrance • Variable expressivity • Heterogeneity • Presence of phenocopies

What is a gene family?

Composed of genes with high sequence similarity that may carry out similar but distinct functions. >85% similar.

What is the C Terminal Domain? What is the purpose of the C terminal domain? Where is it located?

Definition: Repeated protein sequence at the c-terminus of the RNA poly II protein that can be reversibly phosphorylated. Purpose: binds to proteins that regulate elongation and processing of the RNA transcript. Involved in regular RNA poly activity.

What is the proposed reason for the specific distribution of mutations among differing populations?

Confers some form of genetic advantage. (Sickle Cell and Malaria)

How does Azithromycin affect the bacterial ribosome and not the host eukaryotic ribosome?

Conformation of bacterial and eukaryotic ribosomes are different. Azithromycin is a "constipator" in that it blocks the exit channel of ONLY the bacterial ribosomes.

What is the difference between a constitutional genome and an acquired genome?

Constitutional - your genome since embryo. Acquired - the genome that has been mutated or altered since

What does angiotensin converting enzyme (ACE) do? How does this relate to protease activity?

Constricts blood vessels, BP up. ACE - Converts angiogtensin 1 to angiotensin 2. Angiotensin 2 then proceeds to trigger Blood Vessel constriction. In addition, ACE proteolytically degrades factors involved in vasodilation. Elevated BP medication targets ACE (ACE inhibitor) to help lower BP.

Describe a gap junction

Continuous channels between adjacent cells. Promote rapid communication between epithelial cells, through diffusion of ions and small molecules.

Explain the structure and function of the different types of capillaries as well as where they are found in the body.

Continuous, Fenestrated, and Discontinuous Continuous - continuous epithelial lining, but transfer can occur across lining via pinocytosis Fenestrated - open pores in the epithelium. permit bulk flow of plasma. Discontinuous - large separations (Pores) between endothelia. RBC can pass through. Locations in the body listed on pic.

Describe a particular human disorder that arises from a mutation in a sequence specific DNA binding protein, explaining how the mutation leads to the disorder.

Craniosynostosis - Overdevelopment of bone in skull in children, early fusion of skull sutures. Homeodomain of MSX2 has a one amino acid substitution, the protein binds DNA more strongly- giving a "gain of function" or "hypermorphic allele". Androgen insensitivity syndrome (AIS)- Androgen insensitivity syndrome. Mutations the DNA binding domain of the androgen receptor (a zinc finger DNA binding protein). This makes the patients less responsive to androgens Waardenburg Syndrome type II- deafness, pigmentation anomalies of the eyes, and other pigmentation defects (hair, skin). Mutations in a bHLH DNA binding protein (MITF). This gene encodes a transcription factor that plays a major role in the development of melanocytes

Which GI disease is associated with fistula formation in the GOI tract?

Crohn's

Where in the GI is Crohn's primarily located? Ulcerative Colitis?

Crohn's - Ilium UC - Rectum

What is the treatment for ATD?

Current (these are also for COPD) - Inhalers - bronchodilators - Vx for flu, pneumonia - Pulmonary rehab, O2 - Lung Transplant In Development - ERT - Gene Therapy

What is a CDK? What does it do? How is it related to Cyclin?

Cyclin Dependent Kinase. It is dependent on the binding of cyclin (which is regulated) and the activation (phosphorylation) by CAK to proceed as a kinase. CDK regulates the cell cycle.

Which amino acid is capable of forming disulfide bonds? Why? What type of bond is this? What can this bond do for protein structure?

Cysteine. It bears a sulphur in its sidechain capable of bonding with other sulphur in other cysteine side chains. Bond: Covalent. Protein: Disulfide bonds stabilize both intra-protein (tertiary) and inter-protein (quaternary) structure.

What is the most common life-shortening genetic disease in Caucasians in the United States?

Cystic Fibrosis

What disease adheres to allelic heterogeneity?

Cystic Fibrosis - (ex: 2 different mutations in the same gene still yield CF)

How is Ran-GTP allowed to hydrolyze its bound GTP in the cytoplasm if it is to tightly bound to its cargo to activate its GTPase domain?

Cytoplasmic nucleoporin-associated RanBP1 relieves tight binding, allows RanGAP1 to activate Ran's intrinsic GTPase activity. Both are anchored to cytoplasmic barrier nups

What are the polar negative Amino Acids?

DE Aspartate - D Glutamate - E

What gene is mutated in MD? On which chromosome is it located?

DMPK Chr 19

Southern Blot involves the transfer of what genetic material onto a membrane?

DNA

What enzyme seals the 'nick' in the DNA backbone between the last dNTP addition of DNA pol I and the first dNTP addition by DNA pol III in DNA replication?

DNA Ligase.

What DNA polymerase(s) has 3' -> 5' exonuclease activity?

DNA Pol I and DNA Pol III both used in proofreading.

How is the excised site repaired in BER?

DNA Pol ß and DNA ligase.

Which Enzyme acts to elongate DNA in replication?

DNA Polymerase III

What enzyme in eukaryotes synthesizes an RNA primer where DNA replication initiates.

DNA Primase

What are some cellular abnormalities that signal p53 activity?

DNA damage Cell Cycle Abnormalities Hypoxia

What is the pathway by which p53 is signaled in DNA damage? What does it do?

DNA damage Recruits/activates -> ATM/ATR which phosphorylates (activates) CHK2/CHK1 -> ATR/CHK2/CHK1 act to amplify signal, and phosphorylate p53 (Activate) -> Multiple mechanisms can result (Apoptosis, Cell Cycle regulation, Senescence, DNA repair)

What enzyme removes only the base in BER repair?

DNA glycosylase

What is the complete mechanism and genetic/molecular cause of Fragile X?

DNA mutation in FMR1 gene causes increase in repeats of a CGG sequence within the FMR1 gene. Increased repeats causes increased methylation (at the cytosines) which silences the FMR1 gene. Less FMR1 = Less FMRP = mental deficiencies and physical abnormalities.

Which polymerase in humans is involved in BER?

DNA pol ß (beta)

What is SRY?

DNA-binding protein (transcription factor) encoded by the SRY gene - male sex determination in humans. SRY is an intronless sex-determining gene on the Y chromosome. Mutations in this gene lead to a range of sex-related disorders with varying effects on an individual's phenotype and genotype.

What is a palindromic sequence

DS sequence that reads the same from 3' -> 5' per strand.

State the principles of mitochondria quality control.

Damaged Mito can't make ATP and release damaging reactive oxygen species. SO, damaged mito can: 1) be fixed by fusing with another mito 2) trigger proteases to degrade misfolded proteins 3) trigger apoptosis if damage is extensive

What drug is used to reverse the effects of anesthesia-induced MH attack?

Dantrolene - interacts specifically with the mutant Ryanodine receptor, blocking the outflow of Ca into the intercellular space.

What happens when you decrease the density of Na+ ion channels in a certain section of an axon?

Decreased ability to transmit AP to subsequent section of axon. Slower depolarization of the section -> increased accommodation. Some inactivation channels closing -> Lower AP peak If density gets low enough -> No AP and no AP conduction to subsequent section. This is how some anesthetic works.

What is the overall purpose of siRNA?

Defense/Immunity

What are two learning abnormalities in turner syndrome?

Difficulty in math Visual spatial skills Low non verbal scores.

What disease is associated with normal HEXA and HEXB enzymatic activity but accumulated GM2? What mechanism causes this?

Disease - Tay-Sachs (AB variant) Specifically - GM2AP deficiency/mutation. Causes no GM2 activation and no degradation of GM2

What is a trinucleotide repeat disorder?

Disease-causing abnormal expansion of a segment of DNA consisting of three or more nucleotides.

What are the characteristics of an X-linked recessive inheritance pattern?

Disease: Males >> Females No Male to Male transmission (no x donated to sons) Affected Males -> All daughters are carriers (because they MUST inherit the father's X-chromosome) Carrier (heterozygous) Females -> 1/2 sons affected, 1/2 daughters carriers.

What is Hemoglobin Wayne Disease? What causes it?

Disruption of healthy hemoglobin protein production. Frameshift mutation alters AA sequence. (causes downstream sense mutation)

What is Hemoglobin Constant Spring Disease? What causes it?

Disruption of healthy hemoglobin protein production. Sense mutation causes loss of stop codon. Lengthened protein product.

What are the clinical features of trisomy 21

Distinct facial features, eyes, protruding tongue Hypotonia (low muscle tone) 50% have congenital heart defect 75% have hearing loss 60% with eye problems Degree of mental impairment variable Early onset Alzheimer disease, as adults High prevalence of leukemia in the perinatal period

What characteristic is representative of growing cartilage?

Dividing Chondrocytes stacked into columnar groups

What is the carrier-lipid from which the sugar chain is transferred in N-Linked Glycosylation?

Dolichol.

What is a trait called when one allele exerts its effects over other alleles in the heterozygous state?

Dominant

Explain how nearly all normal p53 activity is diminished in a heterozygous tumor

Dominant negative effect. If even one subunit of mutant p53 is present in the p53 tetramer then it is non functional. Because Mutant p53 is more stable than reg p53, the chances of a WT p53 tetramer in a heterozygote are very slim.

What is the donor in an H-bond? An acceptor?

Donor = -XH group that has internal polarity (i.e the covalently bound H is more electro positive due to its binding to an electro negative element (-CH - no, -NH or - OH yes)) Acceptor - for our purposes usually -O as oxygen is an electro negative factor.

What is uniparental disomy? How does it occur

Double of one parent's haploid contribution to a zygote and zero of the other parent's contribution. Still makes a diploid cell, but depending on the chromosome involved, can result in a disease state. result of a non disjunction event

In regards to DNA damage, which type is most associate with ATM?

Double strand breaks.

What is the ISCN: 46, XY, +21, rob(14;21)? What caused it?

Down Syndrome due to an unbalanced RT.

Where is the 3' UTR located in relation to the primary transcript?

Downstream of the termination codon.

Is the 5' UTR upstream or downstream of the +1 location?

Downstream. It has to be because everything that is in the primary transcript MUST be downstream of +1

Describe the physiological and structural responses to exercise (or lack of exercise) on skeletal muscle (number of cells versus size of cells).

Exercise increases the NUMBER of myofibrils, not the diameter of the individual myofibers. Number of cells stays the same, myofibrils simply reproduce inside.

What is Ibandronate

Drug for treating osteoporosis that has ominous testing protocols.

What are the two muscular dystrophies that we discussed that result from mutations in the same gene? What is the gene? What class of disease related mutation is this? How are they different?

Duchenne' s and Becker's Muscular Dystrophy Both are mutation in Dystrophin (DMD) (gene/protein, same name) Loss of function mutations. x-linked recessive pattern Becker - Mutations that lead to an abnormal version of dystrophin that retains some function Duchenne's - mutations that prevent the production of any functional dystrophin

What can happen if the erasure of methylation/imprinting states fails to occur?

Duplication and loss of specific gene's expression.

What are random segregation and heteroplasmy in regards to mitochondrial inherited disorders?

During cell division mutated Mitochondria and normal mitochondria can end up in different cells. Sometimes the cells will contain NO mutated Mito and be phenotypically normal. Heteroplasmy - this concept.

When is autophagy mostly induced in the cell?

During cellular nutrient stress. Mainly during AA deprivation. Keeps you alive between meals. ALSO right after birth - because you go from having constant nutrient feeding to a periodic, and different feedings.

When are DNA methylation marks established in the genome?

During gameteogenesis.

Where in the human body does all methylation/imprinting become erased?

During gameto-genesis. The start of the proper sex-specific programming. "erase all data" start over.

What does a maintenance methyltransferase do?

During replication, reads methylated DNA (in hemi-methylated state) and methylates newly replicated DNA strand. See pic.

Describe the relationship between 3' end processing of the pre-mRNA and termination of transcription at the end of a gene. What happens to transcription if you alter a Poly A Site?

During transcription, RNA poly II will notice the Polyadenylation site (Marker - AAUAA) which somehow(?) signals the end of transcription and the end of the gene. Mutating a Poly A site results in a loss of proper termination by RNA pol II.

What two proteins are involved in transport of vesicles from the ER to the cis-golgi?

Dyenin and Kinesin

What is the Nernst equation? What it is doing?

E (mV) = RT/zF * ln(Co/Ci) or E = 60/z log (Co/Ci) In human body. where E= equilibrium potential; Co= outside concentration of the ion; Ci= inside concentration; R= gas constant; T= temperature; z= valence of the ion in question; F= Faraday constant. E = Electrical potential difference across the membrane that must exist if the ion is to be at equilibrium given certain concentrations. OR The electrical membrane potential that results when a certain ion is at certain concentrations inside and outside of a cell.

Define reduction potential. What do positive and negative signs mean on the reduction potential value?

E (or ∆E) = measure of readiness that a molecule likes to give/take electrons. Positive value = will take up electrons Negative value = Likes to give them away.

What is Ohms law?

E = IR Electrical potential = Current * Resistance

What are the three ligase enzymes involved in ubiquination? What are their functions?

E1 - Binds and activates Ub E2 - Temporary holder of the Ub (can also directly transfer Ub to protein) E3 - Transfers Ub from E2 to target protein, continues to add Ub to growing Ub chain.

What is the ECF concentration of Na+? The ICF?

ECF - 140 mM ICF - 14 mM

What are the ICF and ECF concentrations of Cl?

ECF - 145 mM ICF - 5 mM Think NaCl in the ECF, and K+ and big anions inside the cell.

What is the ECF concentration of K+? The ICF?

ECF - 5 mM ICF - 145 mM

What eukaryotic elongation factor involved in delivering AA-charged tRNAs to the ribosome can also proofread the tRNA to ensure that it is loaded with the correct AA?

EF1.

Describe an EF hand Domain.

Each EF hand domain has 5 oxygens that associate with the calcium for binding.

Histologically, describe the appearance of Osteons in bone

Each osteon is built around a haversian canal (HC) that contains blood vessels and nerve fibers surrounded by several lamella (L) of bone. The osteocytes occupy compartments (lacunae) between the lamella. Interstitial lamellae (IL) are partially degraded remains of older osteons.

Define Elongation factor

Elongation factors: factors associated with the elongation of a newly synthesized protein. EF2 (elongation factor 2) by way of GTP move the newly made pep.de bond over in the 3' direction exactly one codon. Release factors: proteins that bind to the stop codon can terminate polypep.de synthesis.

What is the difference between an endonuclease and an exonuclease?

Endo - cuts across completed double helix, one side, cuts the backbone. Exo - Chews along the dbl stranded DNA, degrading one side.

Across which membrane of the epithelial cell do exocrine and endocrine glands secrete?

Endocrine - Basolateral Exocrine - Apical

What (more rare) clinical manifestation of VHL affects hearing?

Endolymphatic Sac Tumors - ELST Hearing loss can be an early sign.

What are the primary substances produced by exocrine and endocrine glands?

Exocrine - Mucous and serous secretions Endocrine - Hormones

What is the first law of thermo dynamics?

Energy can be converted into different forms but never created or destroyed.

What is the primary cardiac clinical presentation (diagnosis) of a person with Marfan's syndrome?

Enlarged Aortic root.

Enlarged aortic root is representative of what disease? Aortic Coarctation is representative of what disease? (that we discussed in unit 2)

Enlarged Root - Marfan Coarctation - Turner

What other toxin does the Cholera toxin almost exactly mimic?

Enterotoxin

What is a phenocopy?

Environmentally caused phenotype that mimics the genetic version of the trait.

What are the screening methods for TS?

Enzymatic activity testing. - Testing HexA and HexB activity.

What is the name of the enzyme that methylates C? What is the product of methylation of C?

Enzyme - DNA methyltransferase Product - 5-meC

Describe Enzymatic Covalent catalysis

Enzyme covalently bonds the intermediate state of a reaction. Enzyme returns to start position at the end.

What general enzymatic characteristic is kcat/Km describing?

Enzyme efficiency.

Explain the cause for the RanGDP/GTP gradient and how it contributes to vectorial transport through NPC

Enzymes associated with cytoplasmic FG Nups help RanGTP -> RanGDP immediately outside of the nucleus. Enzymes that reload RanGDP with GTP immediately inside of nucleus => more RanGDP outside and more Ran GTP inside. This maintains the unidirectional flow of RanGDP/GTP in opposite directions along with Ran's bound facilitator proteins.

Why do enzymes have the given Km that they do?

Enzymes have evolved to where the Km they possess is tailored to the substrate concentration in vivo. In other words, enzymes are typically reacting at a rate of 1/2 their maximum in the human body.

What is EGFR?

Epidermal Growth Factor is an RTK. Promotes cell growth and other cancerous conditions. Mutated to be constitutively on in many cancers.

Under the influence of testosterone, the mesonephric ducts become what?

Epidymis Seminal vesicles Vas deferens

True or False Activation of Adenyl Cyclase, and subsequent up regulation of cAMP leads to decreased heart rate and contraction force, lowering BP

FALSE AC on -> inc heart rate and inc force of contraction. Raising BP

What is an example of DNA-binding protein regulation via ligand binding?

Estrogen receptor (ER) binds DNA as a homodimer. However, ER cannot dimerize without estrogen (ligand). Estrogen binds free ER, causes dimerization, recruits co-factors (HAT) acts as transcription activator -> transcription.

What is an example of an intercolating dye that is used to image DNA?

Ethidium Bromide.

What are the names for the heat shock proteins in Eukaryotes and prokaryotes? Why are they triggered? How do they function?

Eukaryotes: Hsp70/Hsp40 Prokaryotes: DnaK/DnaJ Trigger: cellular temp rises, risk denature of proteins, unfolded proteins risk aggregation, chaperones sent out to assist in folding. Mechanism - bind hydrophobic regions (that want to aggregate) and allows protein to attempt to refold correctly.

Describe a mechanism by which the DNA binding activity of a sequence specific DNA binding protein can be inhibited.

Example: Id protein - heterodimerizes with functional HLH proteins. This blocks the HLH protein from DNA binding.

What three methods of excision repair are used to fix damaged, mispaired, or incorrect bases?

Excision: cut in area of lesion and repair BER - Base excision, damage does NOT distort DNA NER - Nucleotide Excision, Damage distorts DNA MMR - Mismatched repair. Misincorporated nucleotides in DNA replication.

What is EC coupling in skeletal muscle contraction?

Excitation-contraction coupling. The mechanism of the AP in the membrane being translated into Ca release from the SR. Parts of this are still not completely understood, though there are theories.

Describe at least three mechanisms for signal termination

Extra cellular signaling molecule Desensitization of Receptors Destruction, switching off, or export of 2nd messengers Phosphorylation/dephosphorylation Protein Binding

Histologically, describe the appearance of tendon

Extremely dense ECM consisting of mostly type 1 collagen fibers with intermingled fibroblasts.

What is the most common mutation in CF?

F508Del Deletion of a Phenylalanine at AA position 508

True or False Actin monomers will spontaneously assemble (nucleate)

FALSE

True or False The heme group is covalently linked to the hemoglobin chain

FALSE

True or False Proteasome-ic cleavage of peptides utilizes ATP

FALSE

True or False X inactivation can occur without XIST.

FALSE

True or False The A, H, and I bands all change length in muscle contraction.

FALSE A line does not change (myosin length not changing) I line DOES change (grows smaller as muscle contracts) H line DOES change (Grows smaller as muscle contracts)

True or False You need a mutation in both the TSC1 and TSC2 genes to cause TSC

FALSE A mutation in either causes TSC. Locus Heterogeneity

What is Fibrodysplasia ossificans progressiva? What is its mechanism?

FOP - Very rare connective tissue disease which causes fibrous tissue (including muscle, tendon, and ligament) to be ossified spontaneously or when damaged. In many cases, injuries can cause joints to become permanently frozen in place. Surgical removal of the extra bone growths has been shown to cause the body to "repair" the affected area with more bone. Mechanism - mutation in activin-like kinase 2. Results in lymphocytes overexpressing BMP4, so during immune response lymphocytes arrive at an area and cause ossification of nearby tissues.

What is the FP region of gp-41?

FP (Fusion Peptide) domain - highly hydrophobic region. Buries in protien core or lipid bilayer.

What lysosomal storage disorders did we discuss in Unit 2? What accumulates in each?

Fabry - Gb3 Gaucher's - Glucocerebrosidase Sandhoff - GM2 Tay-Sachs - GM2 Pompe - Glycogen

What are the names of the two synthetic enzymes used to treat Fabry in ERT?

Fabryzyme - Agalsidase beta Replagal - agalsidase alpha

True or False Increased risk of seizure is a symptom of Type 1 OI

False

True or False The vast majority of human cancers are caused by retroviruses

False

True or False In alternate segregation, the centromeres of homologous chromosomes go to the same pole in gamete formation.

False Alternate means that the two homologous centromeres go to OPPOSITE poles in gamete formation.

True or False Fragile X is X-linked Recessive

False X-Linked Dominant

True or False In meiosis 1 the sister chromatids separate.

False, the homologues separate.

True or False BER can only be used to repair the daughter, or newly replicated DNA strand in the duplex.

False. BER can repair either. MMR is used to only repair daughter strand.

True or False. Acetylation of Histone tails causes tighter affinity between histones and DNA.

False. Acetylation of histone tails (by HATs) loosens histone/DNA affinity.

What cancers are autosomal dominantly inherited?

Familial Adenomatous Polyposis (FAP-APC gene) Familial Retinoblastoma (RB gene) Familial Breast and Ovarian Cancer (BRCA1 and BRCA2 genes) Wilms tumor syndromes.

What is faster: DNA replication in a somatic cell or DNA replication in an embryo? Is the speed related to faster/slower DNA polymerases?

Faster in embryo. DNA poly, same in all cells in human body, has one speed. Faster replication possible because the embryonic cells use more initiation sites on the same DNA. Multiple replication machineries functioning simultaneously.

What are the serious, late-signs of Cerebral Edema?

Fixed-dialated pupils, hypertension coupled with bradycardia.

What Gastrointentinal problems are common in DS?

Feeding problems Constipation GERD - Gastro Esophageal Reflux Disease Celiac

What does the ISCN: 47, XX, +21 signify?

Female with Trisomy 21 (extra 21)

Who is at higher risk for developing MS, females or males? By what factor?

Females. 2.4x more likely than males.

Iron Regulation: What protein binds excess free Fe and sequesters it?

Ferritin

What type of collagen links fibrils to one another or to other tissues?

Fibril-associated collagen. (said to be type IX by many sources but said to be type IV in lecture)

What is type 1 collagen?

Fibrillar collagen. Forms large/long fibers called fibrils. It is present in scar tissue, the end product when tissue heals by repair, as well as tendons, ligaments, the endomysium of myofibrils, the organic part of bone, the dermis, the dentin and organ capsules.

What are fibroblasts and what other cells types can they give rise to?

Fibroblasts are cells that make the bulk of the ECM in connective tissue. They can give rise to adipocytes, smooth muscle cells, chondrocytes, and osteoprogenitor cells as well as to more fibroblasts.

What is an example of a protein composed mostly of beta-sheets.

Fibronin - spider webs Pepsin - HIV protease Immunoglobin

What does a fibroblast produce?

Fibrous proteins, proteoglycans and other ECM components.

What are the first signs of Tay-Sachs? What are the advanced Signs?

First: Muscle weakness, startle response at sudden sound Advanced: Loss of voluntary movement - see, hear, swallow Seizure Mental Retardation Vegetative state.

For whom is IVF a better option?

For conditions where pregnancy is contraindicated for the expectant mother such as some aortic aneurysm syndromes or Ehlers Danlos Syndrome Type IV with increased risk for uterine rupture.

What energetic molecule is necessary for translocation of the ribosome? To what protein is this molecule bound?

GTP Bound to incoming EF2

What are the trinucleotide repeats for: Fragile X Huntington's Myotonic Dystrophy

Fragile X: CGG Huntington's: CAG Myotonic Dystrophy: CTG

What X-linked Dominant diseases did we discuses in unit 2?

Fragile X? Fragile X syndrome has traditionally been considered an X-linked dominant condition with variable expressivity and possibly reduced penetrance. However, due to genetic anticipation and X-inactivation in females, the inheritance of Fragile X syndrome does not follow the usual pattern of X-linked dominant inheritance and some scholars have suggested discontinuing labeling X-linked disorders as dominant or recessive

What is a Lisch Nodule?

Freckling in the eye.

What is needed for DNA polymerase to synthesize DNA?

Free 3' end of an RNA primer (laid down by primase) Free dNTPs Template DNA strand.

Protein AA sequences are normally written in what order?

From N terminus (-NH3) to C terminus (-COO)

What amino acid is Q? What AA category is it in?

Glutamine, Polar uncharged.

What is the origin of the envelope membrane surrounding certain virus'?

From the previous host cell. Capsid exocytoses with new envelope made from cell plasma membrane.

How does the number of channels (G) relate to resistance? How does this relate to cellular ionic driving force?

G = 1/R. More channels = less resistance D.F is related to that ion's distance between its E and the cell's Vm. (Vm-E) so.. E = IR I = (Vm-E) * G. So current increase as channels increase or distance between Vm and E increase.

In what phase are the Pre-RCs assembled?

G1

In what cell cycle phase is cell growth regulated?

G1. Can not proceed past restriction point if size is not correct.

What gene is mutated in Fabry disease? What is its protein product that is then deficient?

GLA Alpha-Galactosidase A - an enzyme.

What is the cellular receptor for the Cholera toxin A/B?

GM1 Ganglioside

What is GM2AP?

GM2 associated protein. Acts as an essential activator in the Hexosaminiosidase A enzymatic activity on GM2. Without GM2AP, this rxn does not occur

What is GM2 Ganglioside?

GM2 is a ganglioside synthesized in the brain that is a component of neuronal cell membrane.

What is GWAS and how does it function? How does GWAS function contribute to the 'missing heritability' problem?

GWAS - Genome Wide Association Study - an examination of many common genetic variants in different individuals to see if any variant is associated with a trait. Basically they look at SNPs in people and attempt to associate certain SNPs with the traits (phenotypes) of the host organism. Missing Heritability - the premise that GWAS, which associates SNPs with Traits, is inaccurate in that most of the heritable trait's phenotypic expression is NOT associated with the loci that the SNPs are pointing to.

What is a mahattan plot?

GWAS readout - genomic coordinates along the X-axis, with (basically) number of SNP associations on the Y. Each dot is a SNP. More SNPS in a loci means more association.

What mutated gene and protein are associated with each of the following diseases Gauchers Fabry Fragile X Myotonic Dystrophy

Gauchers - Gene/Protein: Glucocerebrosidase Fabry - Gene: GLA, Protein: Alpha-Galactosidase A Fragile X - Gene/Protein: FMR1 Myotonic Dystrophy - Gene/Protein: DMPK

Mutations in which gene are associated with ATD? What is the gene's affected protein product?

Gene - SERPINA Protein - Alpha 1-Antitrypsin. (AKA SERPINA1)

What does the LOD score signify? What do low and high scores represent?

Genetic Linkage Study: LOD score represents the likelihood that two loci are linked or not. LOD score of 3 or greater is linked and LOD score of less than -2 is considered unlinkage.

What are the present day goals and methods of genetic counseling?

Genetic counseling is a communication process (1) comprehend the medical facts (diagnosis, probable course of the disorder, available management) (2) appreciate the way heredity contributes to the disorder and the risk of recurrence (3) understand the alternatives for dealing with the risk of recurrence, (4) choose a choice of action which seems to them appropriate in view of their risk (5) to make the best possible adjustment to the disorder

Again: What is a genetic linkage study good for? What is a candidate-gene study good for?

Genetic linkage - Uncommon allele, strong affect Candidate Gene - Common risk allele, weak effect.

What are the functions of the following G-Proteins? Gs Gi Gq

Gs - stimulates Adenyl Cyclase -> upreg cAMP Gi - inhibits AC -> downreg cAMP Gq - Stimulates phospholipase C -> upreg Ca+ in cytosol

What is a GWAS?

Genome wide association study. - is an examination of many common genetic variants (SNP) in different individuals to see if any variant is associated with a trait. Comparing cases and controls to see differences (globally) and look for trait association.

What is imprinting?

Genomic imprinting is the epigenetic phenomenon by which certain genes are expressed in a parent-of-origin-specific manner. Sex-dependent epigenetic modulation of regulatory regions.

What is the fate of a DNA methylation pattern for a germ line cell? Somatic cell?

Germ - It is erased and reset. Somatic - It is repeated, maintained, and propagated.

Which Rx is used to treat CML?

Gleevec

What cell in the body has the most negative E?

Glial cells.

What are the two ways in which DNA damage in recognized in NER?

Global NER - anywhere in the genome Transcription-coupled NER - recognized in area of active transcription, stalled RNA poly.

Are actin and myosin fibrous or globular?

Globular. So the meeting of muscle fiber (actin myosin) with tendon (collagen) is the meeting of globular protein with fibrous protein.

What mutation occurs in hemoglobin C disease? What is the cellular presentation of Hemoglobin C disease?

Glu -> Lys at codon 6 of beta globin gene. (the same spot as Sickle cell, just different mutation) Cellular presentation: Similar to Sickle cell in that it causes increased rigidity in the cell.

What electrical (charge) alteration to HbA happens in both HbS and HbC?

Glu, which is negative, is changed to Val in HbS and Lys in HbC which are neutral and positive respectively.

Which AA missense mutation is associated with the more severe form of ATD?

Glu342Lys

In regards to post-translational AA modification, how does Vitamin K deficiency contribute to a lack of blood clotting? What is this disease (deficiency) called?

Glutamate -> Carboxyglutamate. Carboxyl group added. Carboxyglutamate is in many proteins involved in blood clotting. The enzyme that adds the carboxyl group requires vitamin K. When vit K deficient, carboxyglutamate deficient, clotting impaired. Called Warfarin Syndrome.

What is the AA residue mutation in Achondroplasia?

Gly380Arg

What AA allows collagen triple helix to pack so tightly? why?

Glycine. no sidechain. allows for tight turns and close packing.

What are GAGs? By what mechanism do they generate a gelatinous matrix?

Glycosaminoglycans (GAG) are long polymers (100s - 1000s of sugars) of carbohydrate molecules (polysaccharides). GAGs are high negatively charged. Water associates with negative charge. Highly hydrated. Generates gelatinous surrounding. Their rigid extended structure supports gel matrix.

Why do 45, X patients have Primary Amenorrhea?

Gonadal Dysgenesis - no ovaries. so no periods.

What is a common physical test for children with suspected Duchenne's MD?

Gowers Maneuver Child can not just stand up from supine. Must roll over and 'walk' themselves to upright.

What is Grb2? What does it do? How does it lead to Ras activation?

Grb2 Recognizes the intercellular, tyrosine-phosphorylated domain of an RTK. Acts as an adapter that binds Sos (a GEF) which in turn loads Ras with a GTP -> Activates Ras.

How long are lncRNA?

Greater than 200nt

What are the names of the Chaperonin proteins in E.Coli? Which is the body and which is the cap? Describe the structure.

GroEL/GroES. GroEL - heptameter of these makes up the body GroES - Cap that fits on end of heptamer.

Define promotor proximal element

Group of 8-10bp long sequences within 200bp upstream of transcriptional start site. Trans acting factors bind. If they get too far away they cease to work

Describe the RB cell cycle regulation pathway, all proteins involved, and post translational modification.

Growth factor binds to receptors on outside of cell -> activates CDK 4,6/cycD1-3 -> Activates CDK2/cycE -> Phosphorylation of RB -> Allows cell to enter S phase from G phase.

Which G protein stimulates cAMP production? Which inhibits it?

Gs - stimulates Gi - inhibits

TS patients usually have a mutation in what gene?

HEXA - Both alleles

What are the two subunits of Hexosaminidase A?

HEXA and HEXB Hexosaminidase A is a heterodimer composed of an alpha subunit and a beta subunit. The alpha subunit polypeptide is encoded by the HEXA gene while the beta subunit is encoded by the HEXB gene.

What is HIF-a? What is the full mechanism of VHL and its relation to HIF-a?

HIF-a - acts to activate genes involved in cancer cell growth. Normoxic - HIF-a is hydroxylated by other enzymes -> VHL protein adds Ub to HIF-a -> HIF-a it is degraded. Hypoxic - HIF-a NOT hydroxylated -> No Ub by VHL -> HIF-a accumulates and turns on genes involved in cancer growth. When VHL is mutated, Cell and HIF-a act as though cell is in hypoxic conditions.

What are the polar positive Amino Acids?

HKR His Kids Reek Histidine - H Lysine - K Arginine - R

What gene has the strongest association with Multiple Sclerosis?

HLA-DRB1 - about 30% of all cases.

Who has higher HbF levels - HPFH or δβ0-thalassemia individuals?

HPFH individuals have higher HbF (17-35%) level than δβ0-thalassemia individuals (5-18%). (increased gamma-globin production)

If exogenous DS damage occurs when the cell is in G2 phase, which type of dsDNA repair is used?

HR, because again, the site chromatid is present.

If exogenous DS damage occurs when the cell is in S phase, which type of dsDNA repair is used?

HR, because again, the site chromatid is present.

Between NHEJ and HR, which is used for the repair of DS breaks in DNA replication damage?

HR, because the sister chromatid is present.

What gene is mutated in HD? What is its protein product? What does that protein do?

HTT gene Huntingtin protein Function of protein largely unknown

Histology: What are two dyes discussed and what do they bind .

Haematoxylin and Eosin (H&E): - Haematoxylin - binds acidic and negatively charged substances (DNA, RNA) - Eosin - bind positively charged AAs (Lysine, Arginine) Periodic/Acid/Schiff (PAS): Binds carbohydrates such as glycogen

What is a haplotype?

Haplotype - a set of DNA variations, or polymorphisms, that tend to be inherited together from one parent. Each parent donates their own haplotype (haploid cells) to a child.

How does lncRNA regulate miRNA?

Has same recognition sites on target mRNA as miRNA. Competitively binds and blocks miRNA activity. Can be protective in this way from cleavage and degradation of mRNA.

How can gel electrophoresis test for HbS and HbC?

HbA has more neg charge (Glutamate), will migrate more towards cathode. HbS and HbC are less negative and will migrate less. Visible against control HbA which is which. Pic - (protein gel) Cathode (+) is at bottom.

What is more soluble in blood, HbA or HbS?

HbA. Hbs insolubility causes the disease state.

Which genotype has malaria resistance?

HbA/HbS - AKA Sickle Cell Trait

What are the three Hemoglobinopathies discussed that are point mutations in the b-globin gene?

HbS - Sickle Cell - codon 6 HbC - Hemoglobin C - same codon as SS HbE - codon 25-27 (glutamic acid to lysine)

What is the first step in DNA hybridization? What must you do before adding the hybridization probe? When do you add the probe?

Heat the dsDNA. Melt apart. Must add probe when the DNA solution is still hot and melted apart.

What factors can denature proteins? What is the Tm? How does Tm relate to protein stability?

Heat, pH, Chemicals (organic solvent, urea, guanidinium, detergent) Tm = temperature at which half of all protein is denatured Higher Tm = More stability .

Provide examples of how cilia function in development and tissue homeostasis.

Hedgehog signaling

Protein sidechains lack affinity for O2. So how then does the body reversibly bind and transport oxygen?

Heme groups in Myoglobin and Hemoglobin contain Iron (Fe). Transition metals such as iron have affinity for O2, but are easily oxidized to their non-binding form (Fe2+ -> Fe3+). Burying heme group and O2 inside a protein guards it from oxidation and allows Fe to remain in its oxygen-binding state (Fe2+)

What is the predominant oxygen transporting molecule in the human blood stream?

Hemoglobin

What molecule is useful for transport to tissues? Why?

Hemoglobin - variable affinity for oxygen. High pO2 = High affinity Low pO2 = Low affinity

At birth what Hemoglobin alterations occur?

Hemoglobin Gamma begins to drop and gives rise to Beta and Delta (eventually Hb beta (97%) and Hb Delta (2%) in adult) HbF -> HbA HbA = 2 alpha and 2 beta subunits.

What is an example of a 'gain of function of protein' disease that we discussed? What is its mechanism?

Hemoglobin Kempsey Missense mutation in hemoglobin, INCREASES O2 affinity of hemoglobin. Hb then does not release O2 at tissues.

What are the two primary globins present immediately following conception?

Hemoglobin Zeta and Epsilon.

What three terms describe the physical appearance of a RBC with alpha or beta thalassemia? What does each mean?

Hemolysis - lyse of RBC Microcytosis - Smaller size, cos less protein production Hypochromia - Paler color of RBC due to less O2 binding

What X-linked Recessive diseases did we discuses in unit 2?

Hemophelia A Duchenne's MD Fabry Beckers MD

What is HPFH?

Hereditary Persistence of Fetal Hemoglobin. Condition in which HbF production continues well into adulthood.

What type of chromatin is localized near the centromere?

Heterochromatin. Tightly packed, structural region.

True or False SB-zero Thalassemia individuals still produce a fair amount of B-globin

TRUE But it is HbS. The B-zero allele makes little to none. The S allele makes misfolded b-globin AKA HbS

What ethnic groups/populations have the highest risk of MS?

Highest - White caucasians, northern europeans. Lowest Risk - Asian, African.

Describe a tight junction

Highly selective barrier that limits or prevents diffusion of substances between epithelial cells and through the epithelial layer.

What is the function of Mast cells in inflammation and defense?

Histamine secreted by mast cells is thought to promote endothelial permeabilization (causing swelling), and also can signal long distance to hematopoietic tissue to stimulate productions of more white blood cells, which are recruited form the blood stream at the site of inflammation.

Which amino acid is most seen in active sites of proteins? Why?

Histidine Its pKa = 6.5. Close to physiological pH (7.4) so can exist in protonated and deprotonated form depending on environment. Reactive.

What are the two histone acetyl-modifiers that we discussed? How do they function? What aspect of the histone do they alter?

Histone acetyltransferases (HATS)- acetylate N-termini (tails) of histones. Neutralize + chg of histone. Less electrostatic affinity for DNA (- chg). Loosen. More access to DNA Histone deacetylases (HDACs)- DEacetylate N-termini (tails) of histones. Stabilize + chg of histone. MORE electrostatic affinity for DNA (- chg). Tighten DNA-histone affinity.

What anesthetic drugs cause MH?

Holothane - inhaled general anesthetic Succinylcholine - causes conscious muscular paralysis, used to initiate tracheal intubation.

What is the difference between a homologous and non-homologous Robertsonian translocation (RT)?

Homologous - acrocentric homologues fuse at centromere. (EX: 13-13) Non-Homolous - acrocentric non-homologues fuse at centromere. (EX: 13-14)

What is meant by the terms homozygous, heterozygous, and hemizygous?

Homozygous - the two alleles are identical at a certain locus Heterozygous - the two alleles are different at a given locus Hemizygous - (mostly in reference to males) XY, in reference to the singular characteristic to the X and Y chromosome.

Ribosomal subunit joining in prokaryotes and eukaryotes involves what energetic molecule?

Hydrolysis of GTP.

What does hexosaminidase A do?

Hydrolyzes GM2 gangliosides.

If proper match between incoming tRNA and codon is achieved what happens to EF1a?

Hydrolyzes its GTP, departs.

How do the FG repeats contribute to nuclear transport?

Hydrophobic areas on surface of proteins associate with the FG repeats, are passed from FG region to FG region of all the barrier nucleoporins till it reaches nucleus.

What modified AA is present in collagen and essential to its structure? Where is collagen found?

Hydroxyproline Tendons, cartilage, etc

What are the clinical definitions/diagnosis of DKA?

Hyperglycemia - Plasma glucose >200 mg/dL Metabolic acidosis - Venous pH < 7.3 and/or HCO3- < 15 mmol/L Ketonemia and ketonuria

If a cell contains 300mM of a protein in the ICF and the ECF that the cell is introduced to contains 300mM of NaCl (to which the cell membrane is NOT permeable)...is the solution: Hyper/iso/Hypotonic? Hyper/iso/Hypo-osmotic? And what happens to the cell in terms of volume?

Hyperosmotic - NaCl has two particles per mole, so 300mM = 600mosM Hypertonic - because ECF is higher in osmoles, water leaves the cell Cell shrinks.

What does the protein Argonaut do.

I mean....see the pic. I have no idea what the take away is here. Perhaps that Argonaut binds small silencing RNA and selects the one side of the dsRNA for use.

How can karyopherins contribute to cancer phenotypes?

If gene is mutated (such as in Crm1) it can be upregulated and can overly export proteins not needing export from nucleus. Leads to overexpression phenotype of genes facilitated by karyopherin

Once the miRISC complex is formed what does it do in regards to mRNA and translation?

If the miRNA of the miRISC complementarily matches its target mRNA, that target mRNA is cleaved and degraded. If it is NOT a perfect match, leads to translational repression.

What is an acrocentric chromosome?

If the p (short) arm is so short that it is hard to observe, but still present, then the chromosome is acrocentric.

What is the function of Rapamycin/Sirolimus? And what is the mTOR pathway?

Immunosuppressive, blocks activation of T and B cells. (blocks the G1 -> S phase transition). mTOR - mechanistic Target of Rapmycin - MTOR is a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. Basically mTOR seems to regulate cell cycle in a positive manner, allowing entry into S phase and rapamycin blocks that transition. Rapamycin used heavily in organ transplants, block body's immune reaction to new organ.

What is meant by an 'imprinted' chromosome?

Imprinting - the epigenetic phenomenon by which certain genes are expressed in a parent-of-origin-specific manner. If the allele inherited from the father is imprinted, it is thereby silenced, and only the allele from the mother is expressed. If the allele from the mother is imprinted, then only the allele from the father is expressed. Imprinting = silencing

How does the MMR recognize daughter and mother strand?

In E.Coli - Methylation state. mother strand is heavily methylated. New strand is not, uses that for recognition. In Eukaryotes - Theory: Frequent nicks, such as in lagging strand, show which is new/old. Largely unsure how this works in regards to leading strand.

Describe the appearance of endochondral ossification histologically.

In forming bones, cartilage can easily be identified by chains of dividing chondrocytes (circled) and by chondrocyte hypertrophy (CH), signifying the interstitial growth of cartilage. The region of bone (B) can be identified by the slightly darker stained regions juxtaposed to cartilage (C), and by convoluted spaces within that contains bone marrow (BM). Bone areas contain osteocytes that den be seen in the (B) areas spread out from one another as they sit in their pockets in the bone matrix.

When in Meiosis did a non-disjunction event occur if you have 2 (n+1) gametes and 2 (n-1) gametes?

In meiosis I 100% abnormal.

Is human DNA replicated starting in one location? How does it proceed?

In some cases 100 of origins used simultaneously in order to replicate human genome. Proceeds outward in both directions from each replication origin. Number of origins used simultaneously is regulated in cell cycle

Where is the anti-Shine Delgarno sequence?

In the 30S ribosomal subunit. (Prokaryotes right? Cos there is no 30S in Eukaryotes)

Where is the initiation codon for translation generally located (in relation to transcription)?

In the first exon of the primary transcript.

Is CDK largely active or inactive in G1?

Inactive. Allowing Pre-RCs to assemble.

Which class of penetrance is associated with complex traits

Incomplete penetrance - some with genotype will not get trait. As opposed to complete penetrance (all who have genotype get trait) which more follow typical mendelian inheritance patterns.

What is the function of HSP60?

Incorrectly folded proteins bind interior, hydrophobic walls of HSP60, relaxes protein folding, allows to refold in new conformation.

What other issues result from the myocardium disarray and what do they cause clinically?

Increasing fibrosis between disarrayed myocardial cells - Causes arrhythmia in heart rate because this fibrosis messes with normal AP conduction through the myocardial cells. Dysplastic intramyocardial arterioles - Basically erratic angiogenesis and vascular development within the heart muscle. Can cause ischemia in parts of the heart due to loss of blood flow.

Is TD1 increasing or decreasing each year? At what rate?

Increasing, 3-5%

What are the 4 stages of translation? Which is the most different between pro and eukaryotes?

Initiation - getting the machinery assembled in the right place and thus setting the reading frame (MOST DIFFERENT between prokaryotes and eukaryotes) Elongation - moving along the mRNA and making the encoded protein Termination - reading a stop codon at the end of the sequence, ending elongation, and dissociating the subunits Recycling - getting the ribosomal subunits ready to be used again

Hexokinase when binding its substrate exhibits what confirmational change?

Induced Fit, the enzyme alters its conformation.

What are the challenges across the life span of a 45, X patient?

Infertility Short Stature Sexual Development Concerns about health and aging.

Does an influx or an efflux of Ca into the cytosol of SA node cells cause in increase in heart rate?

Influx.

What are the three general classes of RNA? Which RNAs are in each category?

Information Containing: Ex. mRNA Structural: Ex tRNA, rRNA, snRNA, snoRNA Regulatory: Ex. miRNA, siRNA, lncRNA

What is the difference between Inherited and Sporadic retinoblastoma? What is the clinical presentation and when?

Inherited - mutation in germline coupled with new somatic mutation. LOH -> Phenotype Onset: Early Tumors: Multiple (cos mutation in germline) Sporadic - 2 new somatic mutations Onset: Later Tumors: Single (cos mutation in somatic dividing cell only)

What is the diagnostic difference between inherited VHL and sporadic VHL?

Inherited - one VHL-associated tumor AND positive family history Sporadic - two VHL-associated tumors.

A patient presents with bilateral RB. Is their disease inherited or sporadic?

Inherited. Multiple tumors. (Pic is unilateral)

Is the retinoblastoma (Rb) protein an inhibitor or activator of the cell cycle? What is the mechanism? What regulates Rb?

Inhibitor. When mutated (in retinoblastomas) uncontrolled proliferation. Mechanism: Rb binds and inhibits E2F, a transcription factor that promotes many DNA replication pathways. So no S cycle. CDKs regulate Rb.

At which point is specificity regulated in viral membrane fusion?

Initial activation of the binding complex (antiparallel a-helix proteins). (pre-fusion in pic)

Which are more numerous (bp) in the pre-mature RNA, introns or exons?

Introns, non translated material. 'Exons in a sea of introns'

What is the mechanism of Hemophilia A?

Inversion on the x-chromosome involves large segment of F8 gene -> F8 gene severely mutated -> no F8 clotting factor -> excessive bleeding, no clotting.

What are the ways in which Ca can move into the cytoplasm from source areas?

Ion Channels Voltage/Ligand gated Ca channels IP3/ryanodine receptors in ER/SR (from ER/SR into cytoplasm) Mitochondrial uniporter

Iron Regulation: What do the Iron Response Binding Proteins do? Where do they bind?

Iron Response Binding Proteins - Fe regulated RNA binding protein that guards ferritin and TFR gene from degradation. IRE-BP bound to IRE - upregulates ferritin and Transferrin Receptor (TFR) via guarding mRNA from degradation. High Fe - Fe bound to IRE-BP, IRE-BP can not bind IRE. Lower levels of Transferrin and TFR co mRNA gets degraded. Low Fe - Fe NOT Bound to IRE-BP, IRE-BP Binds to IRE. Higher levels of Transferring and TFR cos mRNA is protected from degradation.

Iron Regulation: What is an IRE?

Iron Response Element - loop feature in RNA that Iron Response Binding proteins can bind to.

True or False In all cases the coat proteins must dissociate from the vesicle after budding in order for the vesicle to fuse with another membrane

TRUE Coat proteins block membrane fusion.

What is the function of a 'kinase'?

It Phosphorylates target factors.

In what way is type 1 diabetes a complex trait?

It adheres to incomplete penetrance in that more people have the genetic mutation than present with the illness.

What results when a cytosine becomes methylated and then deaminated?

It becomes a Thymine.

How does alpha-amanitin function to halt translation?

It doesn't. it blocks TRANSCRIPTION. just making sure you're paying attention. :) It binds to the Bridge Helix of RNA poly, prevents RNA chain elongation.

What is the most notable feature of connective tissue (CT)?

It forms an extra cellular matrix around the CT cells.

What is DUF 1220 and why is it so exciting?

It is a protein domain of unknown function that shows a striking human lineage-specific (HLS) increase in copy number and may be important to human brain evolution. The copy number of DUF1220 domains increases generally as a function of a species evolutionary proximity to humans. DUF1220 copy number is highest in human (over 270, with some person-to-person variations). and shows the largest HLS increase in copy number (an additional 160 copies) of any protein coding region in the human genome. Laymans? Seems to be the primary protein encoding region of the genome that drastically sets us apart from our closest species relatives. The more DUF1220 you have the higher your level of brain development. Seems to be a correlation that could be utilized.

What is ubiqutin (Ub)? What does it do when added to a protein?

It is a protein ~ 76AA in length. It signals a protein to be degraded when adhered to it.

From which cells is the highest resolution for karyotypes achieved?

Leukocytes (WBC) from peripheral blood.

What is Cooley's Anemia?

Its Beta-Thalassemia Major.

Why is smooth muscle called smooth muscle?

Its not visibly striated.

DNA-PKcs is a protein kinase. What is its phosphorylation target? What does that do?

Itself. Allows for the recruitment of Artemis

What are the mechanisms of Ivacaftor and Lumacaftor in CF treatment? Which type of CF does each treat?

Ivacaftor - Increases Cl transport through CFTR. (Type III CF, gating issue) Lumacaftor - Acts on ΔF508 CFTR during protein folding and suppresses misfolding (Type II CF).

What is the Kd of a protein ligand binding reaction?

Kd = the point at which 1/2 of the protein present has bound ligands.

What is an example of a mitochondrially inherited disorder?

Kearns-Sayre Syndrome MELAS MERRF Leber Hereditary Optic Neuropathy

What is an example of a fibrous protein composed almost entirely of Alpha-helices?

Keratin Myosin Tropomyocin Fibrinogen

What direction does Kinesin move along the MT? Dyenin?

Kinesin - Toward plus end, or outwards Dynein - Toward minus end, or inwards.

Which direction along the cilia do dynein and kinesin travel?

Kinesin - Towards the tip (+ end) Dynein - Towards the basal bodies (-end)

What is 47, XXY called? What are clinical presentations?

Klinefelter Syndrome 1) Relatively common 2) Not lethal in utero 3) Tall 4) Infertile, hypogonadism 5) Underdevelopment of secondary sexual characteristics 6) Learning disabilities

How does the [I] of a non-competitive inhibitor affect kcat and Km?

Km - Altered. the non competitive inhibitor usually alters the active site and alters its interaction with the substrate. kcat - Affected. Since the active site (enzyme) is altered it alters its 'speed'

Which protein recognizes DS breaks in NHEJ? What does it do?

Ku - recognition and recruitment of DNA-PKcs

The amino acids in all proteins are which isomer?

L- Isomer

Describe cholesterol absorption by the cell

LDL binds LD receptor on cell surface, is bound and endocytosed, pH in endosome drops, LDL released from receptor, cholesterol continues on to lysosome, LDL receptor recycled to cell surface.

What is a LINE? What percentage of the human genome do they occupy?

LINE - Long Interspersed Nuclear Elements are retrotransposons that have accumulated to very high copy numbers in many mammalian genomes. 20% of the human genome.

Diagram the GTP-hydrolysis cycle of G protein signaling.

Ligand binds GPCR -> G-alpha swaps GDP for GTP -> signals downstream effectors until G-protein hydrolyzes its own GTP to GDP.

Give on example of why a cell would go to G0 phase.

Lack of nutrients.

To which strand (leading, lagging) is telomerase adding coding repeats (telomeres)? Which enzyme adds to the parent strand? Which adds to the new strand?

Lagging - site of end replication problem Telomerase - extends the parent strand DNA Polymerase/Primase - Primer laid down as usual and lagging is extended back in the 5'->3' direction towards rest of new DNA strand.

Describe the basic structure of a Kinase

Large and small lobes, ATP binding area between lobes. When Kinase in closed position the gly-rich loop of the small lobe pushes ATP close to substrate. Open conformation allows exchange of ADP for new ATP. Thus kinase activity is thought to require alternating open and closed conformations

Histologically, describe the appearance of Osteoclasts

Large multi-nucleated cells sitting on bone surface.

In which subunit of the ribosome does the chemistry of polypeptide elongation occur?

Large subunit

What is the psi bond? What is the phi bond?

Layman's terms. These never refer to the peptide bond! Psi - The bond between an AA's two carbons in backbone Phi - The bond between an AA's alpha carbon and its own nitrogen in backbone Think 'psi' sounds like 'sci', sort of a 'c' sound to it. This is the bond between C's. (sry, best I could do :) )

What affects DNA melting temperature aside from [salt] and pH?

Length of DNA - longer = higher Tm. More H-bonds to break [C/G] versus [A/T] - more G/C bonds = more h-bonds = higher Tm.

What is the general AA characteristic of a classic NES signal?

Leucine (L) rich region. On surface of protein. Easy to be recognized.

Which class of transcription factor dimerize through their single alpha helical domain?

Leucine Zipper.

In regards to protein structure, what are the lock and key and Induced fit models?

Lock and Key - protein has a specific structure that will fit only very specific substrates Induced Fit - when protein and substrate come together there is a conformational change

What is an LCR? How does it contribute to Hb expression patterns?

Locus Control Region - a long-range cis-regulatory element that enhances expression of linked genes downstream. In the case of Hb subunits, it regulates their expression based on distance to the gene. It is thought that this is why epsilon is expressed before gamma which is expressed before delta, etc... The distances are greater.

Describe the basis and functional consequences of connective tissue diversity.

Loose Connective Tissue - Sparse collagen fibrils, High cell density and ground substance, Blood and lymph capillaries abundant, nerves abundant. Lose CT is important in inflammation and would healing. Dense CT - Thick collagen fibrils that are very abundant relative to ground substance. Low cell density. great strength, resist strong shear forces in particular directions, such as in tendons and ligaments.

How does LOH contribute to RB?

Loss of Heterozygosity process results in the development of a cell that has homozygous deletions of the RB gene. Cells in the eye differentiate and stop diving early, the RB-deletion cell does not. Immortal. Produces tumor.

What is deamination?

Loss of an amine group from a nitrogenous base of a nucleotide.

What are two abnormalities of the neck in turner syndrome?

Low posterior hairline Webbing - webbed neck

Explain transfusion and iron-chelation as a severe a-thalassemia treatment

Low to no a-globin. Replace blood with healthy blood, however, iron accumulation from repeated transfusion leads to organ failure. Iron chelation therapy (e.g. desferrioxamine) is used to reduce the complications of iron overload.

What are the treatments for PKU?

Low-phenylalanine diet - (no protein rich foods) BH4 supplementation Gene therapy ERT

What are all of the major features of TSC?

Major: (mostly bumps/growths/benign tumors..) Angiofibromas - non-fluid filled skin bumps Cardiac rhabdomyoma - benign heart tumor, infants Cortical dysplasias - failure of cranial neurons to migrate properly Hypomelanotic macules - light patches of skin Lymphangioleiomyomatosis - cystic lung destruction Multiple retinal nodular hamartomas - benign tumor-like nodules Renal angiomyolipoma - benign nodule Shagreen Patch - orange peel skin patch Subependymal nodule - nodule in CNS SEGA - Nodule in CNS Ungual Fibroma - Nodule on/around nailbed

What results when cytosine becomes deaminated?

Makes Uracil.

Medical Outcomes How does a sexually ambiguous male baby respond to testosterone treatment? And a sexually ambiguous female respond to estrogen?

Male - Little to no response to testosterone. Female - Response to estrogen. At least in secondary sex characteristics.

What does ISCN: 46, XY mean?

Male with normal amount of chromosomes. 44 autosomal and 2 sex

What disease is associated with mutated RYR1?

Malignant Hyperthermia Reaction to voltile anesthetics. The anesthetic alters the SR Ca+2 release channel such that Ca+2 release occurs without its normal requirement for a conformational change in the DHP receptor. The steady Ca+2 leak from the SR activates the Ca+2 ATPase to pump Ca+2 back into the SR and a futile, heat-producing cycle occurs and is lethal if not corrected.

What is a retinoblastoma?

Malignant tumor of the retina.

How is the brain/blood osmolality problem resolved in common therapy?

Mannitol into blood. Introduction of osmols into blood Must be acutely given or body may uptake mannitol and start to rebalance osmolality. Has rapid results.

What sugar chain, when added to added to a protein, signals it for lysosomal degradation? Where does this addition occur?

Mannose-6 phosphate In the Golgi

Histologically, describe the appearance of mast cells

Many granules in the cytoplasm containing pro inflammatory, allergic and vascular response factors.

What is polymorphism?

Mutations in non-essential AA in protein that still result in functional protein. Variation within a population of healthy proteins. Non-essential means not necessary for active sites, structure, function, etc..... Ex: Diff hair and eye color. Skin Color...etc

What mutated gene and protein are associated with each of the following diseases Marfans Huntingtons Myotonic Dystrophy

Marfans - Gene: FBN1, Protein: Fibrillin Huntingtons - Gene: HTT, Protein: Huntingtin Myotonic Dystrophy - Gene/Protein: DMPK

What are some methods for regulating cargo binding to importins/exportins

Masking, affinity enhancement, and alternate exposure of NLS/NES on same protein.

What is the difference between the mechanisms of microautophagy and macroautophagy?

Micro - the direct engulfment of cytoplasmic material into the lysosome Macro - Macroautophagy is the main pathway, used primarily to eradicate damaged cell organelles or unused proteins. This involves the formation of a double membrane known as an autophagosome, about the organelle marked for destruction. The autophagosome then travels through the cytoplasm of the cell to a lysosome, and the two organelles fuse. Contents degraded.

What is the difference between monozygotic and dizygotic twins?

Monozygotic - twins from one zygote that separated into independently growing cell aggregations giving rise to two individuals of the same sex and identical genetic constitution. Dizygotic - Usually occur when two fertilized eggs are implanted in the uterus wall at the same time. When two eggs are independently fertilized by two different sperm cells, fraternal twins result. Basically like regular siblings born at the same time.

Why is venous blood lower pH than arterial blood?

More CO2 in venous blood. Dissolved CO2 reacts with water to make carbonic acid which dissociated into bicarbonate and protons (H+) CO2 + H2O <-(catalyzed by carbonic anhydrase)-> H2CO3 <-> H+ + HCO3-

Describe the mechanism of variable Hemoglobin O2 affinity

More O2 bound to Hemoglobin protein subunits = more affinity for O2 by the central heme group. and Vice versa. O2 binding to subunits alters hemoglobin quaternary structure. Conformation of structure alters O2 affinity overall.

Are there more Phosphatases or Kinases in the body?

More than 3x more kinases. Means that phosphatases are less specific in the kinase they oppose.

What does the ISCN: 45, X/46, XX signify?

Mosaicism between two types of cells: 1) Normal Female cells 2) Female cells lacking an X

Where is aneuploidy most common? Where is it least common and why?

Most common - Spontaneous abortions (SAB) Least Common - New borns (babies that survived to term and survived childbirth). Least common in newborns because most babies with chromosome abnormalities die before birth (SAB - 50% 60%) or are stillborn (4-6%).

What is a cardiac rhabdomyoma?

Most common primary tumor of the heart in infants/children. Benign - Lacks capacity for metastasis or invasion. Can either regress, disappear, or remain same size. Usually associated with TSC

Explain the differences between motile and sensory cilia.

Motile cilia: 9+2 MT arrangement. Axonemeal dyenin active in sliding MTs in relation to each other causing movement of the cilia. Sensory: Non-motile. 9+0 MT arrangement. No Axonemal dyenin.

What restriction enzyme is used in Sickle Cell diagnosis?

MstII

What is multifactorial inheritance?

Multifactorial inheritance means that many factors are involved in causing a birth defect. The factors are usually both genetic and environmental, where a combination of genes from both parents, in addition to unknown environmental factors, produce the trait or condition.

What are MEN syndromes? What is their inheritance pattern?

Multiple Endocrine Neoplasia - MEN Tumors of endocrine glands. Multiple syndromes under the MEN classification.

What is pleiotropy? How can it affect normal, observable Mendelian inheritance patterns?

Multiple different phenotypic effects due to mutation(s) in a SINGLE gene. Often used, when the phenotypes are seemingly unrelated and/or in multiple different tissues. Example: Neurofibromatosis Type I leads to: café au lait spots (skin), neurofibromas (peripheral nervous tissue), hammartomas in the eyes (ocular), abnormal freckling (skin again), and learning difficulties (central nervous system). Multiple phenotypes, same single gene. If looking for normal Mendelain pattern, would believe there to be multiple mutated genes, but not the case.

What are the clinical manifestations of Osteogenesis Imperfecta type 1(OI)?

Multiple fractures, frequent, even at birth. Mild Short statures Adult onset hearing loss Blue Sclera

Non related and scary-gross medical trivia: When a patient receives full thickness burns to a large portion of the body the burnt skin completely dies and becomes tough and non-elastic (cooked leather). Swelling of the underlying tissues occurs (due to damage) but due to this external restriction by the dead skin the swelling crushes the insides of the body causing life threatening respiratory and cardiovascular issues. How is this situation treated clinically?

Multiple linear incisions through burnt skin to allow swelling to occur externally and relieve internal pressure. In cases of very deep burns compartment syndrome can also occur and these incisions must proceed to the level of the deep fascia.

What is myostatin? What is its function?

Muscle growth regulator. Normally made and secreted by muscles as a negative feedback for muscle growth. Mutations in myostatin cause muscular growth and strength increase.

What are the clinical signs of MH?

Muscle rigidity - Masseter spasm Increased CO2 production Rhabodomyolysis Hyperthermia

Give an example of a disease that can be treated with antisense oligonucleotide (ASO) therapy and its Mechanism.

Muscular dystrophy - disease related to truncated protein due to nonsense mutation. - ASO (direct injection) introduces new splice sites in formerly truncated gene. Now nonsense mutation is fixed. New splice sites lead to new exon, but this exon translates areas of the final protein product that are non essential. Final protein product is ok, full length. Exon skipping to restore protein function.

Describe Allele-specific PCR

Must know the mutation. Design primer that matches with wild type and a primer that matches with mutant. When primer matches then DNA poly will make a complimentary DNA in PCR. When not primer not match it won't.

Which two proteins in MMR initiate repair mechanism?

MutS and MutH

Describe the full mechanism for Fabry's disease.

Mutation in GLA gene -> less Alpha-galactosidase A -> aggregation of Gb3 sphingolipid -> widespread damages.

Describe the full mechanism of Tay-Sachs

Mutation in HEXA gene (both alleles) => Alpha subunit of Hexosaminidase A mutated => decrease of GM2 degradation => aggregation of G2M2 in Lysosomes of CNS neurons.

Describe the complete molecular mechanism of NFT1

Mutation in NF1 at 17q11.2 -> LOF mutation in Neurofibromin -> phenotype

What is the mechanism for ATD?

Mutation in SERPINA gene => Low Alpha 1 AT => Diminished inhibition of Elastase => increased elastase activity => decreased elastin in pulmonary epithelium => emphysema and lung damage.

What is a Missense mutation? What are its down stream effects in translation?

Mutation in mRNA codon, alters codon to encode different AA than before. No change in length, no down stream effects in AAs

What is the mechanism of Malignant Hyperthermia?

Mutation in the RYR1 gene mutates the Ryanodine receptor making it constitutively open, allowing Ca to influx into the intercellular space, causing continues muscle contraction, hyperthermia, and hyper metabolic symptoms.

Evolutionarily speaking, why is the human genome able to be mutated, causing serious disease?

Mutation is the key to evolution. The Genome must be malleable in order to impart protective and adaptive measures. The unfortunate side effect is that it can be mutated for deleterious effects. Most random rearrangement in the genome is deleterious.

How does CF affect Cholera contraction?

Mutation of CFTR results in protein not making it to the membrane. No CFTR in membrane -> no secretion affect by cholera. CF homozygotes - much less cholera sickness CF heterozygotes - less cholera sickness WT - regular cholera response.

What is the mechanism of Phenylketonuria?

Mutation of the Phenylalanine Hydroxylase (PAH) gene (Or BH4) causes buildup of phenylalanine in blood (PAH degrades Phe) which is toxic to the CNS.

What is the complete molecular mechanism of TSC?

Mutations in EITHER TSC1 or TSC2 Or both -> LOF of the Hamartin/Tuberin -> Decreased tumor suppression and regulation of cell growth/proliferation.

How does Actinomyacin D work to affect DNA replication?

Naturally occurring antibiotic, structural interference. Intercolates into the DNA chain, physically blocks replication machinery.

Where are all of the negative charges concentrated in a cell?

Near the membrane (interior wall). They are more plentiful inside a cell, but they still repel one another, force each other to the walls.

Compare and contrast apoptosis and necrosis in terms of morphology, common triggers of the two phenomena, and relative importance in physiological and pathological processes.

Necrosis - cell death due to sudden injury. - Inflammation due to intercellular contents spilling into extracellular area - Mitochondria swell, then burst. - More pathological than apoptosis Apoptosis - non traumatic cell death - non inflammatory - Nucleus collapses and cell breaks apart into apoptotic bodies. - more physiological than necrosis.

What is the Vm for cells in the body? (neg/pos)

Negative

Why can ant-acids be dangerous for people with stomach ulcers?

Neutralizes acidic environment. Allows for more bacterial survival in gut, increased ulcer progression.

What is the most common WBC in the blood?

Neutrophil

What are the two pathways for DS break repair? When do they occur?

Non Homologous End Joining - Often imperfect, loss of nt - occurs throughout cell cycle Homologous Recombination - perfect repair, swap of DNA between two sister chromatids - Occurrs in S and G2 phase.

Give an example of a sequence specific DNA binding protein regulated by nuclear entry and describe the mechanism by which its entry is controlled.

Nf-kB - Mediates inflammation response. When bound to Ikb is locked in cytoplasm. Ubiquitination of Ikb and subsequent degradation allows Nf-kB to move into nucleus and initiate inflammatory response. Nf-kB target of many anti-inflammatory drugs. OR NF-AT- High intracellular calcium activates calcineurin's phosphatase activity which dephosphorylates cytoplasmic NF-AT. This exposes the nuclear localization sequence, allowing NF-AT to enter the nucleus where it affects transcription of genes involved in the immune response and in heart function. *Note- two commonly used immunosuppresants (cyclosporin and FK506) act by inhibiting calcineurin, thereby inhibiting NF-AT action.

Where on the ribose/deoxyribose sugar does the nitrogenous base attach? the phosphate? The continuing chain of nucleotides?

Nitrogenous base - 1' Phosphate group - 5' Chain - 5' <-> 3' 4' is the only silent, or unused area, just joins to the 5' which is very active.

What causes HPFH?

No δ or β synthesis because of deletions of both genes, coupled with Increased γ-globin expression

What is δβ0-thalassemia?

No δ or β synthesis due to deletion of the coding sequences for both δ- and β-globin.....looks a lot like HPFH, the range of deletion is the only determine factor between the two.

Is the poly AAAAA tail encoded in the original DNA template?

No, the poly A tail is a POST-transcriptional add-on.

Can restriction enzymes cut DNA/RNA hybrids?

No. Cant cut because restriction enzymes only cut dsDNA, but also can not cut due to lack of palindromic sequences (one strand has Thymine, the other Uracil, not palindromic)

Can DNA poly unwind/melt DNA?

No. DNA Helicase does

If a mutation is in an exon, is it guaranteed to alter the final protein product?

No. Exons, or parts of exons, may not be included in the final mRNA product.

Is the conversion from gamma globin predominance to beta-globin predominance instant at or immediately around birth?

No. Gradual process initiating ~ 10 weeks before birth and continuing until 12 weeks after.

Can RNA polymerase locate target genes in DNA on its own?

No. Requires transcription factors and co factors.

Does a heterozygous RB deletion cell express the cancerous phenotype?

No. Though RB is INHERITED in an AD fashion, it expresses as a recessive mutation (if paired with a WT heterozygote, no phenotype)

What is NAHR? Describe its mechanism. How does it contribute to disease?

Non-allelic homologous recombination (NAHR) - When two chromosomes, due to the identical nature of repetitive DNA sequences, recombine at an improper location, within the repeated sequences at different loci. Disease can result.

How does alpha-amanitin function to halt transcription? Which protein does it specifically target?

Non-competitive inhibitor of RNA pol II. It binds the bridge helix in RNA poly II and blocks RNA chain elongation by preventing translocation Alpha-amanitin affects RNA Pol II

What are the primary stabilizers of the double helix of DNA?

Non-covalent bonding Laterally: H-bonding between nitrogenous bases. G <-> C has three (14.1 kcal/mol) A <-> T has two (5.7 kcal/mol) Longitudinally: Stacking of bases. Again, G/C stacked on G/C has stronger bond than A/T stacked on A/T

How does nondisjunction contribute to down syndrome?

Non-disjuction - is the failure of homologous chromosomes or sister chromatids to separate properly during cell division. In trisomy 21 a non disjunction event least to a non-haploid gamete (for chr 21) that later fuses with a haploid gamete to form a trisomy of 21. There are three forms of nondisjunction: failure of a pair of homologous chromosomes to separate in meiosis I, failure of sister chromatids to separate during meiosis II, and failure of sister chromatids to separate during mitosis.

What is Sensory cilia and what is its function?

Non-motile. Appear to function in nearly all sensory pathways (touch, taste, sound..). Believed to be specialized versions of primary cilia.

What disease is associated with GJB2 mutations?

Non-syndromic deafness.

Which tRNA binds to the stop codon?

None. A Protein that whose tertiary structure matches that of tRNA called a Release Factor binds stop codon in A site and.

How much ATP does splicing require?

None. The amount of phosphodiester bonds remains the same in the entire mRNA chain.

Can a CDK unbound to a cyclin still function to regulate the cell cycle?

Nope. CDK = Cyclin DEPENDENT Kinase. Inactive without.

Describe the pathway of the b-adrenergic receptor in the heart

Norepinephrine binds b-adrenergic receptor -> Gs swaps GDP for GTP (Active) -> Moves to Adenyl Cyclase and activates -> cAMP -> PKA -> phosphorylates L-type Ca Channels, opens -> Ca into cell -> Increased rate and contraction of heartbeat.

What are the ranges of CTG repeats in MD for the following classifications? Normal Pre mutation rance Full mutation range (what is penetrance here?)

Normal - 5-34 Pre mutation rance - 34-49 Full mutation range- >50 = 100% penetrance.

What does the retinal reflection look like in a healthy eye? And in an eye with retinoblastoma?

Normal - red RB - White, tumor growth.

What is anchorage independence? How is is used in cancer research/screening?

Normal cells form flat layer on solid support. Require solid surface to grow. Can not grow lose in liquid medium. Cancer cells do not need the 'anchorage' that normal cells do. Can grow in liquid Agar medium. More anchorage-independence - more cancerous transformations that have occurred in a cell.

At what age does a normal baby start walking? A down syndrome baby?

Normal: 1 DS: 2

Transcripts created by which RNA polymerase(s) acquire a 5' 7-MeG cap?

ONLY transcripts created by RNA poly II.

What is alternate segregation? When does it occur? In what does it result?

Occur in a reciprocal translocation heterozygote. The segregation of both normal chromosomes to one pole and both translocated chromosomes to the other pole giving genetically balanced gametes. Occurs in Meiosis 1 Results in a normal phenotype.

Where does DNA methylation occur? What is the target? What is its effects on gene expression?

On cytosines in the DNA chain. These C must be paired with G for methylation to occur. This methylation silences the gene.

Where will the lumenal side of a transmembrane protein in the ER (bound for the outer cell membrane) end up?

On the outside of the cell. Items on the lumenal side of the ER, the golgi, and secretory vesicles are either secreted (secretory protein) or if membrane-bound, sit on the outside of the cell.

What member of the arterial family, when constricted, has the greatest limiting effect on blood reaching the capillaries?

The Arterioles. These are the gatekeepers to the capillary beds and the primary regulator of flow into these areas.

How do gene families and gene duplication facilitate genetic innovation?

One gene can uphold the function of another so that it is allowed to vary. This allowed variance makes room for genetic innovation.

What is TFIIH?

One of the major General Transcription Factors involved the RNA pre-initiation complex. Functions in transcription AND DNA repair.

How many active X chromosomes are there in ISCN: 50, XXXXYY? Explain how this is linked to abnormal presentation

Only one. No matter the number of X chromosome, there is only one active X. The rest are 'turned off' So why is there a disease state if all extra X are inactive? Certain areas on the X chromosomes are NOT turned off in extra copies despite the inactivation of the bulk of the extra X. These extra genes cause abnormalities.

What is an example of a location in the body where transitional epithelia reside?

The Bladder. resilient, stretchable epithelium.

What is a Sense mutation? What are its down stream effects in translation?

Opposite of a nonsense mutation - Changes stop codon to an amino acid. Protein now is much longer than it is supposed to be.

What is an optic glioma?

Optic nerve gliomas are a type of malignant glioma (brain tumor) found in the optic chiasm.

Describe the origin and basic structure of mitochondria

Origin: They are ATP-producing bacterial cells that were phagocytosed (engulfed) by eukaryotic cells long ago so that eukaryotic cells could benefit from their 'power-station' capabilities. Matrix - innermost cavity Inter membrane space - cavity between the two membranes Cristae - projections of inner membrane into the matrix that greatly increase inner surface area of mitochondria.

What are the layers and functions of mucosae?

Outer Epithelium - primary barrier Lamina Propria - CT directly beneath outer epithelium, immune system cells and blood vessels, transport and monitor foreign materials Submucosa - continuous with lamina propria but have more tissues (larger blood vessels, nerves, etc..)

Histologically, describe the appearance of Hyaline cartilage

Outer layer of cartilage, the Perichondrium (P) emitting new chondrocytes (C) into deeper layers that form their own lacunae, or surrounding envelope.

How many different mutations of NF1 have been described in NFT1?

Over 1000

A disufide bond occurs in which conditions? (oxidative/reductive)

Oxidative.

What is the analogous recognition sequence to the Shine-Delgarno called in eukaryotes?

The Kozak Sequence.

Explain how to use Kd to represent binding strength.

P+L = PL (Protein, Ligand) Kd = dissociation constant = [P][L]/[PL] So if the ligand binds MORE to the protein the denominator is larger and the Kd is smaller. MAJOR TAKEAWAY Smaller Kd = Tighter biding Larger Kd = Looser binding If the protein requires LESS ligand to be 50% bound then it must associate tighter to ligands.

In which site (A, P, E) does the initiator tRNA bind?

P-Site.

What are the two mutated proteins associated with PKU? What percentage of PKU cases are associated with each?

PAH - 98% BH4 - 2% BH4 is a cofactor needed for PAH to function.

What is a pheochromocytoma?

PCC - is a neuroendocrine tumor of the medulla of the adrenal glands (originating in the chromaffin cells), that secretes high amounts of norepinephrine and epinephrine. (catecholamines) Norepinephrine release causes trouble sleeping, night sweats...

What is the DNA clamp called in eukaryotes?

PCNA

What is the maternal effect in PKU?

PKU mother (homozygous) has heterozygous fetus (unaffected) but the high Phe in maternal blood damages the CNS of baby, brain damage/congenital malformation.

What is PTC and what does it do?

Peptidyl Transferase Center - The active site on the large subunit. Ribozyme. Site of peptide bond formation.

Perfect and imperfect miRNA matching to target mRNA lead to what?

Perfect = mRNA degradation Imperfect = mRNA degradation or Translational repression.

What is the difference between pericentric and paracentric chromosomal inversions?

Peri - included the centromere Para - excludes the centromere.

What is the perichondrium? What is its function? What does it become in long bone development?

Perichondrium - external layer of fibroblasts and MSCs that generate new chondrocytes Becomes the periosteum in long bone development.

Restriction enzymes recognize which specific sequence in genome?

Palindromic sequences - same in both direction, complimentary.

What are the treatments for Cystic Fibrosis?

Pancreatic Issues. - Enzyme supplementation. - High salt diet. - high calorie, high protein, and high fat diet, and fat soluble vitamin supplements. Lungs - Airway clearance treatment - Antibiotics - Anti-inflammatory

Define paracrine, autocrine, endocrine, and contact-dependent signaling

Paracrine - signal from one cell to other nearby cell Autocrine - cell signals self Paracrine - Cells signals enter bloodstream, signal cells far away. Contact dependent - signal is membrane bound, must make contact with other membrane bound receptor on other cell.

CDK-7 is a kinase. What larger transcription factor is this a part of? What is its phosphorylation target (involved in transcription)?

Part of TFIIH Target is RNA poly. Phosphorylation of the RNA poly triggers it for elongation.

Paternal deletion at the PWS/AS loci cause what? Maternal deletions at the PWS/AS loci cause what?

Paternal deletion - PWS Maternal deletion - AS

What is the clinical criteria for diagnosing TSC?

Patient must have either 2 major features or 1 major feature and 2 minor features.

What is the penetrance of Retinoblastoma? How many cases per live birth?

Penetrance = 90% 1/15000 live births.

What does the term 'penetrance' have to do with pedigrees and the presentation of illness?

Penetration: The fraction of individuals with a trait (disease) genotype who show manifestations of the disease. If all persons carrying a mutation have the trait, the condition is 100% penetrant. If some mutation carriers do not show signs of the trait, penetrance is incomplete (<100%). Someone can have a non-penetrant dominant disorder that you cannot observe. Or inversely a penetrant recessive disorder that is observed (as dominant) in a heterozygous patient.

In regards to irreversible inhibition, how does penicillin work?

Penicillin structurally looks like the normal substrate for an enzyme involved in maintaining bacterial cell walls. Penicillin irreversibly binds the active site of the enzyme, rendering it inactive. Cell walls degrade.

'Peptide' and 'Protein' are referring to AA chains of what lengths?

Peptide - 50 AA or less. Protein - More than 50 AA

Once proper tRNA is located in the A site, does the AA get transferred to the P site or does the Peptide chain in the P site get transferred to the A site?

Peptide chain gets transferred from the P site to the A site.

What is sickle cell trait?

Pertains to heterozygous of HbS/HbA. They are clinically normal except when under severe low pO2 stress.

Describe two major routes for small volume endocytosis.

Phagocytosis - intake of larger solids. Deliver to lysosomes for degradation Pinocytosis - intake of liquids or much smaller volume items, such as ligands to receptors.

What is the phenotypic characteristic of a 46, XY with a deletion of the SRY gene?

Phenotypically normal female.

What is the phenotypic characteristic of a 46, XX with a functioning SRY gene?

Phenotypically normal male

What amino acid buildup is related to PKU?

Phenylalanine (Phe)

What disease is associated with a defect in the PAH gene? What is the inheritance pattern of this disease?

Phenylketonuria Autosomal Recessive

What disease causes a buildup of phenylalanine in the body? Why does it cause this? What can result?

Phenylketonuria (fen-ul-ke-toe-NU-re-uh), also called PKU, is a rare inherited disorder that causes an amino acid called phenylalanine to build up in your body. PKU is caused by a defect in the gene that helps create the enzyme needed to break down phenylalanine. Build up of phenylalanine is toxic to the body causing intellectual disability and other serious health problems.

What early event on the plasma membrane occurs in apoptosis? What does this cause?

Phosphatidylserine, part of the lipid bilayer which is normally only on the inside of the cell, is pushed to the outside of the membrane (by flipase). This is a marker for phagocytitic recognition by macrophages. Apoptotic cell is engulfed and digested. Annexin 5 is a dye that binds phosphatidylserine, marking an apoptotic cell.

What type of bond exists between the mRNA and its 5' Cap? Which carbon of the ribose ring of the 7-MeG cap is associated with this?

Phosphodiester 5' carbon of guanosine cap. So G-Cap on 5' end is normal rNTP added backwards from normal. Not 3' - O - 5', but 5' - O - 5'

What enzyme degrades cAMP into AMP? What would a drug designed to block this enzyme do in regards to BP?

Phosphodiesterase (PDE) PDE blockers -> no cAMP degradation -> inc cAMP -> inc heart rate and force -> BP up.

How does the distal tip of a neuron 'sense' physical feeling?

Physical pressure on the tip of neuron stretches the neuron membrane, opens Na+ channels, Na influx depolarizes cell, signal travels to spinal cord and up to brain. More pressure = more distortion of membrane, more influx of Na, more action potentials -> CNS.

What stimuli are sensed by a signaling cilia?

Physical, light, and chemical.

What is the function of the Gly-rich loop in a PKA?

Physically moves ATP close to protein to be phosphorylated. Must re-open to allow exchange of ADP for ATP which is the rate limiting step.

How do you measure Vm?

Physically pierce the cell with one electrode while leaving the other outside the cell in solution. Measure the potential difference.

Histologically, describe the appearance of plasma cells

Plasma cells are simply lymphocytes that have become active and therefore have a noticeable stained cytoplasmic extension, indicative of protein synthesis and secretory organelle activation. Notice the difference between Plasma cells (P) and Lymphocytes (L) in pic.

Describe characteristic plasma membrane, cytoplasmic, and nuclear events of apoptosis.

Plasma membrane - outward exposure of phosphatidylserine Cytoplasm - Nuclear - shrinks, condenses, can break into multiple nuclei.

Be aware of the different types of cloning vectors and their general features.

Plasmids: Vectors for amplifying DNA sequences in bacteria, max insertion of 20kb into E. coli, simple but inefficient. Bacteriophage: Used to infect E. coli and use its replication machinery to produce the recombinant vector. Insertion up to 25kb, more efficient than plasmid. Cosmids: hybrid of bacteriophage and plasmid: use plasmid replication origin; can take up to 45 kb insert into E. coli. BAC: bacterial artificial chromosome with insert up to 300kb, good for chromosome mapping and sequencing YAC: yeast artificial chromosome with insert up to 2mb, chromosome mapping and sequencing Retroviral vectors: can carry very large inserts; introduce DNA into mammalian cells, delivers gene therapy. (thanks colton)

How are microtubules oriented in the cell? (in regards to their plus and minus ends)

Plus ends toward the outer edge of cell. Minus ends toward centrosome. Initiate growth from gamma tubulin on centrosome surface. Grow outwards.

What viruses create a protease that cleaves eIF-4E?

Polio, HIV, Hepatitis A, Foot-and-mouth disease, rhino virus. These are examples where cellular proteins can continue to be translated in lessened amounts via the IRES pathway.

What are polyuria and polydipsia?

Polyuria - urinating a lot Polydipsia - drinking a lot

Define Population Genetics. What are the 4 main factors that affect allele frequencies?

Population genetics is the quantitative study of the distribution of genetic variation in populations and how the frequencies of genes and genotypes are maintained or change. 1) natural selection 2) genetic drift 3) mutation 4) gene flow.

Describe the procedure, significance and effects of mRNA editing. What gene is an example of this?

Post transcriptional alteration of the mRNA sequence via a separate enzymatic pathway. Intentional changes the resulting protein. ApoB protein Full length protein - liver Truncated protein - intestines. (mRNA edited to include early stop codon)

What are the various functions of non-coding regulatory RNAs ?

Post-transcriptional repression - Translational repression - RNA degradation Transcriptional activation or repression Small RNAs and lncRNAs Epigenetic modifications - Small RNAs and lncRNAs Precursors of small RNAs - miRNAs - piRNAs - siRNAs - Other Modulate alternative splicing Regulation of structural organization - lncRNAs

What is the function of statins and what affect do they have on cholesterol in the cell?

They block the first enzyme (of many) involved in cellular production of cholesterol causing down regulation of cellular cholesterol production.

What are primary and secondary siRNA?

Primary - the siRNA produced via the normal pathway (in pic) Secondary - sirens produced by amplifying (directly reproducing) primary siRNAs.

What is the difference between primary and secondary sex characteristics?

Primary - used in sexual reproduction. (cervix, ovaries, testes...) Secondary - Not used in sexual reproduction (penis, breasts, body shape...) Yes the penis is used, but the differentiation seems to occur on more of a cellular level.

Describe the difference between primary and secondary active transport.

Primary active transporters, like the Na/K pump, derive their energy directly from the splitting/hydrolysis of ATP. Secondary active transport is the mechanism by which most substances are pumped. In this case, the energy to do the direct work of pumping comes not from metabolism (ATP), but from a secondary source. Usually concentrations gradients across membranes.

How does the prion contribute to infectious disease? (mad cow, Kuru...)

Prion confirmation switches to insoluble form (rich in Beta Sheets) and then induces healthy PrP to switch conformation to insoluble form. Proteins then aggregate (due to insolubility) into prion plaques in brain. Misfolded PrP can not be denatured, this is why it can be transmitted via cooked meat/brains.

Where is the primary site(s) of Erythropoiesis: Prior to 5 weeks 5 Weeks to 18 weeks 18 weeks to birth Birth onward

Prior to 5 weeks: Yolk Sac 5 Weeks to 18 weeks: Liver 18 weeks to birth: Liver, Spleen, Marrow Birth onward: Marrow

What two AAs discussed break helices? Why?

Pro and Gly.

What are the two types of karyopherins and their characteristics?

Receptors and Adapters Receptors (e.g. B-karyopherin) - Interacts directly with the cargo protein and the NPC Adapters (e.g. A-karyopherin) - Interacts with the cargo protein and the receptor karyopherin.

What are the clinical manifestations of Duchenne's Muscular dystrophy?

Progressive muscular weakness proximal > distal Calf hypertrophy Dilated cardiomyopathy CK levels 10x normal Onset before the age of 5 Wheelchair bound before 13 Death in their 30's Absence of Dystrophin

What are the clinical manifestations of Huntingtons Disease?

Progressive neuronal degeneration causing motor, cognitive and psychiatric disturbances Age of onset 35-44 Death approximately 15 years after onset

How can one primary transcript result in multiple different proteins in: 1) Prokaryotes 2) Eukaryotes

Prokaryotes - Multiple possbile transcription initiation sites in same mRNA. (Shine-delgarno/AUG pairs, no alternative splicing) Eukaryotes - Alternative splicing (multiple mRNAs from a single primary transcript) - differing start codons used. Same as prokaryotes.

What is the name for the ribosome subunits in prokaryotes? And in eukaryotes? What is the name of the units that they combine to form?

Prokaryotes - 30S and 50S, together = 70S Eukaryotes - 40S and 60S, together = 80S

Why can prokaryotic translation couple to transcription when this same phenomena can not happen in eukaryotes?

Prokaryotes have no nucleus. Transcription and translation machinery are all located together in cytoplasm. Eukaryotes have a nucleus, division of translational and transcriptional machinery.

What bio-molecules make up the ribosome? (alone, not loaded with mRNA) Which biomolecule is performing the catalytic activity in peptide bond formation?

Protein and rRNA The rRNA is the catalytic molecule. Ribosome is a ribozyme.

Explain why sometimes protein disulfide isomerase or protein prolyl isomerases are required for protein folding.

Protein disulfide isomerase - If there are a lot of Cysteines in a protein it often forms a lot of incorrect disulfide bonds. Protein disulfide isomerase reduces improper disulfide bonds and reform them correctly. protein prolyl isomerase - Proline is required in both it trans and cis forms depending on the protein. The conversion between these two forms is too slow. PPI seeds this up.

What secondary structure in PrP changes when the PrP switches to infectious form?

Protein switches from primarily alpha-helices, to primarily beta-sheets.

What is an Aminoacyl tRNA synthetase?

Protein that is responsible of loading each specific tRNA with the correct AA based on the tRNA's corresponding anticodon.

In most diseases the infectious material is DNA or RNA. What is the infectious material in Proin disease?

Protein. PrP

Describe Gel Filtration Chromatography

Proteins separated based on Size. Mixture sent through beads with small divots in them. Small proteins get stuck in divots, large proteins can't stick and pass. Large proteins exit first and small ones last.

Describe Ion Exchange Chromatography

Proteins separated based on charge. Mixture sent through negative beads. + chg binds and stops moving. - chg passes through. After all neg chg proteins out, wash the +chg proteins off beads with solution.

What is an immuneproteosome?

Proteosomes with novel b-subunits that are constructed for a specialized function. Immune system turns on genes to make novel b-subunits in response to pathogen needing specific degradation.

Describe the composition of a microtubule.

Protofilament of MT is heterodimer of alpha and beta tubulin. GTP binding domains of all tubulin subunits facing same way (towards plus end). Protofilaments join together into ring (tube). Freshly added tubulin is GTP bound, older-added tubulin has hydrolyed to GDP. When GTP bound the filament is stable. Not when GDP bound.

What molecule is released in the formation of a phosphodiester bond between two nucleotides?

Pyrophosphate

Hb Kempsey has increased or decreased O2 affinity? What type of hemoglobinopathy is this?

Qualitative Hemoglobinopathy (GOF -> Increased O2 affinity -> No release to tissues -> Disease state.)

Is HbC a qualitative or quantitative hemoglobinopathy?

Qualitative. Alters the conformation of b-globin but does not down-regulate its quantitative amounts. (thats a thalassemia)

What two genes are fused in t(15;17)?

RARa and PML. Retinoic acid receptor-alpha (RARA) gene on chromosome 17 is involved in a reciprocal translocation with the promyelocytic leukemia gene (PML) on chromosome 15, a translocation denoted as t(15;17)(q22;q12). The fusion of PML and RARA results in expression of a hybrid (novel) protein with altered functions. (blocking differentiation)

What is the function of the RB protein?

RB is a regulator of the cell cycle. (Blocks entry into S phase from G1) Inhibitor of cell proliferation. Tumor Suppressor.

What gene is affected in retinoblastoma? Which chromosome is it located on?

RB1 gene Chr 13

What is a Renal Cell Carcinoma? What is meant by clear cell RCC?

RCC - is a kidney cancer that originates in the lining of the proximal convoluted tubule. Responsible for 90-95% of all kidney cancers in adults. Clear cell - most common class of RCC (75%). Clear cell is just referring to the cell's histological appearance of 'clearness' (in pic on the right is ccRCC. High dissolved lipid content in cytoplasm causes clearness.

Northern Blot involves the transfer of what genetic material onto a membrane?

RNA

In most enzymes, protein is the active component. What is the active bio molecule in ribosomes?

RNA - Ribozyme. RNA that has enzymatic activity.

Splicing is energetically catalyzed by which type of bio-molecule?

RNA - the U-snRNAs. (NOT Protein!)

What does RISC stand for?

RNA Induced Silencing Complex.

Which RNA polymerase makes mRNA?

RNA Pol II

What are the 4 RNA polymerases (that we are discussing) in human cells? Where are they located?

RNA Poly I - Nucleus RNA Poly II - Nucleus RNA Poly III - Nucleus Mitochondrial - Mitochondria

What do each of the 4 RNA poly in human cells do?

RNA Poly I - makes rRNA RNA Poly II - makes mRNA RNA Poly III - makes tRNA Mitochondrial - Mitochondrial function (non specified)

In basic terms, describe the Brownian ratchet of RNA export

RNA export facilitating proteins bind RNA, guide through the NPC, are removed one at a time on the cytoplasmic side of the NPC using ATP hydrolysis as RNA is pulled through.

Which RNA polymerase is most numerous in human cells?

RNA poly I - need for ribosomes is extremely large.

Directionality of Transcription: In which direction does RNA poly move along the DNA template strand (which direction does it read)? Which end of the RNA primary transcript emerges first (transcribed first) from the RNA poly?

RNA poly moves from the DNA template's 3' end to the 5' end The 5' end of the primary transcript is transcribed first and proceeds to the 3' which is transcribed last.

What must assemble before transcription can proceed?

RNA pre initiation complex (PIC)

What are SSBs called in Humans?

RPA - Replication protein A.

What is the mechanism of the DNA damage checkpoint that utilizes p53? What does p53 do?

Rad17 binds directly to DNA damage caused by radiation -> Recruits ATM and ATR. ATM/ATR Phosphoylate p53, triggering p53 to activate transcription of p21 which blocks all CDK activity, blocking progression of the cell cycle. Rad17 -> ATM/ATR -> P53 -> p21 -I CDK.

Between nucleus and cytoplasm, where is the RanGDP concentration higher? RanGTP concentration higher?

RanGDP - higher in cytoplasm RanGTP - higher in nucleus

What drug targets m-TOR? What are its effects?

Rapamycin - It prevents m-TOR from being translated. Greatly inhibits translation machinery (eIF-4G), among other things.

What is malignant hyperthermia? Inheritance? What is the mutation?

Rare autosomal dominant genetic disorder that causes hypermetabolic/hyperthermic/skeletal muscle damage when under general anesthesia. 70% mortality if not treated. Mutation in the RYR1 gene.

What is the difference between fast twitch and slow twitch muscle?

Rate of myosin turnover is faster in fast twitch Fast Twitch - 20 times per sec Slow Twitch - 5 times per sec

If the Rb gene is homozygously deleted in many cells in the body (inherited) Why are tumors only localized to the eye?

Rb homologues p107 and p130 are not expressed in retinal cells. Rb knockout results in loss of cell cycle control. Other cells in body express p107/p130, knockout of Rb in these cells results in no phenotype.

What is the equation for the equilibrium constant of a chemical reaction?

Reaction: A + B <-> C + D Eq Constant = Keq Keq = [C][D] / [A][B]

What is a common cellular metabolism by product that can damage DNA? What type of damage do they cause?

Reactive Oxygen Species (ROS) Oxidative damage - (shown) can block replication and transcription.

What is BRCA1? What proteins activate it? What does it do?

Regulator in many DNA repair pathways. Activated by ATM and ATR kinases (phosphorylation) That is why mutations in BRCA1 are cancer associated, lack of DNA repair.

What is meant by metacentric, submetacentric, and Acrocentric chromosomes?

Relation of location of centromere between the p and q arms

What is the effect of Nitric Oxide on muscle? Which muscle type does it affect?

Relaxes smooth muscle.

How does phosphorylation relate to the drug Gleevec? What is the mechanism here?

Remember: a kinase is a protein enzyme that phosphorylates targets. In center cells, the brc-abl kinase is always phosphorylating its substrates (on ser, thr, and tyr residues) which leads to uncontrolled cell proliferation. Gleevec is designed to bind to the kinase active site of bcr-abl which blocks its phosphorylating activity, and thereby blocks uncontrolled cell proliferation.

Where on DNA strand does replication start? In which direction does DNA synthesis proceed?

Replication Origin Replication proceeds in both directions of double strand simultaneously. The machinery moves along the template in the 3' -> 5' direction and produces the DNA replicate in the 5' -> 3' direction.

What is heterochromatin?

Repressed DNA. DNA less accessible. Is hypoacetylated.

Where does epigenetic reprogramming occur? And Methylation Maintenance?

Reprogramming - Gametogenesis, germ cells Maintenance - Somatic cells.

What is a SINE? What percentage of the human genome do they occupy?

SINE - Short Interspersed Nuclear Elements are retrotransposons that have accumulated to very high copy numbers in many mammalian genomes. 13% of the human genome

How do proteases and peptidases work? Where and how do they cleave?

They cleave peptide bonds between specific AA residues in a peptide chain via hydrolysis.

What mutated gene and protein are associated with each of the following diseases Retinoblastoma NFT1 Tuberous Sclerosis Osteogenesis Imperfecta

Retinoblastoma - Gene/Protein: RB1 NFT1 - Gene: NF1, Protein: Neurofibromin Tuberous Sclerosis - - Gene: TSC1, Protein: Hamartin - Gene: TSC2, Protein: Tuberin Osteogenesis Imperfecta - Gene/Protein: COL1A1

What is a retrotransposon?

Retrotransposons are genetic (DNA) elements that can amplify themselves in a genome (using an RNA intermediate, note the 'retro-' part of the name) and are ubiquitous components of the DNA of many eukaryotic organisms.

Where does reverse transcriptase originally come from?

Retrovirus'

What are three types of Direct Reversal repair of damaged bases?

Reversals: Reverse damage 1) ssDNA backbone break -> DNA Ligase 2) Thymine Dimers -> Photolyase 3) Base Akylation -> MGMT MGMT - methylguanine methyltransferase.

How is an RNA/DNA hybrid formed? (one strand of each complimentary)

Reverse Transcriptase activity - binds RNA on 3' end moves 3' -> 5' and creates complimentary strand of DNA called cDNA.

Describe the most fundamental conclusion drawn from the Ribonuclease refolding experiment. What protein was used for this experiment?

Ribonuclease A 1. All the information needed to fold the protein correctly is embedded in the primary sequence. 2. The environment provided by the inside of the cell is not always required.

How does cDNA relate to SINES and LINES

SINES and LINES can encode an RNA that is retro transcribed into cDNA and inserted back into the genome. So SINES and LINES, sitting in the genome may be composed of cDNA as opposed to DNA poly-replicated DNA.

In what conformation are most alpha-helices in the human body?

Right handed. Think DNA.

What causes the anemia witnessed in both Sickle cell and HbC diseases?

Rigidity of the cells causes them to break apart earlier than normal. Reduce overall count of RBC.

What are two disease where histone acetylation is altered? What is the mechanism of each?

Rubinstein-Taybi Syndrome- A rare genetic multi system disorder. Results from mutations in one copy of the CREB binding protein (CBP) gene. CBP is a histone acetyltransferase. Leukemia- A hematopoietic malignancy. Fuses HATs or HDACs, altering their activity

What is the basic common process common to southern, northern, and western blotting?

Running on gel, transfer to membrane, expose membrane to probe. Probes: - DNA - sense or antisense to target area - RNA - antisense to mRNA - Protein - antibody

In what cell phase is all DNA duplicated?

S Phase.

What are the two alleles for the mutated ATD gene? What is the genotype for a person that has 0-15% activity of Alpha 1 Antitrypsin?

S and Z Z/Z = 0-15% activity (S/S ~ 50%-60%)

The entry into what cell cycle phases can be inhibited by the DNA damage checkpoint system?

S, G2, and M.

What are the differences and similarities between siRNA and miRNA?

SAME: all steps after procuring and processing the double stranded source RNA. DIFFERENT: Source dsRNA - siRNA - longer viral or endogenous dsRNA, two SEPARATE RNA strands in ds formaiton - miRNA - endogenous RNA forming hairpin, SAME RNA in hairpin. Processing of dsRNA - siRNA - Dicer cuts dsRNA in middle, sizes to 22t - miRNA - Dicer cuts off only hairpin turn, sizes to 21t Target - miRNA - all mRNA - siRNA - Mostly Viral mRNA

Describe how proteins can be separated by gel electrophoresis and displaced on a SDS polyacrylamide gel

SDS coated proteins migrate through the gel based on size. Larger = slower.

WTF is SDS? What does it do to proteins?

SDS denatures proteins and coats them in negative charge. That way in electrophoresis the protein ALWAYS moves towards the positive end of the gel contraption.

What population is more at risk for the HbE mutation? What can its penetrance be in these populations?

SE Asia. Nearly 100% penetrance in some areas of SE Asia

What population has the highest carrier rate for HbE? What percentage of the population?

SE Asian 7%

What population has the highest carrier rate for B-thalassemia? What percentage of the population?

SE Asian and Mediterranean 4-5%

The populations below are at a higher risk for which diseases/mutations (discussed in unit 2) SE Asian African N. European Ashkenazi Jews

SE Asian: - a-thal 1 allele (--) - HbE - B-thalassemia African - HbS - a-thal 2 allele (a-) N. European - PKU - ATD - Cystic Fibrosis Ashkenazi Jews - Gauchers - Tay-Sachs

Which population is at higher risk for HbH disease?

SE asia. HbH = (a-/--) a-thal 2 groups not at as high a risk (a-/a-)

What protein domains recognize and bind the intercellular RTK domain? How does this confer signaling specificity?

SH2 domains. Different SH2 domains recognize different phosphorylated-tyrosines. The differing SH2 domains are bound to differing adapter proteins leading to different signals coming from the same RTK.

What are the differences and similarities between Duchenne's and Beckers Muscular dystrophy?

SIMILAR Both are mutations to the DMD gene. Both cause decreased lifespan Dialated Cardiomyopathy DIFFERENT Mutation in Duchennes = frameshift, no DMD Mutation in Beckers = No frame alteration, diminished DMD Onset: Later in Beckers, early in Duchennes (before 5yo)

How does salt concentration affect DNA melting point?

Salts interact with and stabilize neg Chgd DNA backbone. Loss of salts means neg backbones exposed and interact, pushing apart. Less salt = Lower Tm. Higher Salt = Higher Tm.

How are siRNA formed in exogenous and endogenous cases?

Same formation - different source dsRNA Exogenous - viral introduced dsRNA Endogenous - Formed in Cell Dicer cuts dsRNA sizes to 22nt. Argonaut binds, selects one strand. This forms siRISC which binds and cleaves target mRNA. (Same as miRNA)

What do mutations in HEXB cause?

Sandhoff Disease. Similar to TS

Define the role of "satellite cells" in skeletal muscle development and repair.

Satellite cells - stem cells that are source for new myoblasts to repair injured muscle. These cells are thought to be damaged in Duchenne's Muscular Dystrophy.

What cells create the myelin sheath?

Schwann cells.

What is a genetic linkage study?

Searching multiplex families for 'linked' segments inherited with disease phenotype.

Describe the function of second messengers in receptor signaling and give two examples for how they are generated by activated G proteins.

Second messengers carry out and amplify signals from receptor transmembrane proteins/mechanisms. 1) cAMP generated by AC 2) IP3 generated by cleavage of PIP2 by PLC

Compare and contrast the secondary and tertiary structures of keratin and collagen

Secondary - Helices - Keratin - right handed - Collagen - left handed Tertiary - Subunits of coiled-coil - Keratin - 2 helices - Collgen - 3 helices

What type of transporter moves AA and Glucose into cells from gut lumen?

Secondary active transport - uses the movement of Na+ across membrane to fuel transport of AA and glucose.

List other "tools" of signaling pathways, including at least three 2nd messengers.

Secondary messenger examples: Ca cAMP gAMP NO IP3 DAG

Identify pitfalls of the medical culture in dealing with patients with Turner Syndrome. (what do we as MDs do incorrectly)

Secret Keeping - not directly honest with patient. not full disclosure of syndrome. Difficulty in communicating infertility Perceived negative experience with MD

What are the two main components of exocrine glands? what are their basic functions?

Secretory Units and Ducts. Secretory units - clumps of secretory epithelial cells Ducts - tubular structures that emanate from the secretory units

How do introduced siRNA get into target cells?

See pic

Identify the parts of a phospholipid, sphingolipid, and cholesterol.

See pic - All are amphipathic Phospho - long hydrophobic carbon chains, with trans dbl C bond Sphingo - saturated carbon chain with Nitrogen in chain. Cholesterol - hydrophobic carbon chain attached to 4 hydrophobic carbon rings (OH infers hydro-philicity and is the only part that associates with extracellular environment)

What is the process by which a cell deals with an amount of errors or mutations in DNA replication that the normal repair pathways can not keep up with?

Translesion Synthesis

Which AA can be phosphorylated? Why?

Ser, Thr, and Tyr AA can be phosphorylated. They contain functionally accessible -OH residues to which phosphate can be added.

What AA are commonly reversibly phosphorylated?

Serine Threonine Tyrosine

Which GI disease is associated with hematochezia?

Ulcerative Colitis

What is the Shine Delgarno sequence? How does it function? What Specifically does it bind to? Where is it located?

Shine-Delgarno sequence - ribosomal recognition site in the prokaryotic mRNA. The 30S subunit of the prokaryotic ribosome has an anti-shine delgarno, recognizes Shine delgarno and base pairs (bind). This properly localizes the mRNA for translation. Shine Delgarno is located just upstream of the AUG codon. This is how the Shine Delgarno properly locates the start codon in the ribosome.

What is HbS?

Sickle Hemoglobin - tetramer, alpha and (mutated) beta globin.

What cleaves the signal sequence off of an ER bound mRNA? Where is it located?

Signal peptidase inside the ER.

How can polymorphism be used to trace evolutionary backgrounds?

Similarity/differences in AA sequences between polymorphic proteins denotes degree of relation and possible branch points in lineage tree. More similar = more related Less similar = less related.

What is simple b-thalassemia? Complex b-thalassemia?

Simple β-thalassemia: mutations or deletions affect β-globin chain alone. Other genes in the β-globin cluster unaffected. Complex thalassemia: Large deletions that remove the β-globin gene plus other genes in the β-cluster, or the LCR.

What percentage of the post-duodenal GI cells are in the small intestine? And in the large? Relate this to cancer incidence in each area.

Small - 90% Large - 10% SI cells reality undergo apoptosis. LI resist. LI cells exposed to more toxic materials, this is why it must be resistant to apoptosis, but resistance to apoptosis increases risk for cancerous growth.

What is an SNP?

Single Nucleotide Polymorphism - DNA sequence variation occurring commonly within a population in which a single nucleotide — A, T, C or G — in the genome differs between members of a biological species or paired chromosomes. For example, two sequenced DNA fragments from different individuals, AAGCCTA to AAGCTTA, contain a difference in a single nucleotide. In this case we say that there are two alleles.

What prevents ssDNA from annealing to itself in DNA replication in prokaryotes?

Single Stranded Binding Proteins. (SSB)

What is the source for piRNA? What is their primary job.

Single stranded RNA. Control mobile elements (transposons)

Which disorders/diseases often present with characteristic and recognizable patterns in pedigrees?

Single-gene disorders (also called Mendelian disorders). Disorders due to the mutation of a SINGLE gene.

Upon which factor is gel electrophoresis dividing DNA?

Size. Larger molecules (strands of DNA) move slower and smaller move faster.

What are the defining characteristics of each muscle cell: Skeletal Cardiac Smooth

Skeletal - striated due to repeating sarcomeres, multi nucleated, nuclei towards periphery of cell, largest diameter of muscle cells. Fast tension development. Cardiac - Striated, single nucleated, intercalated discs = adjacent cells tied together and gap junctions for AP transmission (synchronous contraction), mid sized in diameter. Fast tension development. Smooth - NOT striated (smooth), single/central nuclei, smallest in diameter, differing mechanism of contraction than skeletal and cardiac. Also, some have gap junctions. Slow tension development.

What are the three functions (we discussed) for myosin?

Skeletal muscle contraction, cytokinesis, and intercellular transport (Myosin V).

What are the clinical findings on the skin for TSC?

Skin Findings 1) Hypopigmented Patches 2) Angiofibroma - skin bumps, non fluid-filled 3) Shagreen Patch - Areas of thick leathery skin that are dimpled like an orange peel 4) Ungual fibroma - are smooth, firm, flesh-coloured growths adjacent to, or arising from underneath, the nails.

What sleep disorder is commonly present within patients with down syndrome? Why?

Sleep Apnea - mid facial hypoplasia results in blocked or restricted areas in ENT.

How does a DNA-dependent ATPase function to alter chromatin conformation?

Slide DNA along histone octamer. Expose new DNA area.

Marathon runners have more of which type of muscle fiber?

Slow

What protein activates the formation of actin polymers (via the formin pathway (what activates formin))?

Small GTPases. GTP hydrolyzing protein activates formin which allows actin to polymerize.

Histology: What is meant by the 'fixation' of tissues?

Soak tissue in a solution that induces cross-linking between proteins which fixes macromolecules in their native state and location. Ex: Formaldehyde.

Describe how certain therapies might improve nerve function.

Sodium and Potassium channel blockers. Block the increased release of K and Na in demyelinated areas of axon. This improves axon conduction. Also, medications that decrease the permeability of the blood-brain barrier. No entry of immune cells into CNS space.

Describe the three main stages that are repeated during PCR amplification. State the approximate temperature of each step, and relate this temperature to the state of the DNA molecules in the PCR reaction.

Solution of dNTPs, DNA Poly, Oligo Primers, 1) Denature DNA, high temp - 95 deg C 2) Cool and allow primers to anneal - 55 DegC 3) Warm for elongation by DNA poly - 72 Deg C

Describe three characteristics of a hybridization probe that you will use to detect a specific DNA sequence on a membrane.

Specific length - alters the Tm Specific sequence- so it can bind to the DNA you're interested in. Visualizer - Radio-labeled or some other visualization characteristic Quantity - add it in sufficient quantities to outcompete the other strand of DNA in annealing to its target DNA.

How is specificity achieved in regulation of gene expression?

Specificity depends on binding of transcriptional activators/repressors (factors) to DNA control elements. Combinatorial control - various combinations of thousands of transcription factors available.

What method of genetic screening would you want to use to filter out x-linked diseases?

Sperm Sorting.

What is one example of a disease caused by a splicing defect?

Spinal muscular atrophy.

What is the name for the complete assembled complex involved in nuclear splicing of mRNA? What is it composed of?

Spliceosome. The 5 U snRNAs and various protein complexes.

Describe the process of a Western Blot. How is it used in HIV diagnosis?

Starts with gel electrophoreisis (separates proteins on size), then gel is blotted agains a membrane, transferring all proteins in gel, then gel is washed with a specific antibody (invisible, specific to protein of interest) then the gel is washed with another antibody that binds ALL antibodies. Color shows on membrane. When used in HIV, Just do the above with the patients blood then wash the membrane with an antibody specific to HIV.

What happens to mice with a knockout in ATG7?

Starved to death right after birth. ATG7 essential in autophagy pathway.

Describe the two steps of splicing involving the branch point A and the joining of the two ends of adjacent exons. What is the conformation of the released intron?

Step 1: Attack by the 2' OH of the branch point A to the phosphodiester bond between the 3'OH and the 5' phosphate of the preceding intron/exon junction. (takes phosphate leaves 3' OH on exon) Step 2. Attack by the 3' OH of exon 1 to the phosphodiester bond between the proceeding intron/exon. (removes intron entirely) Intron released as a lariat. (all components of intron now removed - the 5'GU, the 3'AG and the branch point A)

What is hydrops fetalis?

Stillborn.

In regards to threats to normal Mendelian inheritance patterns, what is a Stochastic effect?

Stochastic (random) effects can influence the expression of phenotypes. This concept pays homage to the fact that some phenotypes may be influenced by chance events/processes absent any obvious genetic/environmental factor. In other words: GOK (God only knows)

What is the signal in a TMD1 that tells the translocon to place the protein into the membrane?

Stop Transfer

What role to globular proteins serve in the body?

Storage of ions and molecules - myoglobin, ferritin Transport of ions and molecules - hemoglobin, serotonin transporter Defense against pathogens - antibodies, cytokines Muscle contraction - actin, myosin Biological catalysis - chymotrypsin, lysozyme

True or False Cardiac and Smooth muscle can contract without signal from a neuron

TRUE Cardiac and smooth muscle on the other hand are innervated but can function without nervous innervation. They have an innate excitability that is modulated by excitatory and inhibitory innervation.

What are the two reasons that most published genetic associations are false-positives?

Stratification - there is no such thing as a pure population against which you can ethnically control. Bias to publish positive results - we are biased towards positive results. No publication of null, or negative results.

How does Doxorubicin affect DNA replication?

Structural interference. Intercolates into the DNA chain, physically blocks replication machinery.

What is an axoneme and what is its function?

Structural skeleton of the cilium.

Fibrous proteins typically serve what role in the body?

Structural.

How does Actinomycin D function?

Structurally. Intercolation into the DNA chain. Blocks RNA polymerase, transcription blocker. Very toxic.

HPFH individuals are clinically normal but have increased HbF amounts. How does this affect pregnancy where the oxygen exchange between fetus and mother is based on the differing O2 affinity between HbA and HbF?

Studies show: When HbF > 70% of all Hb then growth-restricted babies result. HPFH ~ (17%-35%) so unsure if is concern. HbF testing in HPFH mothers recommended.

What neurological disorders are associated with TSC

Subependymal growths Seizures Autism Cognitive Impairment ADHD Behavioral and emotional problems.

What are the sympathetic and parasympathetic agonists for GPCR that we discussed? What kind of GPCR binds each?

Sympathetic - Norepinephrine, Epinephrine. - Adrenergic receptors bind Parasympathetic - Acetylcholine - Muscarinic receptors bind

What are the two states of Hemoglobin, what causes these changes, and which has higher affinity for O2 binding?

T = Tense State - caused by lack of O2 binding to Hemoglobin protein body. LESS affinity for O2. R = Relaxed state - caused by binding of O2 to Hemoglobin protein body. INCREASES affinity for O2. Relaxed when it has O2, tense when it doesn't, kinda like us.

What are Th1 and Th2 cells? How do they affect inflammation?

T-helper cells, arisen from T-cells. Th1 - pro-inflamatory response system Th2 - Anti-inflammatory response system.

What is TBP? What does it do?

TATA binding protein - general transcription factor. Binds to the TATA Box (repeat of TATAA ~30bp). Signals binding site for RNA pol I, II, and III.

Which transcription factor remains bound to the DNA once elongation has initiated?

TBP

What general transcription factor is necessary for transcription by RNA pol I, II, and III?

TBP - TATA binding protein.

What variation of the TFII protein contains the TBD?

TFIID

Which of the TFII proteins contains a TATA binding protein component?

TFIID

True of False If infected with Cholera you will almost certainly live if you hydrate

TRUE

True or False AR itself is a DNA binding transcription factor.

TRUE

True or False Autosomal dominant diseases frequently have late onset

TRUE

True or False High income countries have the highest rate of MS

TRUE

True or False Ion channels are always passive, in that they always allow ions to move down electrochemical gradient without active intervention

TRUE

True or False Many cells in the body are impermeable to Na but the apical side of epithelial cells is permeable to Na

TRUE

True or False Only cardiac and skeletal muscles have Sarcoplasmic reticulum and the T-Tubule network

TRUE

True or False Ossification in long bone initiates at the diaphysis and THEN occurs in the epiphysis

TRUE

True or False Some patients infected with Cholera are completely asymptomatic

TRUE

True or False The epidermis is an epithelium

TRUE

True or False Trinucleotide expansion is more likely to occur in gametogenesis

TRUE

True or False Cardiac and Smooth muscle cells BOTH have only one nucleus.

TRUE

True or False Endocrine cells release their secretions from their basolateral membrane

TRUE

True or False Epithelia line just about all the tissues of the human body that face the outside world

TRUE

True or False Fragile X is the most common cause of inherited developmental Delay

TRUE

True or False Increasing a membrane's permeability to a certain ion moves the Vm towards that Ions Equilibrium potential value

TRUE

True or False Stem cell regulation is regulated by ligand secretion by cells in its local environment as well as endocrine signaling from far away tissues

TRUE

True or False Temperature sensing axons are among the smallest and therefore conduct signal the slowest.

TRUE

True or False Adult Hemoglobin (HbA) is a tetra dimer

TRUE 2 alpha globin and 2 beta globin chains.

True or False The Na/K pump uses ATP

TRUE About 1/4 to a 1/3 of all energy used at rest is used to pump ions.

True or False Skeletal muscle cells have multiple nuclei per cell

TRUE Actually hundreds of nuclei per cell.

True or False Smaller axon fibers (<1micron) have faster CV if they are not myelinated

TRUE Axons smaller than 1 micron in diameter conduct faster if un-myelinated Axons bigger than 1 micron in diameter conduct faster if myelinated.

True or False A balanced RT results in a DECREASED number of chromosomes.

TRUE Balanced fusion of two acrocentric chromosomes results in one less chromosome with no loss of euchromatic material. UNBALANCED RT = same number of chromosomes.

How does tamoxifen act in breast cancer therapy? What is its mechanism?

Tamoxifen inhibits estrogen receptor by preferentially binding to ER -> estrogen can not bind -> no recruitment of co-factors, no activation of transcription. ER-Tamoxifen complex can also act to recruit repressors to block transcription. Why does this even do anything cancer related? - Some cancer cells require estrogen and its effects in order to grow. Effects blocked, growth blocked.

What is the physical characteristic of thalassemia major RBCs, observed in a blood smear?

Target Appearance. Target Cell. Most RBC = Target cell in thalassemia major. Normal RBC = central pallor (paler in middle)

How do Etoposide and Camptothecin work to affect DNA replication?

Target topoisomerases that relax DNA supercoiling. Drugs that interfere with this process usually leave DNA breaks that cannot be repaired.

Why are HELA cells immortal?

Telomerase is constitutively active.

Regarding a histone, which is an octamer of protein subunits, when we discuss the structure of a single subunit we are discussing its _____________ structure, and when we discuss the octamer structure we are discussing its ____________ structure. Think: Primary, secondary....

Tertiary - subunit Quaternary - assembly of subunits.

Explain the role of loops in protein structure and function.

Tertiary structure importance.

What hormone is needed to signal mesonephric ducts to differentiate into their final sexual form?

Testosterone.

What are the androgens in the human body? What is the most common androgen?

Testosterone. Dihydrotestosterone (DHT) and Androstenedione Testosterone is most common

What is a disease that can arise from a mutated DNA control element?

Thalassemia - an anemia, deficient production of beta globin due to lack of transcription factor binding (mutated binding site) Hemophilia B Leyden - Is an X-linked disorder that affects clotting. Affected males have 1% of normal factor IX. Fragile X-Syndrome - retardation. Increased transcriptional silencing of the FMR1 (synapse involved) gene.

What is a disease example of a phenocopy?

Thalidomide - pregnant women once took thalidomide for nausea -> caused limb malformation in offspring which was not genetic in nature, but mimicked genetic limb malformation.

What is meant when saying that transcription is completely 'processive'?

That the SAME transcription machinery that starts the transcription process completes it. No switching or rearranging of transcription machinery components along the way. No multiple locations to start transcription simultaneously. Approx 2000 bases per minute. Continuous process. This is why some genes take many hours to translate and therefore must have many gene locations in the genome (Ex: The gene for rRNA is in many locations in the human genome. Very large need for this)

What is Chargaff's rule?

That the concentrations of: Purines (G+A) = Pyrimidines (T+C) AND G = C A = T

What determines the 'strength' of a particular Start codon (AUG) in eukaryotes?

The 'strength' of the AUG's partner Kozak sequence. Strength of partner Kozak is determined by how closely the Kozak sequence mimics the consensus Kozak sequence. (most common, strongest sequence)

To which end of the tRNA does the AA attach?

The 3' end.

Which end (3', 5') of the customized primer in allele-specific PCR is assaying the mutation?

The 3' end. That way if there is a mismatch, a normal DNA poly elongation at the 3' can not occur due to mismatch.

What physical aspect of the enzyme affects the rate of a reaction? How does this relate to the transition state and the rate of a reaction?

The 3D conformation of the active site of an enzyme is tailored to bind the transition state conformation of a reaction, stabilizing it, and thereby lowering the amount of energy required to reach the transition state. The substrate is INDUCED to adopt the transition state.

What is the 'wobble position' in codons? Where is it located in the codon? In the anticodon?

The 3rd nucleotide position in the codon and the 1st in the anticodon (read from 5' -> 3'). Wobble refers to the leniency in regards to the specific nucleotide pairing in the codon/anticodon relationship. In other words: in the wobble position, G can pair with U....

What region of the RNA sits between the 5' cap and the start site for translation?

The 5' Untranslated region.

Describe the epigenetic phenomena in mice that leads to the difference in coat color and body size.

The AGOUTI gene when methylated confers a 'normal' phenotype. If mice are fed a diet that limits their cellular ability to methylate (no precursors) then AGOUTI is left on.

Why has the Ashkenazi Jew (AJ) population been important for screening for TS?

The AJ population contains 3 mutant alleles associated with TS that account for 95% of all mutated alleles associated with TS. These alleles are used in all testing.

Describe the genetic basis and mechanism for Angleman Syndrome

The AS region of chromosome 15 has 2 Unique, maternal-only expressed genes. Therefore if you: 1) Lack the maternal homologue (deletion) 2) Have disomy of paternal homologue and no maternal homologue or 3) Mutation of imprinting center. you will lack maternal-specific genes from ch15 and develop AS.

What 2 features (of the 4 discussed) are distorted in inactive PKA?

The Activation loop and The ATP binding pocket

When do centrioles duplicate?

The G1 to S transition

What is the primary cause of gastric ulcers?

The Helicobacter Pylori - bacteria that can survive low pH of gastric juice.

What signal on a protein tells COP1 to take it back to the ER?

The KDEL sequence, 4 amino acid sequence (lysine-aspartate-glutamate-lucine).

Where in the body is the most waste (in moles) released from the body?

The Lungs - 14.5 moles of CO2 a day.

What are N-telo peptides? What are they used for?

The N termini that have been cleaved off of the extracellular collagen bundle. Can be used to diagnose connective tissue disease. Measured in blood circulation.

What happens at the initiation of REpolarizaiton?

The Na+ channels all stop being permeable. K+ channels open.

Shine Delgarno binding places the start codon in which site in the ribosome?

The P Site.

Describe the genetic basis and mechanism for Prader-Willi Syndrome

The PWS region of chromosome 15 has 5 Unique, paternal-only expressed genes. In mother these genes are methylated/silenced. Therefore if you: 1) Lack the paternal homologue (deletion) 2) Have disomy of maternal homologue and no paternal homologue or 3) Mutation of imprinting center. you will lack paternal-specific genes from ch15 and develop PWS.

What does the neg/pos result of a Gibbs free energy indicate?

The Thermodynamic Favorability of a reaction. Negative = favorable, will happen spontaneously at constant temp Positive = unfavorable, will NOT happen spontaneously at constant temp.

Describe x-inactivation. Process, molecular mechanism....

The X chromosome to be inactivated transcribes XIST RNA which wraps the chromosome and recruits DNA methylators and histone deacetylases. 'Silences' most (85%) of the chromosome.

What are the proteins in the g-protein heater-trimer?

The alpha, beta and gamma subunits. BUT beta and gamma are so tightly associated that they are commonly drawn as one.

What is HbA2?

The alpha2 delta2 tetramer composing ~ 3.5% of adult Hemoglobin.

Between which two AA branches does a peptide bond form?

The amino group of one AA to the carboxyl group of the next.

From where can you gain cellular samples for testing of trisomy 21 for an unborn fetus?

The amniotic fluid or the chorionic villus

What determines the rate of a reaction?

The amount of activation energy needed for reaction to occurr. This does NOT mean that very favorable reactions (large -∆G) will go faster. All that matters is the activation energy in regards to rate.

What are the characteristics of large vessels and the aorta?

The aorta and larger arteries branching from it are referred to as elastic arteries. Has intima, myointimal cells, 30-40 layers of elastic membrane, smooth muscle sandwiched in, and vaso vasorum

What is a sarcomere?

The area of a muscle fiber from one z-disc to the next z-disc. Contains the myosin and actin filaments involved in contraction.

Where is collagen 4 located?

The basement membrane (basal membrane)

What is a reciprocal translocation?

The breakage and rejoining of 2 non-homologous chromosomes, with a reciprocal exchange of the broken segments.

What is a Robertsonian translocation (RT)?

The joining of two acrostic chromosomes at the centromere (or the short arm.)

What is a transit amplifying cell?

The daughter cell of a stem cell that also proliferates itself but at a much faster rate than stem cells. Similar to stem cells but they produce only differentiated cells either directly or via the amplification pathway. See pic.

What is expressivity and how does it affect the observation of normal Mendelian inheritance patterns?

The degree to which a trait is expressed in an individual. Expressivity is analogous to a light dimmer (the light is 'on' but the brightness (expressivity) exists along a spectrum (of severity)). The variation in phenotype is explained (in part) by sex influence, environmental factors, stochastic effects, and modifier genes.

Define 'primary transcript'

The direct product of transcription. Not processed into mature RNA yet.

Where does the energy come from to catalyze peptide bond formation?

The energy for peptide bond formation comes from the ATP used in tRNA charging

What is the second law of thermodynamics?

The entropy of the universe is always increasing. (There will always be an increase in disorder)

What is meant when an enzyme increases 'effective concentration'?

The enzyme's effect is to line up two substrates to increase their reaction probability with one another.

One way to think of insulin

The key that opens the lock for glucose to enter cells/tissues for use/storage Stores Energy!

What is the first relapse in MS?

The first clinical sign. The first de-myelinating of an area of the CNS that causes externally visible symptoms. Patient can accrue 5-10 lesions well before the first symptoms.

What is the end replication problem?

The gap on the end of the lagging strand, left because the DNA poly could not proceed to the end.

What is the function of integrins in cell motility and cell survival?

They bind ECM components (about which they are specific) and grip for cell movement. Integrins also signal the cell to tell it that it is adhered, which blocks apoptotic pathways. Nearly all human cells need to be adhered to survive.

What is the ground substance?

The hydrated aqueous gelatinous material in which the structural fibers of the extracellular matrix are enmeshed

What post-translational AA modification is related to Scurvy? What does this cause? How?

The hydroxylation of Proline into Hydroxyproline. Hydroxyproline is rich in health collagen. The enzyme that adds the OH onto the proline requires vitamin C. When vit C is deficient, no hydroxyproline and weakened collagen overall.

What hemoglobin tetramer is present from ~ week 5 -> birth in a severe b-thalassemia patient?

The normal tetramer. HbF = a2g2 Alpha 2, gamma 2. Remember, no beta globin in tetramer that early.

By the way, what is cytogenetics?

The observation and analysis of chromosomes in individual, mitotic cells.

Of the two centrioles, which one is used for the basal body of a cilia?

The older one (the centriole that was the mother in the last duplication)

What is PMCA?

The plasma membrane Ca2+ ATPase (PMCA) is a transport protein in the plasma membrane of cells and functions to remove calcium (Ca2+) from the cell. Uses ATP.

Which end of an MT resides at the distal end of a cilia?

The plus end.

Which end of Actin is the growing end?

The plus end. This is the ATP bound end.

What is genetic linkage?

The principle that genes/alleles that are physically close to each other on a chromosome tend to not get separated in meiosis and recombination. They are typically inherited together.

Which has more osmolarity a 2M solution of CaCl2 or a 3M solution of NaCl?

They are the same. 2M of a 3 particle molecule = 6 osM 3M of a 2 particle molecule = 6 osM

What are the p, q, and centromere regions on a chromosome? How do they compare?

The q is the longer arm and the p is the shorter arm of the chromosome. Centromere is the region where they join.

What is kcat?

The rate constant of the rate limiting step of a reaction. The rate of the 'choke point' of a reaction sequence is equal to the rate of the reaction overall. kcat is the "turnover number" for an enzyme. It measures the number of substrate molecules turned over (into product) per enzyme molecule, per second.

What is allosteric regulation?

The regulator binds at a site other than the active site and alters the confirmation of the active site (in activators, it alters the active site to make it more favorable for substrate binding)

What does Vm depend on?

The relative permeability of a membrane to certain ions.

What is the Philadelphia Chromosome?

The resulting chromosome of the t(9;22) CML related fusion.

What aspects of cardiac and skeletal muscle allow for uniform and simultaneous contraction?

The sarcoplasmic reticulum and the T-Tubule network. AP penetrates and Ca++ release occurs in all areas surrounding all myofibrils.

Define 'transcription unit' How does this relate to a 'gene'?

The segment of DNA which gets transcribed into RNA. A gene comprises a transcription unit plus flanking non-transcribed "regulatory" DNA sequences.

What is exome/genome sequencing? How does it differ from GWAS?

The sequencing of only the protein encoding areas of the genome (~1%). GWAS sequences the entire genome.

What is a Holliday junction?

The structure formed in HR between the two strands of DNA involved in the HR process.

Explain the logic behind the name 'U snRNA' (used in splicing)

They are SMALL U-rich RNAs that are located in the NUCLEUS. UsnRNA (U-rich small nuclear RNA)

What is a ligand?

The target non-covalent binding molecule of an enzyme.

Define the 'melting temperature' (Tm) for DNA.

The temperature at which 50% of oligonucleotide is still hybridized to its perfect compliment and 50% is dissociated from its complimentary strand.

What is chromatin?

The tightly wound DNA and protein complex that form chromosomes. Combination of DNA and Associated winding proteins.

What is a transition state? How does it affect rate?

The transition state is the state corresponding to the highest energy along the reaction coordinate (grid). It has more free energy in comparison to the substrate or product. The easier (energetically) it is for a molecule to assume the transition state, the faster the reaction.

What is RFLP? How can it diagnose Sickle Cell?

The use of restriction enzymes to discover polymorphisms (variations) in genes. Restriction sites will be present or deleted in genes that vary in sequence. In Sickle cell, one of the MstII restriction enzyme cut sites on Beta-globin has been mutated/knocked out. If you cut the beta-globin gene with MstII, and the middle cut site (pic) is not cut, then it is mutated and patient has sickle cell.

What is z in the Nernst equation?

The valence of the ion in question. Or for our purposes, just its charge. Cl = -1, Na = +1. Ca = +2....etc.

Define Entropy

The variable that determines the direction of all events in the universe. The reason why things don't naturally 'steal' heat from their surroundings, becoming hotter than them.

On which chromosome is the FMR1 gene?

The x-chromosome.

What significance does the arrangement of the globin genes on the chromosomes have?

Their 5'->3' arrangement on the genes corresponds to their temporal expression. In other words the 5'-most globin genes are expressed the earliest in life, the 3'-most the latest.

Why is cholera difficult to vaccinate for?

There are around 300 different serotypes. Hard to pin which one is infecting a population.

Describe the functions of cytoplasmic Ca2+ ion buffers and how these buffers affect cytoplasmic Ca2+ signals.

There are cytoplasmic buffers that sequester the Ca spread from a source and the ER/SR which has internal buffers which allow the ER/SR to absorb and store large amounts of Ca without affecting the concentration gradient. These affect signals by sequestering Ca signals to areas near sources only.

How does the Aminoacyl tRNA synthetase load the correct AA onto the correct tRNA? Does one Aminoacyl tRNA synthetase load all tRNAs?

There are many synthetases, specific to each tRNA. Recognition elements on the synthetase 'read' the anticodon of the tRNA for verification, then load the tRNA with the AA.

A Hydrogen bond in an Alpha helix is formed between the -NH group of one AA and the - COO of another AA. What is the distance between these two amino acids?

There are three amino acids between these two AA. Or in other words the bond is between AA = n and AA = n+4.

What are the different types of secondary active transporters?

There are two basic types of secondary active transporters, those that move different solute species in the same direction (cotransport), and those that move solute in opposite directions (antiport, or exchange).

What is primary cilia and what is its function?

There is one per cell. Non-motile. Organize and promote signal transduction systems (receptors and effectors) that control epithelial cell division, fate (differentiated state), and function. Function was largely unknown until relatively recently.

When speaking of the process of transcription, what is meant with the terms +1, -30, +50?

These are in reference to the distance along the DNA from the start site of transcription. The first base transcribed is the +1 site. There is no value of 0. +1 is first transcribed and -1 is last base un-transcribed.

Outline the unique functions of post-capillary venules.

These are the sites in the vasculature where permeability is controlled in swelling and inflammation. Targets of histamine (inflammatory response) and serotonin. Leukocytes diapedese from this location into the CT as well.

What are the XPB and XPD proteins? What larger factor are they a part of? What is their function?

They are ATP-dependent helicases. Theyre a part of TFIIH

What are some skeletal/body abnormalities in a person with Marfans syndrome?

Too flexible thumb Scoliosis Pectus excavatum - indentation of the sternum

How does hyperglycemia lead to dehydration?

Too much glucose in filtrate of kidneys. Collecting ducts can not reabsorb water into body due to increased osmotic pressure of glucose-rich filtrate. Increased water release.

What is the difference between Topoisomerase I and Topoisomerase II.

Topo I - Cuts one strand at a time Topo II - (shown) Cuts both strands. (Called Gyrase in Prokaryotes)

What enzyme functions to relax super coils in DNA?

Topoisomerase

In what charge direction is depolarization?

Towards a more positive value.

Regarding protein tertiary structure, where are hydrophobic AAs usually located?

Towards the interior. Their hydrophobicity pushes them internal while hydrophilic AAs gravitate toward protein surface.

What is the cellular cause of all of the water secretion in Cholera?

Toxin A (enters via caveolae) -> G-Protein -> upreg of cAMP -> cAMP act on the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) -> loss of Cl- through CFTR -> Water follows ions -> Cell secretes water.

What are the characteristics and functions of Cholera toxins A and B?

Toxin A - active subunit Toxin B - binding subunit There are 5B for every 1 A. Toxin B binds cell surface, A enters cell has pathogenic activity. One can not function without the other.

What is a codominant trait? What is the difference between this and semi-dominance?

Traits are codominant if both traits (alleles) are expressed in the heterozygous state Semi-dominance results when the heterozygous phenotype is intermediate between the two homozygous phenotypes. Codominance is when both alleles are fully expressed individually.

What is the mechanism of gp-41?

Trans Membrane domain (TM) stays bound to viral membrane. FP domain fuses with target membrane. HR1 and HR2 a-helix domains form antiparallel coil (make a hairpin) with one another and pull two membranes together.

Peptide bonds to proline are typically in the Cis or trans position?

Trans. Cis is not energetically favorable.

How is an miRNA produced?

Transcribed in Nucleus. Forms hairpin. Hairpin cut off by Drosha. THEN export from nucleus. Dicer cuts off the hairpin turn leaves RNA duplex with two 3' overhangs. Argonaut binds, selects ONE strand of the duplex. This is now the miRISC complex.

Define Enhancer

Transcription control element that can be either upstream or downstream of transcription start site. Can be up to 50kb away from transcriptional start site. Trans acting elements bind here.

What binds at the Proximal Promotor region? Where is it located?

Transcription factors specific to the gene, not general. Located: 30 - 1000bp upstream of transcription start site.

Iron Regulation: What protein binds Fe for transport into the cell?

Transferrin

Iron Regulation: What protein transports Fe/transferrin complex into the cell?

Transferrin receptor (TFR)

What is Dialysis? What are the two primary types and how they work?

Two types - Hemodialysis and Peritoneal Dialysis. Both filter body of wastes, ionic imbalances, or excess water. Hemodialysis - Take blood from patient. Run blood through tube that is semi-permeable. Tube is soaking in bath, full of Dialyzate. Dialyzte contains the proper ionic concentration (healthy blood) so the blood, will balance its ion concentrations with the dialyzate and reenter the body with proper concentrations. Peritoneal - glucose solution is pumped into the peritoneum. Peritoneum is a semi permeable membrane so toxins seep into glucose solution

What are the types of Gaucher's and their basic characteristics?

Type 1 - Non-neurological, has no neurodegenerative effects. Most prevalent Type 2 - Neurodegenerative. Very early death. Type 3 - Neurodegenerative. Mortality around 30yrs old.

What is a type 1 trans membrane protein and its basic characteristics?

Type 1 - single transmembrane domain, C-terminal is outside ER. Cleavable N-terminal signal sequence

What are types 2 and 3 transmembrane proteins and their basic characteristics?

Type 2 - C-terminal is inside ER, no cleavable N-terminal signal sequence. (+) Chg immediately towards N-terminus from Signal Anchor Type 3 - C-terminal is outside ER, no cleavable N-terminal signal sequence. (+) Chg immediately towards C-terminus from Signal Anchor Note that (+) charged AAs on either side of the signal anchor dictate whether that side of the AA chain will be in the cytosol.

What type of collagen is abundant in the basil lamina?

Type 4

What types of diseases is whole Exome/Genome sequencing useful for? Why?

Typical Mendelian diseases (inherited and expressed via a normal, non-complex pattern). Because many Mendelian diseases pertain to a genetic mutation in a protein coding region that leads to the trait. Can use on a single family with an observably inherited trait, compare exome/genome sequence of affected versus unaffected and see the difference between the two group's exons.

Histologically, describe the appearance of macrophages

Typically larger than other cells with large nucleus. Marked with an M in pic.

Which AA does an RTK phosphorylate?

Tyrosine Its called a receptor tyrosine kinase.

PAH activity turns Phe into what?

Tyrosine.

What are the functions of U1 and U2 snRNAs as well as the U2 associated factor in splicing?

U1 - recognize 5' end of intron (GU), base pair with it. U2 - Recognize branch point (A) of intron. Squeezes out branch point, makes it reactive U2AF - Recognizes 3' splice site of intron (AG)

What are the stop codons? What Amino Acid do they encode?

UAA, UAG, and UGA. They do not encode an amino acid into the peptide chain.

UPD of the paternal PWS/AS loci causes what? UPD of the maternal PWS/AS loci causes what?

UPD Paternal - Angleman UPD Maternal - PWS

What is the most prevalent Carcinogen?

UV

What is UPD (regarding chromosomes)?

Uni-parental Disomy - two copies of one parent's allele for a gene.

A child's parents are both non-syndromically deaf. What are the chances that the child will be deaf?

Unknown. Due to locus heterogeneity the parents could be deaf owing to mutations in two different genes. Two outcomes: 1) Mutation in same gene (say GJB2) child is deaf 2) Mutation in two different loci, child is possibly not deaf depending on which loci (and recessive/dominant nature of mutation)

Which cell up regulates the amount of free Ca++ in the blood stream? Which Downregulates free Ca++? Osteoblast Osteoclast Osteocyte

Upregulate - Osteoclast Downregulate - Osteoblast -clasts degrade bone matrix into Ca++ which is released into the blood stream - blasts generate bone matrix which uses up free Ca++ from the bloodstream.

Where are IRES RNA elements located?

Upstream of the AUG

Where is the 5' UTR located in relation to the primary transcript?

Upstream of the initiation codon.

Where is topoisomerase functioning in normal DNA replication?

Upstream of the replication fork. Helices unwinding DNA causes upstream extreme coiling. Topoisomerase fixes in eukaryotes, (Gyrase in Prokaryotes is Topoisomerase II).

What are the two ways in which our cells acquire cholesterol?

Uptake and Synthesis Uptake - LDL binds LDLR (receptor) and is endocytosed into lysosome. Synthesis - Signals at the surface of ER cause downstream triggering of transcription factors to up regulate cholesterol production by the cell. Uptake and Synthesis proteins have the same promotor and are acted upon by same transcription factor .

Why is myoglobin bad for O2 transport to tissues? Where is it useful?

Useful in lungs were surrounding pO2 is high. Bad in tissues because the pO2 in tissues is low. Myoglobin will not release the O2.

What is pre-implatation genetic diagnosis? Benefits? Drawbacks?

Using parental sperm and egg, growing embryo in lab, biopsy embryo to test for mutation. If embryo healthy/normal then placed into mother for implantation. Benefit - is healthy embryo made from original parental genomic material Drawback - extremely expensive.

The 5' and 3' UTR are not translated into a protein. Can mutations here affect gene expression?

Yes. These regions are largely responsible for stability and regulation of the RNA transcript. Alteration here can be detrimental in these areas.

How does Helicobacter Pylori survive in gastric juices?

Using urease. Urease secreted by the cell raises the pH directly around the cell wall of the bacteria. Allows for survival.

What is meant by a polycistronic mRNA?

Usually in prokaryotes. One mRNA has multiple start codons to be utilized in translation. Different proteins from the same mRNA.

Why are HELA cells important?

Utilized to test methods to turn back on tumor suppressor genes and force HeLa cells into senescence. Future cancer therapy.

What is the equation for the velocity of an enzymatic reaction?

V = k[S] k = rate constant [S] = concentration of substrate

What are the aliphatic (hydrophobic) non-polar Amino Acids?

VAG MIL - yes like it sounds. Valine Alanine Glycine Methionine Isoleucine Leucine

What are the three SNARE proteins discussed involved in vesicle fusion?

VAMP SNAP-25 Syntaxin

What genes does HIF-a accumulation turn on?

VEGF - vascular endothelial growth factor TGF-b - Transforming Growth Factor PDGF-b - Platelet derived growth factor

What is a VNTR? How is it utilized?

Variable Number Tandem Repeats Many areas in genome contain Non-functional repetitive DNA. These areas very in length from person to person. Cutting these apart and visualizing them on a gel gives a fingerprint for the person. Compare VNTR fingerprint to crime scene DNA evidence (or in paternity tests) to see if VNTRs match. Despite a perfect VNTR match to crime scene genomic material, OJ got off the hook.

What is variable expressivity?

Variable expressivity: individuals with the same variant do not show precisely the same disease or quantitative phenotype characteristics.

What is the name for the blood vessel network in the tunica adventitia? What is its purpose?

Vaso Vasorum. Supplies oxygen and nutrients to the adventitia and outer part of the media, as they cannot diffuse to these regions from the blood inside the vessel.

Cardiac muscle is constantly contracting, and in rapid succession. Why is cardiac muscle so resistant to fatigue?

Very large amount of mitochondria (ATP production) and myoglobin. Also has great access to fresh blood supply.

What is a VAMP?

Vesicle Associated Membrane Protein

If RB is AR in expression, how does it come to commonly express in heterozygous patients?

Via LOH.

What is the infectious bacteria in Cholera?

Vibrio Cholerae

What are the difference between SNARES and Viral hairpin binding proteins in their basic binding mechanism?

Viral - ONE protein that is bound to virus envelope, binds target membrane with FP domain and forms its own ANTI-parallel a-helix hairpin to bring membranes together. SNARE - MULTIPLE proteins boud to each the incoming vesicle and the target membrane form a parallel a-helix coiled coil. Brings membranes together.

How can you determine whether hyaline cartilage is growing or not histologically?

Visible chains of chondrocyte clones (circled) where chondrocytes are undergoing mitosis.

In laymans, how does Vm relate to a calculated E in relation to which direction an ion 'wants' to go?

Vm, again is the potential of the inside of a cell. If Vm is negative, the inside is negative, if positive the inside is positive Every ion wants to MOVE the Vm to its own E. So if Vm = -80 and E = -20 the ion wants to do what it can to make Vm = E. (make Vm more positive in this case) So in this case if ion is positive, it will want to go INTO the cell to make -80 more positive (more like -20). If the ion is negative it will want to move OUT of the cell to make the inside of the cell more positive (-80 -> -20)

In regards to enzyme kinetics, what is Vmax? What is 1/2V? What is Km?

Vmax = the fastest a reaction will commence with a given enzyme with a saturation of substrate 1/2V = 1/2 of the Vmax Km = The substrate concentration when reaction rate is 1/2Vmax.

What factor of volume change does a cell undergo in the following conditions (impermeable to both): Cell: 300mM protein in ICF placed into a solution with ECF: 300mM CaCl2

Volume reduced to 1/3 of original. 300mM CaCl2 -> 900mosM 900mosM ECF compared to 300mosM ICF -> cell shrinks to 1/3 original size.

How is VHL classified?

Von Hippel-Lindau disease is classified based on presence or absence of pheochromocytoma and type of VHL mutation. 1. Type 1: Hb + ccRCC Due to total or partial loss of VHL 2. Type 2: PHEO +/- Hb +/- ccRCC i. Type 2A: Hb + Pheo ii. Type 2B: Hb+ Pheo+ ccRCC iii. Type 2C: Pheo only

With are the aromatic (hydrophobic) amino acids?

WYF Tryptophan - W Tyrosine - Y Phenylalanine - F

Describe the physiology behind oral rehydration solutions used in Cholera treatment.

Water with sugar and salt. Increase cellular uptake of ion/glucose to balance efflux of CL-.

Comprehensive slide on siRNA, miRNA, and piRNA

Weeeeee

How do you treat Acute Hyperkalemia?

What do you do when you C BIG K? C: Ca2+ B: Bicarbonate, HCO3-, Alkalanize the blood. (sucking up protons makes cells uptake K+) I: Insulin - increase cellular ATP, more Na/K pump activity, more K into cell G: Glucose - K: Kayexalate - binds up K+, gets it out of the body. OR dialysis

How do miRNA inhibit translation?

When bound they inhibit recruitment of the ribosome. Or they recruit other translational blockers.

Why is therapeutic non-coding RNA therapy more 'exciting' than protein targeting therapeutic mechanisms?

When targeting proteins you must consider structure and how drug interactions with similarly shaped proteins can occur (side effects). With ncRNA therapy all you have to know is the sequence of the target.

What is a dominant negative mutation?

When the mutated protein messes with the function of the WT or normal protein.

What is Euchromatin?

Where genes reside. A More accessible form of chromatin

What is the transition zone in a cilia ?

Where the basal body attaches to the axoneme

In sanger sequencing, does the DNA polymerase reaction that is loaded with the terminating ddATP have regular dATP in it?

Yes, otherwise the DNA polymerase would cut off at the first A laid down in the sequence every time.

Are women who are carriers affected by hemophilia A?

Yes. 10% of them. (thought to be due to x-inactivation)

Is CDK required to drive Mitosis?

Yes. CDK drives all steps of the cell cycle.

A cell is permeable to Cl- ions. [Cl-]o= 110 nM, [Cl-]i= 11 nM, and Vm= -70. Is Cl- pumped? If so, in which direction?

Yes. Pumped in. E = -60 * log(10) = -60. Vm = -70. Cl wants to leak OUT of cell to make Vm more positive (more like E). So Cl must be pumped IN.

The primary transcript contains its UTRs then undergoes splicing. Does the mature mRNA retain its 3' and 5' UTRs?

Yes. The poly AAA and 5' cap are attached to their termini.

Where are the promoter Proximal Elements located?

Within 200 bp upstream of start site. Beyond that distance they may be ineffective

Who does Gefitinib work for? Why does it stop working on that patient group?

Works on patients with single EGFR gene mutations that make EGFR more active. Stops working when mutant EGFR acquires second mutation.

On which chromosome is the gene for dystrophin?

X

On which chromosome is XIST gene?

X chromosome

What is the inheritance pattern, prevalence, and mutation in Duchene's Muscular Dystrophy?

X-Linked 1:3500 males Mutation in Dystrophin gene (DMD)

Distinguish the differences between X-linked dominant and X-linked recessive inheritance.

X-Linked Recessive Phenotype expressed in all males who carry the affected genotype Phenotype expressed in homozygous females only Heterozygote females are carriers X-linked dominant Phenotype expressed in females who carry the disorder Phenotype expressed in all males Phenotype may be so severe in males, it may not be compatible with life

What are Dystrophinopathies? What are some examples?

X-linked recessive disease related to mutations in the dystrophin (DMD) gene Spectrum of muscle disease from mild to severe Duchenne Muscular Dystrophy Becker Muscular Dystrophy DMD-associated dilated cardiomyopathy

What are two scientific tools to elucidate protein structure? In regards to the protein, what do they both require?

X-ray crystallography Biomolecular NMR. Both require large quantities of purified protein.

What is Xeroderma Pigmentosum? What repair pathway must be damaged for this disease to occur?

XP: Sun hyper-sensitiviey, Skin neoplasms NER pathway. No repair of thymine (pyramidine) dimers.

TFIIH contains which component proteins that we discussed?

XPB - helicase XPD - helicase Cdk7 - kinase

What diseases (that we discussed) are associated with mutations in TFIIH? What are their related causes/symptoms?

Xeroderma Pigmentosum - failure of DNA to repair damage caused by UV light. Cockayne's Syndrome - Neurodegenerative. Sensitivity to light. Premature aging Trichothiodystrophy - "bad nourishment" Wasting away, sensitivity to light. Combo of transcriptional defects as well as DNA repair defects.

What cancers are autosomal recessive inherited?

Xeroderma pigmentosa (XP genes), Ataxia-telangiectasia (AT gene), Bloom's syndrome Fanconi's congenital aplastic anemia (FA genes).

RB is an AD disease. Can an unaffected couple have an affected progeny?

Yes Because of the 10% of individuals with the allele that are not penetrant. (90% penetrance, so some don't show it)

Can one tRNA recognize and bind with multiple different codons?

Yes, due to wobble

How can you tell that a chromosome is 'acquired' as opposed to 'constitutional' in someone presenting with an abnormal karyotype?

You have to have comparative data. Best to have a fetal karyotype (amniotic or chorionic) and to compare it in different life stages. Any Chromosomes new to the karyotype after fetal karyotype are 'acquired'

How do you select patients for personalized medicine in lung cancer?

You must biopsy and analyze the specific tumor to ensure that your targeted therapy will work.

What is E if the concentrations of an ion are the same both inside and outside of a cell?

Zero E = RT/zF * ln(Co/Ci) E = RT/zF * ln(1) => RT/zF * 0 = 0

The Androgen Receptor is which class of transcription factor? (based on DNA binding domain)

Zinc Finger

What is a neurofibroma?

a tumor formed on a nerve cell sheath, frequently symptomless but occasionally malignant.

Describe the routes by which Ca2+ is extruded from the cytoplasm (a) into the extracellular space and (b) into the lumen of the ER/SR.

a) 3Na / 1Ca exchanger and PMCA b) SERC ATPase Exchanger uses no ATP PMCA and SERC use ATP.

Which population group is at higher risk for a-thal 1 (--)? And for a-thal 2 (a-)?

a-thal 1 (--) = SE Asia a-thal 2 (a-) = Africa, Mediterranean, Asia.

What results from the following genotypes a-thal 1/a-thal 1 a-thal 2/a-thal 2 a-thal 1/a-thal 2

a-thal 1/a-thal 1 = (--/--) hydrops fetalis a-thal 2/a-thal 2 = (a-/a-) mild anemia, 50% a-globin a-thal 1/a-thal 2 = (--/a-) severe anemia, 25% a-globin

What is a-thal-1 allele? And the a-thal 1 trait?

a-thal-1 = Deletion of BOTH a-globin genes on same chromosome 16 (--). Trait = (aa/--) Mild Anemia

What is a-thal-2 allele? And the a-thal 2 trait?

a-thal-2 = Deletion of ONE a-globin gene on each chromosome 16 (a-). Trait = (a-/a-) Mild Anemia

What hemoglobin tetramer is present from ~ birth onward in a severe b-thalassemia patient?

a4

What is pemphigus?

an autoimmune disease in which antibodies are produced against components of desmosomes in skin, leading to extensive blistering. Desmosomes play a role in the binding of the epithelium to the basal lamina. Destruction of desmosomes results in these two layers separating, causing blisters.

What are the characteristics of small muscular arteries?

basically the same as muscular arteries only they lose the outer elastic lamina and retain the inner. Adventitia merges with surrounding connective tissue.

If gamma-globin is a suitable substitute for beta globin why do we even need beta-globin at all?

b-globin needed to make HbA in adults = essential for pregnancy where fetus must 'steal' O2 from mother with its gamma-globin equipped HbF.

What is beta-zero Thalassemia? And Beta-Plus Thalassemia?

b-zero = NO HbA due to lack of beta-hemoglobin contribution. [Hb] is ~5% of normal level (of which 95% is α2γ2 with 5% α2δ2), which is not enough for good survival. b-plus = Most common form of b-thalassemia. Some b-globin so some HbA present.

What two genotypes give rise to Thalassemia minor?

b-zero heterozygote (b/-) b-plus heterozygote (b/diminished b)

Why can't restriction enzymes cut the product of reverse transcription?

because the product is a DNA/RNA hybrid. Can only cut dsDNA

What type of DNA does reverse transcriptase make?

cDNA

Describe cytoplasmic polarization in an epithelial cell

cytoskeleton, (mostly Microtubules) are polar in their arrangement. Organelles are distributed in a precise polarized pattern; secretory vesicles in the apical domain are usually different from those in the basal domain, and they move in specific directions.

What is a provirus?

double stranded cDNA product of reverse transcriptase activity on viral mRNA that has been incorporated into the genome.

What are the initiation factor proteins in eukaryotic initiation? What do each of them do?

eIF-4E (cap-binding protein) binds to 5' cap. eIF-4G (scaffolding protein) is recruited by eIF-4E. eIF-3, which binds to the 40S ribosome eIF-2, which binds to a tRNA charged with methionine initiates protein synthesis eIF-4A, a helicase to melt any RNA structure encountered

What eukaryotic protein is bound to and guides the initiator tRNA into the A site?

eIF2

Describe the function of the release factors in eukaryotes. What binds where. What causes dissociation of Ribosome.

eRF1/eRF3 compound binds in A site. eRF1 Binds Stop Codon. eRF3 bound to eRF1. GTP bound to eRF3, hydrolysis of this GTP causes ribosome to break apart.

Describe the epithelial to mesenchymal transition during development.

epithelial-mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal cells that can differentiate into a variety of cell types. EMT is essential for numerous developmental processes including mesoderm formation and neural tube formation. EMT has also been shown to occur in wound healing, in organ fibrosis and in the initiation of metastasis for cancer progression.

In regards to genetic mutation, what is 'fitness'? What level of fitness do lethal mutations have?

fitness - a measure of the chance an allele will be transmitted to the next generation (Scale is 0-1). Lethal - fitness = 0. Not able to be passed on due to death of carrier.

Alpha globin is upregulated at 5 weeks post conception. However it is not present in severe a-thalassemia (--/--). So what hemoglobin tetramer is formed between week 5 and birth?

gamma-globin tetramer. Remember epsilonHb -> gammaHb at week 5.

What sphingolipid aggregates in Fabry's disease?

globotriaosylceramide (abbreviated as Gb3)

What results from exocrine pancreatic insufficiency in CF patients?

greasy, bulky, foul smelling stools, failure to thrive and malabsorption nutritional consequences; CF-related diabetes

What is heritability (h^2)?

h^2 = Proportion of observed variance in trait that is due to genetic variation. High h^2 = high link between genetic variation and varying trait Low h^2 = Low linkage between genetic variation and the variance of the trait. A high heritability implies that differences among individuals with respect to a trait such as blood pressure in a population can be attributed to differences in the genetic make- up.

Non-polar amino acids are usually hydrophilic, hydrophobic or neutral?

hydrophobic

What is the measure of the risk of disease in relatives?

lambda (s) = risk of disease in sibs affected / risk of disease in general pop.

What are the characteristics of the following epithelial terms: -Simple -Stratified -Pseudostratified -Squamous -Cuboidal -Columnar -Transitional

layers of cells: Simple epithelia - all cells arranged in a single layer or sheet. -Stratified epithelia - more than one layer of cells in which cells of the outer layers do not directly contact the basal lamina. -Pseudostratified epithelia - some cells do not reach the free surface, but all directly rest on the basal lamina. Cell shape relative to the apical to basal axis: -Squamous - are flattened cells, -Cuboidal - cube-like, -Columnar - taller than they are wide. Stratified epithelia are named according to their outermost layer (e.g. stratified squamous epithelia have a squamous outer layer, though inner cells are often cuboidal). Surface specializations of the outer layer of epithelial cells. -Transitional epithelia - these epithelia are stratified, but when stretched change their shape from cuboidal to squamous, and appear to decrease the layering: this is indicative of a tightly adherent epithelium that is very resilient and stretchable.

How does lncRNA guide proteins to the DNA genome?

lncRNA binds protein and then base pairs with genome. Recruits protein to specific area of genome.

How are lncRNA and small silencing RNA related (general)?

lncRNA can act as the precursor for siRNA and miRNA .

Which small silencing RNA can directly regulate translation?

miRNA

Drosha protein is associated with the processing of what small silencing RNA? Where is it functional?

miRNA. In the nucleus.

Are there more codons or amino acids?

more codons 64 codons and 20 amino acids. Multiple codons encode for the same amino acid.

Where is Collagen 1 located?

most common form of collagen, present in connective tissues.

Describe the full mechanism for Gaucher's disease.

mutation in glucocerebrosidase gene on chr 1 -> deficient glucocerebrosidase activity -> Build up of glucocereborsides in macrophage lysosomes -> formation of Gaucher cells which get stuck in liver and spleen -> Hepatosplenomegaly.

What values for pH and pOH exist in neutrality?

neutrality, pH = pOH. So they both must be 7.

What is the complete molecular mechanism of Type 1 OI?

nonsense frameshift in COL1A1-> LOF of COL1A1 Protein -> unstable mRNA that's degraded -> 50% of normal type 1 collagen produced -> extremely brittle connective tissue.

In relation to genetic mutation, what is a compound heterozygote?

one who carries two different mutant alleles of the same gene.

What is the difference between dNTPs and rNTPs?

only the 2' hydroxyl group. DNA does not have, RNA has. Also Thymine is only a dNTP and Uracil is only a rNTP

What gene is most commonly mutated in Li-Fraumeni Syndrome? What percentage of cases?

p53 ~70%

What aspect of the KDEL receptor mediates its binding and release of KDEL-bearing proteins?

pH pH in ER is different than golgi. Higher pH in ER than golgi causes release of protein.

What is the equation to convert concentration of H+ into pH? And for conversion of [OH-] into pOH?

pH = -log([H+]) pOH = -log([OH-])

What is the henderson-hasselback equation?

pKa = pH + log [acid]/[base] OR another way to think of it pKa - pH = log [acid]/[base] - so if: [acid] > [base] then log [acid]/[base] = pos number, so pKa > pH. If [base] > [acid] then log [acid]/[base] = neg number, so pKa < pH.

What is the Henderson Hasselbalch Equation?

pKa = pH - log([A-]/[HA]) pH = pKa + log([A-]/[HA])

What is pKa? What do high and low values represent?

pKa = strength of an acid/base. Low pKa = Strong Acid High pKa = Strong Base HA <-> H+ + A- pKa = -log([H+][A-]/[HA]) So based on equation, the more a compound breaks apart into A- and H+ (more H+, more acidic) the greater the [H+][A-]/[HA] ratio and the lower the -log value (note the negative symbol)

What is the Hardy-Weinberg equation?

p^2 + 2pq + q^2 = 1 and p + q = 1

What are the 4 most common phospholipids?

phosphatidylethanolamine (PE) phosphatidylcholine (PC) phosphatidylserine (PS) phosphatidylinositol (PI)

Which ISCN location is most proximal to the telomeres? q21.1 q23.4 q24.33 q24.4

q24.4. Numbers increase with increasing distance from centromere and decreasing distance to the telomere.

Phenotypically normal inv(8) carriers can produce an offspring with an abnormal phenotype. What is the term for that offspring?

rec(8). Recombinant 8 - Recombination between inverted and normal homologues occurred resulting in unbalanced genetic products.

What is the most commonly observed RT in humans?

rob(13;14)

What are the 6 different types of alpha-globin genotypes? What does each cause (clinical symptoms and a-globin levels) ?

see Pic for a-globin protein amount, just think that each a-globin gene contributes 25% protein. So: 4a = 100%, 3a=75%, 2a=50% etc....

What are the ranges of CAG repeats in HD for the following classifications? In each case are you affected? Normal Intermediate Variable Penetrance Full Penetrance Juvenile Onset

see pic

About how thick is the lipid bilayer of a plasma membrane?

~5nm

How many genetic variants are there of Hemoglobin?

~600

What is the basic mechanism of APML?

t(15;17) results in the formation of a novel protein transcription factor that acts to repress the cellular response to certain elements thereby blocking differentiation.

What are the two most common translocations associated with Leukemia?

t(9;22), t(15;17)

What is hemoglobin S/C disease?

the HbS/HbC genotype. Mild hemolytic anemia and mild splenomegaly.

What cellular entity degrades Ub marked proteins?

the Proteasome.

What does Diapedesis mean?

the passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation.

What is erythropoiesis?

the process which produces red blood cells (erythrocytes).

What is a hemangioblastoma?

tumors of the central nervous system that originate from the vascular system. Can also occur in spinal cord and retina

What is the function of Dyamin?

wraps the neck formed in vesicle budding and pinches it off.

What percentage of genes in your genome code for channels or transporters?

~10%

What is the carrier frequency of Sickle Cell in African Americans? What is the disease frequency?

~10% - carrier 1/400 - disease

About how many Na ions flow in per action potential per channel?

~1000

How long after birth is the transition from gamma globin to beta globin still taking place in the tetramer?

~2 months.

What percentage of VHL cases are due to new mutations? (non inherited)

~20%

About how long is the 3' poly A tail? (How many A's?)

~200 bp

What are the various functions of lncRNA?

• Subcellular localization signals • Molecular scaffold • Nucleic acid interaction and targeting • Protein interactions • RNA catalysis

What is the most common mutation in CF?

∆508F in the CFTR gene.

How is ∆E calculated?

∆E = E (e acceptor) - E (e donor) And ∆G = -nF∆E So positive values for E(e Acceptor) and negative values for E(e donor) result in larger positive ∆E and therefore larger NEGative value for ∆G, resulting in more favorable reaction thermodynamics.

What is genetic cause of CF?

∆F508 (deletion of a phenylalanine at position 508) in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. -> Defective CFTR

What are the two equations for Gibbs free energy for chemical reactions (Involves Equilibrium Constant)?

∆G = ∆G0 + RT ln [PRODUCTS]/[REACTANTS] ∆G0 = - RT ln(Keq)

What is the equation for Gibbs free energy for chemical reactions (involves enthalpy)?

∆G = ∆H - T∆S H = enthalpy S = Entropy T = Temp in KELVIN Also Change in G = G (products) - G (Reactants)