Bio quiz 2

What is the ENCODE project?

-Encyclopedia of DNA Elements -Trying to understand why/how we can create more proteins

H1N1 pandemic

-first seen in US in spring of 2009 -highly contagious, spreads from person to person like seasonal flu -worldwide spread -most cases are mild to moderate -complications in high risks groups such as pregnant women, young children, diabetes, asthma, heart disease, etc)

diploid/haploid/tetrad

2

Diploid (2n)

2 sets of chromosomes

What were the surprises from the Human Genome Project - 2003?

25,000 genes in the genome ("protein coding"). 1000s genes produce noncoding RNAs. Reported 706 genes noncoding RNA genes

In the Hershey Chase experiment, why were 32P and 35S used?

35S-proteins 32P-DNA Used to mark the two things

What were the surprises from the ENCODE Project?

>80% contains elements linked to biochemical function. Not junk! This high 80.4%, very controversial at the time. 18,400 RNA genes/20,687 protein-encoding genes ~1-2% of genome (2018: 25,525 RNA/21,306 protein encoding). 76% of genome transcribed into RNA as end-product, not protein. RNA is the functional unit of genome & fundamental unit of heredity. 5% of human genome conserved across mammals. 4% of human genome, not conserved across mammals, is conserved between individuals, i.e., human lineage. 42% of genome accessible by transcription factors (TFs). Evolution can occur by selection for RNA sequences that alter gene regulation, not just selection for protein sequences.

Karyotype

A display of the chromosome pairs of a cell arranged by size and shape.

cystic fibrosis

A genetic disorder that is present at birth and affects both the respiratory and digestive systems.

Actin

A globular protein that links into chains, two of which twist helically about each other, forming microfilaments in muscle and other contractile elements in cells.

DNA ligase

A linking enzyme essential for DNA replication; catalyzes the covalent bonding of the 3' end of a new DNA fragment to the 5' end of a growing chain.

G0 phase

A nondividing state occupied by cells that have left the cell cycle, sometimes reversibly.

kinetochore

A specialized region on the centromere that links each sister chromatid to the mitotic spindle.

Codon

A specific sequence of three adjacent bases on a strand of DNA or RNA that provides genetic code information for a particular amino acid

epidemic

A widespread outbreak of an infectious disease.

How does prokaryotic gene regulation differ from eukaryotic?

Ability to change metabolic activities in response to the environment. •Capability to induce entire enzyme pathways.

Aneuploidy

Abnormal number of chromosomes.

Purines

Adenine and Guanine

What are some examples of gene regulation after transcription?

Alternative splicing: Some transcripts can undergo alternative splicing, making different mRNAs and proteins from the same RNA transcript1. miRNAs and siRNAs: These small RNA molecules can bind to mRNA and prevent its translation into protein1

DNA helicase

An enzyme that unwinds the DNA double helix during DNA replication

Heterozygous

An organism that has two different alleles for a trait

Homozygous

An organism that has two identical alleles for a trait

Phenotype

An organism's physical appearance, or visible traits.

antigenic drift vs antigenic shift

Antigenic drift: mutations within genome Antigenic shift: Reassortment of new viral genome segments

somatic cells

Any cells in the body other than reproductive cells

autosome

Any chromosome that is not a sex chromosome

Centromere

Area where the chromatids of a chromosome are attached

Erin Chargaff

Austrian Biochemist, the amounts of adenine, thymine, guanine, and cytosine were not found in equal quantities, and that it varied from species to species, but not inbetween individuals of the same species

What are BRCA1 and BRCA2?

BRCA1 and BRCA2 mutations are typically seen in cases of hereditary ovarian cancers. Overall, it has been estimated that inherited BRCA1 and BRCA2 mutations account for 5 to 10 percent of breast cancers and 10 to 15 percent of ovarian cancers among white women in the United States.

Epidemiology

Branch of medical science concerned with the incidence, distribution, and control of diseases that affect large numbers of people.

Chemotaxis

Cell movement that occurs in response to chemical stimulus

transcription factors

Collection of proteins that mediate the binding of RNA polymerase and the initiation of transcription.

What is the benefit of sequencing the genomes of many different species?

Conservation genomics of endangered species sequenced. and see where we came from, we can look into the past and see where stuff came from.

What are transcription factors and why are they important for eukaryotic gene expression?

Control sequences can be distant from the promoter & gene. they can be activators or silencers.

What 4 meiotic mechanisms provide genetic diversity?

Crossing Over Independent Orientation Homologous chromosomes Fertilization is random

shotgun sequencing

Cutting DNA into random fragments and then determining the sequence of bases in each fragment

Pyrimidines

Cytosine and Thymine

Why are defects in mitosis more relevant to cancer than other genetic diseases?

DNA mutations, rearrangements, deletions, amplifications, & addition or removal of chemical modifications

DNA versus RNA

DNA: contains thymine, doesn't leave nucleus, generally double stranded, sugar is deoxyribose, provides information for RNA RNA: contains uracil, leaves the nucleus, generally single stranded, sugar is ribose, provides information to proteins

Linus Pauling

Discovered the alpha helix structure of proteins, thought DNA was triple stranded

Pandemic

Disease that occurs over a wide geographic area and affects a very high proportion of the population.

DNA polymerase

Enzyme involved in DNA replication that joins individual nucleotides to produce a DNA molecule

Why are cancers more common in older adults?

Errors that are not corrected form mitosis carry over and stack over time

Explain why mammals require X-chromosome inactivation?

Female mammals inherit two X chromosomes (XX) but do not make 2X the protein from genes on the X chromosome. •One X chromosome in each somatic cell is inactivated (random). •Chemically modified (methylation) & highly compacted.

Who holds the patent for CRISPR and why?

Feng Zhang & Broad Institute first one to invent a technology

cell cycle checkpoints

G1, G2, M Points of transition between different phases of the cell cycle, which are regulated by cyclins and cyclin-dependent kinases (Cdk's).

X-linked genes

Genes found on the X chromosome.

Vertebrate Genome Project

Goal to generate near error-free reference genome assemblies of 70,000 extant vertebrate species.

sister chromatids

Identical copies of a chromosome; full sets of these are created during the S subphase of interphase.

What have we learned from The Cancer Genome Atlas (TCGA) Project?

Identified 20 cancer targets / now 33 types Most cancers caused by 2-8 sequential alterations over 20-30 yr. chromothripsis or "chromosome shattering" can occur and and it is much more frequent than originally thought. Occurs in >50% in several cancer types (soft-tissue).

epigenetic inheritance

Inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence.

What is the power of the "Count Me In" project regardless of whether you would want to participate?

It can jump start conversations.

What is the promise of artificial intelligence/machine learning in cancer diagnosis & treatment?

It hopes to make the proves faster, and more acerate. To diagnose it earlier

What is the value of using a pedigree to track genetic traits and what it cannot determine?

It shows the physical traits by passing down. It can't determine any genetic mistakes or hidden mistakes that haven't been recorded.

Was the ruling against Myriad good or bad in the long run? What are the implications from a business perspective?

It was a good thing in the long run. Form a business perspective its a bad thing. They cant really make a profit off of it

Who won the 2018 Novel Prize in Medicine and what was their novel hypothesis that changed how cancer is treated?

James P. Allison use a person's immune system to fight the cancer.

Who won the Nobel Prize for CRISPR-Cas9?

Jennifer Doudna and Emmanuelle Charpentier

What is the benefit of human genomic information?

Knowing our past, and seeing what causes genetic diseases.

How is the lac operon controlled versus the trp operon?

Lac operons blocks when there isnt any trp operon: bocks if there is to much

Hypoxia

Low oxygen saturation of the body, not enough oxygen in the blood

Genetic diversity that occurs through meiosis is different from diversity that is generated through evolution. Explain.

Meiosis produces changes in diversity faster on a small scale with small changes through species. Diversity generated by evolution is more on a slower scale that does major changes over a slower time.

Explain X-linked inheritance and why do sex-linked disorders affect mostly males?

Men need to inherit only one copy of the recessive allele for the condition to be fully expressed.

Law of Segregation

Mendel's law that states that the pairs of homologous chromosomes separate in meiosis so that only one chromosome from each pair is present in each gamete

What is epigenetic regulation and mechanistically, how does it control gene regulation?

Modifications to DNA molecules that do not change DNA base sequence but can affect gene expression. chemical modifications can be inherited although the DNA sequence is not altered.

immune checkpoints

Molecules that either stimulate or inhibit T cells - Critical for maintaining self-tolerance and modulating duration/amplitude of immune responses to minimize collateral damage

What are the advantages of using a genome graph rather than a single reference genome?

More accurate, more complete genome sequences. Ability to identify unique variants between individual genomes. May identify mutations missed by sequence comparison to single reference genome. Captures regions that were not identified previously because of insertions, duplications, and/or deletions.

How is herd immunity acquired?

Most of pop vaccinated

Why are cancers associated more often with tissues of epithelial origin?

Of its high exposer to the environment

What is RNA splicing?

RNA splicing: sequences called introns are cut out, sequences called exons are kept and and spliced (joined) together.

What are some examples of gene regulation at the transcription level?

Spliceosome: large RNA protein complex Drosophilia: 1 gene can generate 17,500 proteins

What drives new emergent and re-emergent infectious diseases?

The consatnt mutation

G1 phase

The first gap, or growth phase, of the cell cycle, consisting of the portion of interphase before DNA synthesis begins.

G2 phase

The second growth phase of the cell cycle, consisting of the portion of interphase after DNA synthesis occurs.

metastasis

The spread of cancer cells beyond their original site

S phase

The synthesis phase of the cell cycle; the portion of interphase during which DNA is replicated.

Why are genetic disorders based on multiple gene involvement so difficult to diagnose and treat?

They are rare, it's a Heally gene mess up so it will be passed down.

What can a karyotype reveal and what can it NOT reveal?

They can reveal what chromosomes and the amount. genetic disorders. It cant reveal changes on the DNA lv

Why are so many of the infectious emerging diseases due to RNA viruses?

They mutate a lot faster.

Why do eukaryotes require cell differentiation?

They to become specialed structures

How will treatment of cancer change as the Cancer Genome is exploited?

Treatments that use a person's immune system to fight the cancer Chemotherapy: nonspecific, kills or slows the growth of fast-growing cells but also healthy cells like those responsible for regenerating gastrointestinal lining. Better surgery

Maurice Wilkins

Used X-ray crystallography to study the molecular structure of DNA. Worked with Franklin (did not collaborate well) to create a picture of the DNA molecule which allowed Watson and Crick to deduce the double helix structure of two strands.

DNA viruses

Usually double stranded (ds) but may be single stranded (ss) Circular or linear

Why do species have so many genes in common?

We all have common ancestors.

What are the advantages of being able to predict virulence of human pathogens?

We can know befor it gets to bad or stop befor it becomes a problem

Rosalind Franklin

Woman who generated x-ray images of DNA, she povided Watson and Crick with key data about DNA

William Astbury

X-ray diffraction analysis showed that DNA is a polymer of stacked bases

Autism Spectrum Disorder

a disorder that appears in childhood and is marked by significant deficiencies in communication and social interaction, and by rigidly fixated interests and repetitive behaviors

lac operon

a gene system whose operator gene and three structural genes control lactose metabolism in E. coli

sickle cell anemia

a genetic disorder that causes abnormal hemoglobin, resulting in some red blood cells assuming an abnormal sickle shape

What is the Sanger method of DNA sequencing?

a method of DNA sequencing based on the selective incorporation of chain-terminating dideoxynucleotides by DNA polymerase during in vitro DNA replication

What is an operon?

a unit made up of linked genes that is thought to regulate other genes responsible for protein synthesis.

precision medicine

an approach to disease treatment and prevention that accounts for individual variation in genes and environment

EIDs

are infections that recently appeared or whose incidence or geographic range is rapidly increasing or threatens to increase in the future.

Why do cancers arise more often from somatic cells than germline or gametes?

because cells that turnover frequently.

Oncogenes

cancer causing genes

epigenetic regulation

changes in gene expression that are due to environmental effects rather than to changes in the nucleotide sequence of the gene

CAR T cells

chimeric antigen receptors; activated in laboratory to fight cancer cells

genetic code

collection of codons of mRNA, each of which directs the incorporation of a particular amino acid into a protein during protein synthesis

endemic

confined to a particular country or area

What are the potential ethical issues associated with genomics studies?

could be used for disclination and other stuff

Mary-Claire King

discovered the BRCA1 gene that causes breast cancer

James Allison and Tasuku Honjo

discovery of cancer therapy by inhibition of negative immune regulation

germline cells

eggs or sperm cells that carry genetic instructions to organisms of the next generation

What is the dicer gene and its role in vivo?

essential for generation of miRNAs in mammals. •If it is knocked out, results in embryonic death.

Angiogenesis

formation of new blood vessels

Genotype

genetic makeup of an organism

Genome 10K Project

genomics project to sequence 10,000 vertebrate genomes

What holds the DNA anti-parallel strands together?

hydrogen bonds

Zoonotic diseases (zoonoses)

infectious diseases that humans acquire from animal sources

autosomal dominant

inheritance pattern of a dominant allele on an autosome

noncovalent interactions

interactions that do not involve the sharing of valence electrons

Explain alternative mRNA splicing and how it can generate diversity?

introns are removed & exons spliced together

What is CRISPR-Cas9? What is its power and the ethics of its use?

is a defense system bacteria use to protect against invading genetic elements cleave target DNA with remarkable precision. Add, remove, or modify DNA with precision

What is the role of non-coding RNAs (miRNA & siRNA)?

miRNA: regulate proper level of translation of mRNAs. siRNA: hybridizes perfectly with target., similar to miRNA but double. Acts to silence gene expression.

M phase

mitosis and cytokinesis

Epigenome

overall pattern of chromatin modifications possessed by each individual organism

Gene expression in eukaryotes can occur at multiple levels. Explain.

proteins interacting with DNA turn genes on and off. ••E. coli as model organism to understand prokaryotic gene expression. Ability to change metabolic activities in response to the environment. •Capability to induce entire enzyme pathways.

RNA viruses

replicated and assembled in the cytoplasm

DNA polymerase III

synthesizes new DNA only in the 5' to 3' direction

Proto-oncogenes

the corresponding normal cellular genes that are responsible for normal cell growth and division

What is crossing over and why is it important?

the exchange of genetic material between homologous chromosomes, allows for genetic variation

law of independent assortment

the law that states that genes separate independently of one another in meiosis

Central Dogma

theory that states that, in cells, information only flows from DNA to RNA to proteins

Trp operon

tryptophan binds to the repressor protein and enables it to repress gene transcription.

Autosomal Recessive Inheritance

two recessive alleles must be present for trait to be displayed

Robert Corey

used x-ray to discover alpha-helices and beta-sheets -worked with Linus Pauling

What are the global strategies to keep ahead of the infections and potential pandemic?

vaccines

What have we learned in the last 20 years about the Human Genome?

~8% of the genome was not previously read. It was "hidden". Highly repetitive sequences that previously dismissed as junk. Included the centromeres, hold the DNA strands together. Discovered new genes that help species adapt. Problem because genomes include those from father & mother. Bypassed this problem by studying a rare cell line that has 2 copies from father & none from mother. New sequencing technologies to sequence each chromosome from end-to-end. Discovered new gene variants: now figure out their significance. Found complex patterns of variation thought linked to our rapid evolution. Apply technologies to sequence genome with different chromosome from each parent. Beginning pan-genome effort to read the entire DNA sequences of hundreds of people around the world.

How can the CDC and WHO predict?

•Consider interspecies transmission & re-assortment of viral genome human-to-human transmission •Global perspective: How do you predict the next pandemic? •We can watch virus evolution. -large-scale sequencing, bioinformatic analysis, genomic approaches -experimentally test recombinants for pathogenicity -focus on the hotspots of disease outbreaks at the site of outbreak

targeted protein degradation

•Inactivating proteins is just as important for proper cell function as activating them in the first place •We've seen phosphorylation, dephosphorylation, GTP hydrolysis, etc. as mechanisms for protein inactivation •A common (and permanent) way to inactivate proteins is to specifically target them for proteolytic degradation