Final

What is the purpose of using RNAi in gene therapy?

RNAi silences the genes by destroying the transcript from the invading virus

What is non-allelic homologous recombination (NAHR)

Recombination between misaligned DNA repeats, either on the same chromosome, on sister chromatids or on homologous chromosomes. NAHR generates recurrent deletions, duplications, or inversions

What is thought to be the significant contributor to the variability of CYP3A4 between individuals?

Regulatory mutations due to it being inducible

List ten common characteristics of cancer cells

Self-sufficient in growth signaling, unresponsive to growth-suppression signals, circumventing apoptosis, replicative immortality, genome instability, triggering angiogenesis, tissue invasion and metastasis, immune system evasion, inducing tumor-promoting inflammation, redirecting energy metabolism.

What amino acids are in the hydroxyl group

Ser, Thre, Tyr

What is the most common type of pathogenic mutation

Single nucleotide substitutions

What type of mutations contribute predominantly to cancers?

Somatic (post zygotic)

What are the two types of gene therapy

Somatic; germ-line

Define augmentation therapy

Something given to the patient that supplements a depleted or missing factor to overcome the deficiency and restore function

What is gene therapy

The the direct genetic modification of cells to achieve a therapeutic goal

Where are many of the mutated DNA variants inherited from out parents located. Should we be concerned that they are pathogenic?

They are located in non essential genes. No because they are mutation in common variants such as ABO blood group gene

Why are pathogenic point mutations in noncoding DNA are generally difficult to identify?

They are much less evolutionarily conserved than coding DNA

Why can unequal crossover (UEC) and unequal sister chromatid exchange (UESCE) lead to disease formation

They cause reciprocal exchanges between misaligned chromatids: one chromatid gains an extra DNA sequence, and the other loses an equivalent sequence. Disease may result from a change in gene copy number, or through the formation of hybrid genes that lack some of the functional gene sequence.

How do large scale mutations lead to disease?

They either adversely change the structure or copy number of genes, or they adversely alter gene expression.

What is the purpose of quantitative fluorescence PCR?

To scan for aneuploidy in fetal DNA

What is comparative genome hybridization used for?

To screen for changes in copy number of subchromosomal regions

Define primordial germ cell

The cells that are set aside in the early embryo to give rise to the germ line.

Why can't augmentation therapy be used for diseases caused by a positive harmful effect?

The disease can't be corrected by administering normal genes, products are cells to the patient.

How does a low drug metabolizing rate effect effect an individual's response to normal drug dosage?

The drug concentration will build up, leading to drug toxicity

What does activation of cryptic splice sites produce?

Truncated or extended exons

Treating DNA with sodium bisulfate allows for differentiation of what?

Unmethylated cytosines from meythylated cytosines. This is helpful when using restriction nucleases will cleave sites containing a CpG dinucleotide only if the cytosine is unmethylated.

Describe the process of chromosome microarray analysis?

Using microarrays with oligonucleotide probes from across the genome to scan for subchromosomal changes in copy number and/or single nucleotide polymorphisms

What is the net result of nonsense and frame shifting mutations

The mRNA is degraded via nonsense mediated decay or is translated to give a truncated protein

Define transfection

The nonviral transfer of DNA, RNA, or oligonucleotides into human or other animal cells

The frequencies of single nucleotide substitutions that are silent and those that cause and amino acid to be replaced is based on what?

The position in a codon

Why are mutations at splice junctions, notably changes in the conserved GT and AG dinucleotides at the extreme ends of introns easy to ID even though it is a noncoding region of DNA?

The region is evolutionarily conserved

Which, if any, of the following statements, is false? A null allele is one where the gene has been deleted or received an inactivating mutation causing complete loss of gene function. Inactivating point mutations are a common cause of pathogenesis in recessively inherited disorders. Inactivating point mutations are a common cause of pathogenesis in dominantly inherited disorders. When a gain-of-function allele is known to be pathogenic in a single gene disorder, a heterozygote will always show disease symptoms.

When a gain-of-function allele is known to be pathogenic in a single gene disorder, a heterozygote will always show disease symptoms.

What is a premutation

When an expanded array of repeats is unstable but not big enough to cause disease

Define haploinsufficiency

When the a loss of function of one allele causes a phenotype in the presence of a working normal allele

Which of the following statements, if any, is false? a) Gene therapy involves the direct genetic modification of the cells of a person (or animal model) to achieve a therapeutic goal. b) Current gene therapy is directed at modifying somatic cells. c) The only successful gene therapies are those in which cells are removed from a patient, genetically modified, and then returned to the patient. d) Gene therapy successes have largely involved treatment of recessively inherited disorders.

C) The only successful gene therapies are those in which cells are removed from a patient, genetically modified, and then returned to the patient. There have been some successes with in vivo gene therapy as well as ex vivo gene therapy.

tobacco preferentially causes what mutational signature?

C:G -> A:T transversions in lung cancer

UV radiation preferentially causes what mutational signature?

C:G -> T:A transitions in melanoma

What type of repeats lead to polyglutamine expansions and dynamic mutations

CAG

_______ deficiency shows marked differences between different ethnic groups, as revealed by the frequency of poor metabolizers; poor metabolizers require a lower dose of certain drugs such as clopidogrel, an antiplatelet agent that is used to inhibit blood clotting in some diseases such as coronary artery disease

CYP2C19

_______ deficiency is important in metabolizing the anticoagulant warfarin (as described below), and also results in an exaggerated response to tolbutamide, a hypoglycemic agent used in treating type 2 diabetes.

CYP2C9

What cells are said to be totipotent

Cells from the very early mammalian embryo

Pathogenic splicing mutations are most likely to occur on sequences that specify (cis/trans) acting RNA elements

Cis

What type of chromosome abnormality arises as a result of an abnormal sperm or egg, through abnormal fertilization, or through an abnormal event in the very early embryo

Constitutional

What amino acids are in the polar sulfhydryl group

Cys

What is the concern in pharmogenetics

How the actions of drugs and the reactions to them vary according to variation in the patient's genes

Which of the following is a disease whose molecular basis is due to the unstable expansion of CAG repeats encoding polyglutamine? Hand-foot genital syndrome Oculopharyngeal muscular dystrophy Huntington disease Synpolydactyly type II

Huntington disease

At what phase of clinical trials is the pharmacodynamics of a drug tested?

I

Monooxygenases are found in what reaction phase of drug metabolism

I

How can a frameshift mutation lead to a premature termination codon

If a different reading frame is used, an in frame premature termination codon can be quickly encountered

What is a downside to clinical genome sequencing?

In each person a significant number of variants will be identified whose clinical significance is uncertain. concerns include the question of how to deal with incidental findings in which pathogenic variants are identified that are unrelated to the disorder for which the genome sequencing test was ordered.

What is an example of an inverted repeat leading to disease

In hemophilia A where a large inversion that disrupts the F8 gene, which makes blood clotting factor VIII

Describe the two hit paradigm

It explains why certain tumors can occur in hereditary or sporadic forms. In the hereditary form, the "first hit" involves an inactivating mutation in a tumor suppressor gene that is inherited. The "second hit" occurs in somatic cancer progenitor cells. The combination of the inherited mutation and the somatic mutation causes a mutation in two alleles, leading to tumorigenesis. An example of this is seen in retinoblastoma, a cancer of the eye. Those that have bilateral tumors often transmit the disorder to their children, but those with unilateral tumors do not transmit the disorder to their children.

Describe the principle of gene conversion

It is a non reciprocal sequence exchange between two related sequences that may be alleles or non allelic. - Sequence info is copied from one of the paired sequences to replace and equivalent part of the other sequence

Describe the process of comparative genome hybridization

It labels a test DNA sample and an normal control sample with different fluorophores . They are hydrized at the same time to a defined oligonucleotides probes on a microarray

Describe the principle of the right to an open future

It respects an individual's autonomy and requires that information on non-actionable genetic variants in a child that confer susceptibility to late-onset disorders should not be disclosed before the child becomes an adult and subsequently wishes to obtain that information

What is/are con(s) of nonviral delivery?

Low-level transgene expression

Which of the following amino acid substitutions would be considered to be a conservative substitution if the original amino acid was Arg? Lysine (Arg), (R) Serine (Ser), (S) Tyrosine (Tyr), (Y) Glutamine, (Gln), Q

Lysine (Arg), (R)

What type of point mutations are harder to see

Missense mutations and small non frameshifting deletions/insertions

What types of human cells are naturally polypoid

Muscle fibers that form recurrent cell fusions that result in multinucleate syncytial cells.

(NAT1/NAT2) is polymorphic in a wide range of human populations, with rapid acetylators (who eliminate drugs rapidly) and slow acetylators

NAT2

Concerning transport of genes into human (or animal) cells, which, if any, of the following statements is false? a) Transduction means using viruses to transfer DNA into human (or other animal) cells. b) Tropism refers to the ability of certain viruses to transduce only certain types of cell, such as hepatocytes, but not neurons. c) Tropism depends on a virus being able to recognize a specific receptor molecule on the surface of the cell. d) Transfection means transferring DNA into the cells by any means other than using viruses.

None

Explain why mitochondrial DNA disorders are so significant

Pathogenic mutations are found in at least 1 in 200 of the population, relating mtDNA as a significant cause of human disease. There are no effective treatments for it either, and with such a big number of the population being affected by it, the impact it has is astronomical.

What a the reason natural selection appears to have driven an increase in frequency of the slow-acetylator phenotype in some populations?

certain chemicals in well-cooked meat are converted by NAT2 into carcinogens; individuals with slowacetylator phenotypes would be comparatively protected in populations that have had a long tradition of eating well-cooked meat

Define Chromothripsis

chromosome breakage that can involve an extensive localized rearrangement of chromosomes generated in what appear to be single catastrophic events.

Describe beneficence in terms of genetic testing in children?

genetic testing in children should be of benefit to the child: it should test for clinically relevant and actionable genetic variants only (that is, variants whose results might lead to some kind of beneficial clinical intervention).

(Somatic/germ line) therapy is achieved by modifying the DNA of a gamete, zygote, or early embryo

germ line

(Somatic/germ line) therapy produce a permanent modification that can be transmitted to descendants

germ line

_______ is a protein dimer that is involved with forming complexes with hMutS and DNA, and also contributes PSM2 endonuclease to make nick.

hMutLa

______ is a protein dimer that is involved with recognizing short insertions/deletions cause by replication slippage.

hMutSB

_____is a protein dimer that is involved with recognizing base-base mismatches and single nucleotide insertions/deletions.

hMutSa

In (direct/hairpin) siRNA therapy RNA-mediated siRNA has viruses ferry an artificial gene construct into cells

hairpin

Define mixoploidy

having two or more genetically different cell lineages within one individual

The (highest/lowest) mutation frequencies are found in cancers that have a mutation in their ability to repair replication errors.

highest

Define pharmacodynamics

how the person is affected by the drug

Define analytic validity

how well the assay measures what it claims to measure.

Increase in parental age (increases/decreases) frequency of genetic disorders

increases

What is the role of p53

inhibits excessive cell proliferation and also acts as the guardian of the genome, Suppress tumor growth

How can hypomethylation lead to cancer

may produce aberrant transcriptional expression of highly methylated DNA sequences that will result in chromosomal instability

Gain of function missense mutations in the RET gene which encodes a tyrosine kinase protein result in .... Hirschsprung's disease Downs syndrome Kliefelter syndrome medullary thyroid carcinoma or multiple endocrine neoplasia

medullary thyroid carcinoma or multiple endocrine neoplasia

splicing mutations are especially common in what cancers

myelodysplastic syndrome and chronic lymphocytic leukemia.

Define transgene

nucleic acid molecule introduced as a cloned gene, but sometimes RNA or oligonucleotides into a patient

(tumor supressor genes/oncogenes) are dominantly acting cancer genes that result from an activating mutation in one allele of a cellular proto-oncogene.

oncogenes

(tumor supressor genes/oncogenes) work in growth signaling pathways to promote cell proliferation or inhibit apoptosis

oncogenes

Describe the nondisjunction mechanism of producing aneuploid cells

paired chromosomes fail to separate (disjoin) during meiotic anaphase I and migrate to the same daughter cell, or sister chromatids fail to disjoin at either meiosis II or mitosis.

Deletions in mtDNA contributes to what disease

parkinsons

What type of mutation is the most frequent contributor to disease

point

This type of expansion is not polymorphic and the level of expansion in disease is very modest

polyalanine

This type of expansion is has significant length polymorphism but after a certain length the expansion becomes unstable.

polyglutamine

A mutation that does not cause a disease but that is unstable at mitosis and meiosis and can change into a pathogenic mutation. a post-zygotic (somatic) mutation a missense mutation a dynamic mutation a premutation

premutation

What is Multiplex ligation-dependent probe amplification

rapid way of scanning for copy number changes in defined sequences of interest such as deletions or duplications of individual exons

Where do most repeats involved in triggering large-scale mutations occur?

Within introns or outside genes, and sometimes within coding sequences

A pathogenic mutation that is unstable at mitosis and meiosis and can result in progressively severe phenotypes. a post-zygotic (somatic) mutation a missense mutation a dynamic mutation a premutation

a dynamic mutation

What is Robertsonian translocation (centric fusion)

a highly specialized reciprocal translocation in which exchange of centric and acentric fragments produces a dicentric chromosome that is nevertheless stable in mitosis.

A class of mutation that is quite frequently associated with a gain of function. a post-zygotic (somatic) mutation a missense mutation a dynamic mutation a premutation

a missense mutation

Define haploinsufficiency

a model of dominant gene action in diploid organisms, in which a single copy of the standard allele at a locus in heterozygous combination with a variant allele is insufficient to produce the standard phenotype. Haploinsufficiency may arise from a de novo or inherited loss-of-function mutation in the variant allele, such that it produces little or no gene product.

What do dominant negative mutations result in?

a mutant gene product that somehow impairs the activity of the normal allele in a heterozygote

What is a chimera in terms of genetics

a person with different cell populations that originate from different zygotes

A type of mutation that results in genetic mosaicism. a post-zygotic (somatic) mutation a missense mutation a dynamic mutation a premutation

a post-zygotic (somatic) mutation

Regarding chromosome abnormalities, which of the following statements, if any, is false? a) A Robertsonian translocation is a common example of an aneuploidy. b) Nondisjunction is a common cause of aneuploidy 4 c) Triploidy is most commonly caused by fertilization of an egg by a diploid sperm. d) Tetraploidy is usually due to replication of the zygote's DNA without cell division.

a) A Robertsonian translocation is a common example of an aneuploidy. c) Triploidy is most commonly caused by fertilization of an egg by a diploid sperm. (A Robertsonian translocation is a common example of a structural chromosome abnormality, not an aneuploidy (which involves a change in chromosome number). Treiploidy is most commonly due to fertilization of an egg by two sperms. )

Concerning stem cells, which of the following statements is incorrect? a) Stem cells occur frequently in our bodies. b) A stem cell can divide asymmetrically to give a daughter stem cell plus a daughter transit amplifying cell that can undergo a series of differentiation steps to give rise to a differentiated cell. c) If for any reason, stem cells are depleted, a stem cell can divide symmetrically to regenerate the stem cell population. d) In an adult person, stem cells are normally multipotent or unipotent.

a) Stem cells occur frequently in our bodies.

Which, if any, of the following statements is false? a) The p53 tumor suppressor regulates the G2-M transition in the cell cycle by inhibiting the CDK2-cyclin E complex. b) p53 regulates the CDK2-cyclin E complex by stimulating the p21 tumor suppressor. c) The CDK2-cyclin E complex relies on stimulation by the E2F transcription factor. d) The RB1 protein normally binds the E2F transcription factor to prevent it working and so acts as a brake on the cell cycle

a) The p53 tumor suppressor regulates the G2-M transition in the cell cycle by inhibiting the CDK2-cyclin E complex. (p53 regulates the G1-S transition in the cell cycle.)

Which of the following descriptions, if any, is false? A person's ability to absorb or metabolize a drug that is intended to treat a genetic disorder a) is entirely due to genetic factors. b) depends on a person's lifestyle. c) is not modified by having a bacterial infection. d) is independent of a person's diet

a) is entirely due to genetic factors. c) is not modified by having a bacterial infection. d) is independent of a person's diet.

How does aberrant DNA methylation effect cells? a. Hypomethylation leads to inappropriate expression of highly repetitive DNA sequences b. Hypomethylation silences tumor suppressor genes c. Hypermethylation leads to chromosome instability d. Hypermethylation is linked to adenomas

a. Hypomethylation leads to inappropriate expression of highly repetitive DNA sequences

What is the cause of chimerism

aggregation of fraternal twin zygotes or immediate descendant cells within the very early embryo.

What are intrabodies?

antibodies but they only have a single polypeptide chain instead of the typical four polypeptide chains of a normal antibody. These types of antibodies are important because they are well suited for intracellular activities

How can hypermethylation lead to cancer

at promoters leading to silencing of tumor suppressor genes, DNA repair genes, and genes encoding certain transcription factors that are important in differentiation

Which, if any, of the following can be classified as a type of augmentation therapy? a) Treatment using a small molecule drug to bind a target protein and prevent it working. b) A bone marrow transplant. c) Corrective surgery for cleft lip and palate. d) Insulin treatment in diabetes.

b) A bone marrow transplant. d) Insulin treatment in diabetes.

(Recessive/dominant) disorders are more suited for molecular augmentation. Why?

recessive because with dominant disorders, one normal allele is still present in the cells which would require precise augmentation therapy due to the gene being dosage sensitive

Why is cascade testing done?

relatives will be at a higher risk (than the general population) of being carriers in the case of a recessive disorder or chromosome translocation, or of developing disease in the case of a childhood-onset or late-onset dominant disorder

What does ex vivo gene therapy involve

removing cells from a patient, genetically modifying them in culture and returning the genetically modified autologous cells to the patient

Why does natural selection foster genetic variation in genes encoding drug handling enzymes?

the principal natural role of these enzymes is to deal with unusual exogenous chemicals (xenobiotics) in our diet and environment.

Define pharmacokinetics

the study of what the body does with, and to, the drug

Why is genetic testing for susceptibility to complex diseases of limited predictive value?

the tested susceptibility factors are of low effect

What is cascade testing

the testing of relatives after identifying a person with a pathogenic mutation

Why is tumor recurrence often a major problem?

therapeutic resistance and tumor recurrence after surgical removal

Polymorphism in _______ is a particular clinical concern when using certain immunosuppressant drugs such as 6 mercaptopurine, which is commonly used to treat childhood leukemia

thiopurine methyltransferase

What cells are targeted in somatic cell gene therapy

those directly involved in the pathogenic process

What is the purpose of target enrichment sequencing

to scan any desired subset of the genome—multiple disease genes or the whole exome—for evidence of point mutations

(tumor supressor genes/oncogenes) are recessively acting cancer genes in which the inactivation of both alleles promotes cell proliferation or inhibits apoptosis

tumor supressor genes

What is an isochromosome?

two long arms or two short arms of a particular chromosome that arises from recombination after an aberrant chromosome division.

Is transfection or viral transduction more efficient

viral transduction

____ are commonly used to get therapeutic gene constructs into cells at high efficiency, and they often allow high level expression of the therapeutic transgenes

viral vectors

What is the cause of aneuploid mosaics?

when nondisjunction or chromosome lag occurs in one of the mitotic divisions of the early embryo

Describe the total pathogenic load people are expected to inherit from their parent

- 100 mutations which is expected to result in a loss of gene function - 60 missense variants that severely damage protein structure

What are the three different broad approaches to treating genetic disorders

- Based on genetic deficiency - Based on disease phenotype due to a positively harmful effect - Those that reduce susceptibility to disease

What are the two broad ways genetic variation cause disease?

- By changing the amount of gene product made - By changing the sequence of the gene product

Describe the process of G banding

- Chromosomes treated with trypsin then stained with Giemsa - Giemsa binds to AT rich regions produced alternating light and dark regions

Describe how genotypes are multiple loci in patients are important in drug treatment

- Delivering the optimal warfarin dosage is clinically very important because there is a narrow therapeutic window. The final warfarin dose is critical, but because of genetic variation, the optimal dose varies enormously between individuals - Variations in VKORC1 and CYP2C9 remain the largest genetic determinants, accounting for about 40% of the variation in the final warfarin dose

Describe how genetic variation of the CYP2D6 enzyme affects drug metabolism

- Due to severe inactivating mutations or deletions in both CYP2D6 alleles some people have a very low activity of the enzyme and when treated with certain drugs that are normally metabolized by this enzyme alone, they fail to metabolize and excrete the drug. They are classified as poor metabolizers - people can also be classified into three additional groups: intermediate metabolizers; extensive metabolizers (with one or two activeCYP2D6 alleles); and ultrafast metabolizers. - Ultrafast metabolizers may also get little benefit from drugs that are principally metabolized by CYP2D6 (because the drug is metabolized and detoxified so quickly)

How can chromosomes with structural abnormalities result?

- Erros in recombination - Intrachromatid recombination - Somatic recombination - Incorrect joining of two broken chromosome ends - Unrepaired DNA damage - Chromatid breaks (during the G2 phase after DNA in replicated)

What rare fragile sites are located near genes and disturb their expression?

- FRAXA - FRAXE - FRA11B

Discuss two recent examples of successful in vivo gene therapy

- Hemophilia B can be treated by protein therapy using clotting factor concentrates - Type 2 Leber congenital amaurosis have been involved in injecting a recombinant AAV construct containing a trans-gene with the RPE65 coding sequence into the subretinal space allowing transduction of retinal pigment epithelial cells

The degree of the effect of replacing an amino acid with another is based on what?

- How similar the amino acids are to one another based on polarity, molecular volume, and chemical composition - The importance of the amino acid in the function of the protein - Effects on protein folding

How can somatic gene therapy modify diseased cells?

- If the problem is loss of function, a simple solution is to add functioning copies of the relevant gene - If the problem is some harmful or toxic gene product within cells. The approach might be to selectively inhibit the expression of the harmful gene product

____ of all possible base changes to the first base cause an altered interpretation for the codon.

96%

What is a synonymous/silent substitution

A change in a codon that doesn't result in a change in amino acid

What is a nonsynonymous substitution?

A change in the codon that results in a a change in amino acid

Describe the anaphase lag mechanism of producing aneuploid cells

A chromosome or chromatid is delayed in its movement during anaphase and lags behind the others, it may fail to be incorporated into one of the two daughter nuclei and is eventually degraded

Interpret the following chromsome: 46,XX,del(15)(q11q13) A cell from a female that contains a marker chromosome (an extra unidentified chromosome) A male carrier of a Robertsonian translocation that has arisen via breakpoints on the short arms of chromosomes 13 and 14 (q0 is not a chromosome band; it means the centromere). A female with an interstitial deletion on the long arm of chromosome 15 with breakpoints at q11 and q13. d) A male with a balanced reciprocal translation with breakpoints at 3q26 and 17q23.

A female with an interstitial deletion on the long arm of chromosome 15 with breakpoints at q11 and q13.

Which, if any, of the following statements is false? a) Gain-of-function mutations are often missense mutations. b) A missense mutation that has a dominant-negative effect can often produce a greater loss of protein function than a null mutation. c) Pathogenic gain-of-function and loss-of-function mutations in the same gene produce different phenotypes . d) A mutant protein that antagonizes the wild type protein produced from the normal allele is known as a hypomorph.

A mutant protein that antagonizes the wild type protein produced from the normal allele is known as a hypomorph.

Define conservative substitution

A nucleotide substitution that replaces one amino acid by another of the same chemical class.

What is a cryptic splice site

A sequence of pre mRNA that is similar to a splice site. May be due to a substitution mutation that increases the resemblance to the normal splice site

What are driver mutations

A small subset of the genetic changes that result in altered expression of genes that confer a growth advantage to their descendants

Describe what occurs during phase II of drug metabolism

A transferase adds a chemical group that facilitates excretion

What is a stop loss mutation

A type of nonsynonymous mutation where a natural stop codon is replaced a by an amino acid specifying codon.

What is a stop gain/nonsense mutation

A type of nonsynonymous mutation where an amino acid specifying codon is replaced by a premature stop codon

What is a missense mutation?

A type of nonsynonymous substitution that causes one amino acid to be replaced by another

What mutated gene is associated with colorectal cancer

APC

In cystic fibrosis, the p.Phe580del mutation leads to.... Abnormal regulation of gene expression. Aberant protein folding, leading to protein miss-folding and improper cellular localizaiton. Abnormal splicing. Protein aggregation and cell lysis.

Aberant protein folding, leading to protein miss-folding and improper cellular localizaiton.

Define aneuploidy

Abnormal number of chromosomes.

What is a constitutional chromosome abnormality?

An abnormality that is present in all nucleated cells of the body and so must have been present very early in development

Define replication slippage

An error that typically occurs in DNA replication when a single nucleotide is tandemly repeated

Define prodrug and what phase of drug metabolism does it occur in?

An inactive compound which can be converted into an active drug. Phase I

Define neomorph

An object or in this case a gene product that acquires a new function

Define hypomorph

An object or in this case gene product with a reduced ability to work normally

What are fragile sites

Areas on chromosomes that develop distinctive breaks or gaps when cells are cultured

What amino acids are in the basic group (positively charged)

Arg, Lyse, His

What amino acids are in the acid group (negative charged)?

Asp, Glu

Cancer gene therapy involves what method of somatic gene therapy? A. Modifying disease cells B. Killing disease cells C. Inhibiting disease cells

B

Which type of gene therapy is more successful? A. In vivo B. Ex vivo

B

What mutated gene is associated with melanoma

BRAF

What is an example of how a nonconservative amino acid substitution affects protein folding?

Because proline can't be accommodated into a alpha helix, a substitution with it will result in disruption of the alpha helix.

In what cells is chromothripsis most frequent?

cells with mutated p53

What is the cause of tetraploidy

failure to complete the first zygotic division: the DNA has replicated to give a content of 4C, but cell division has not then taken place as normal

Why is drug "repurposing" valuable"?

the drug has already been through lengthy and expensive clinical trials to assess its safety profile.

What are the safety concerns on gene therapy trials?

- Lack of control over vector integration - Immunogenicity of the therapeutic construct

What are three classes of nonsynonymous mutations

- Missense - Stop gain (nonsense) - Stop loss

How can synonymous/silent substitution lead to disease if it doesn't change in the amino acid sequence?

- The substitution alters RNA splicing - Mutations can occur in cis acting splice regulatory elements like enhancers, and silencer sequences.

Genetic factors are implicated in the variation between individuals in drug metabolism at what levels

- absorption - activation - target response

In what major way do tumors develop resistance to drugs?

- change conformation - amplify the gene encoding the drug target - activate an alternative pathway to bypass drug effects

What are some results of loss of function mutations

- complete absence or complete functional inactivity (a null allele) - reduced expression - an altered product with reduced functional activity

What are most genetic test designed to detect?

- detect abnormal chromosomes or pathogenic DNA variants - Consequences of genetic variants such as altered RNA/protein expression products, altered gene function, or characteristic biomarker.

What are the two broad strategies of somatic gene therapy

- disease cells are simply modified in some way so as to alleviate disease - they are selectively killed

What are some contributors to how fast a drug is metabolized?

- genes - Environment - enzymes acting on the drug

What are the four major types of neurodegenerative disorders that results from unstable CAG repeats producing an expanded polyglutamine

- spinal bulbar muscular atrophy - spinocerebellar ataxia - Huntington disease - Dentatorubropallidoluysian atrophy

Describe the mutation rates in the human genome

- the genomewide germ-line nucleotide substitution rate is 10-8 per nucleotide per generation - cytosine in CG dinucleotides is a mutational hotspot - mitochondrial genome mutation rate is many times higher than in the nuclear genome

What are some of the concerns with using viral vectors to get therapeutic gene constructs into cells?

- there has been little control over where they will insert into the genomic DNA of patient cells - They might insert by accident into an endogenous gene and block its function - They might accidentally activate an oncogene, causing tumor formation - the patient might mount a strong immune or inflammatory response

What are genetic tests used for?

- to confirm a provisional clinical diagnosis - to predict the likelihood of developing or transmitting a genetic disorder

What are some causes of a triploid embryo

- two sperm fertilizing a single egg - fertilization involving a diploid gamete

What are some examples clinically significant genetic variation in drug receptors that lead to altered responses to drugs?

- variants of beta-adrenergic receptors, cell surface receptors that have central roles in the sympathetic nervous system (ADRB1 and ADRB2) - H2RA serotonin receptor and the RYR1 ryanodine receptor

List 4 ways genetic technologies are used in the treatment of a disease

1. Production of genetically engineered vaccines 2. Genetic modification of patient or donor cells for therapy 3. Production of genetically engineered antibodies 4. Testing treatment in genetically modified animals

_____ of all possible changes to the third base cause an altered interpretation for the codon.

1/3

_____ of all possible changes to the second base cause an altered interpretation for the codon

100%

What chromosomes participate in Robertsonian translocation or centric fusion

13, 14, 15, 21, 22

Which of the following nomenclature delineates a reciprocal translocation? 45, X 46, XX,dup(1)(q22q25) 46,XX,t(2;6)(q35;p21.3) 46XY, inv(11)p11p15)

46,XX,t(2;6)(q35;p21.3)

Which of the following autosomal trisomies are not compatible with life? 13, 18, and 21 45X 46XXY 46XY+16

46XY+16

What is a premutation for fragile X syndrome

55 to close to 200 CGG repeats in the 5ʹ UTR of the FMR1 gene

How many cytochrome P450 enzymes catalyze 90% of the phase I reactions on commonly used drugs

6

T/F Identifying mutations within RNA genes is not easy and is helped by the comparing them to evolutionary conserved of many RNA genes.

F, ID is not helped by comparison to conserved genes because RNAs have intricate secondary structure through extensive intra-chain hydrogen bonding and mutations that affect secondary structure can have important consequences

T/F pathogenic mutations occur haphazardly

F, certain types of DNA sequences are more vulnerable to mutations

T/F Tetraploidy is much more common that triploidy and always compatible with life

F, it is much rarer and always lethal

T/F chromosomes lacking a centromere and having more than one centromere can successful segregate during mitosis

F, they can't and will eventually be lost.

Define base wobble

Flexibility in how the third base of a codon pairs with the 5' base of the anticodon

Which of the following is a disease whose molecular basis is an unstable expansion of short noncoding tandem repeats? Kennedy disease Huntington disease Prader-Willi syndrome Fragile X syndrome

Fragile X syndrome

What is the most commonly used method in human chromosome banding

G banding

What mutated gene is associated with lung cancer

PTEN

Are the dark bands in G banding gene rich or poor? Why?

Gene poor because the stains binds to the AT regions and genes are found in the GC regions

What types of genes are prone to intragenic deletions?

Genes that have multiple large introns (which usually contain diverse types of repeats)

What is the main cause of the difference in performance of small molecule drugs between people

Genetic variation

What type of stain is traditionally used to visualize metaphase chromosomes in preparing a karyotype? Silver Coomassie Giemsa Xylene cyanol

Giemsa

What are the consequences of defective mismatch repair?

Global DNA instability in which replication errors in newly synthesized DNA go uncorrected.

What amino acids are non polar

Gly, Ala, VAl, Leu, Pro, Met, Phe, Trp

Which, if any, of the following statements is true? a) Autologous cell transplantation is involved in in vivo gene therapies: cells from an individual are genetically modified and then returned to that individual. b) Adenovirus vectors have the advantage that they offer very high level expression and are well suited to gene therapy for blood disorders. c) Adenovirus vectors have a better safety profile than adeno-associated virus vectors and have a larger insert size capacity. d) Adeno-associated virus vectors are well suited to gene therapy for blood disorders but have a low insert size capacity

None all are false Autologous cell transplantation is involved in ex vivo gene therapy. Both adenovirus vectors and adeno-associated virus vectors are not well suited to gene therapy for blood disorders because neither of them are integrating vectors (because blood cells have short lives some kind of retroviral integrating vectors are needed for gene therapy for blood disorders - the hope is to insert the gene constructs into the chromosomal DNA of hematopoietic stem cells). Adenovirus vectors have a poor safety record because they often induce powerful inflammatory responses in the recipient of therapy.

With regard to drug metabolism, which, if any, of the following statements, is true? a) The therapeutic window is simply the range of plasma drug concentrations in which the drug has therapeutic benefit. b) Each individual drug molecule is metabolized by a specific drug-metabolizing enzyme that is dedicated to the metabolism of that drug. c) An ultrafast metabolizer is a person who metabolizes a drug too quickly and so is at risk of an overdose d) A poor metabolizer is a person who cannot metabolize a drug properly and is at risk of anunderdose.

None. All are false. a) The therapeutic window is the range of plasma drug concentrations in which the drug has therapeutic benefit without causing extra safety risks due to drug toxicity. b) Individual drug molecules can sometimes be metabolized by one of several drugmetabolizing enzymes, and many drug-metabolizing enzymes metabolize multiple different drugs. c) An ultrafast metabolizer is a person who metabolizes a drug too quickly and so is at risk of an underdose. d) A poor metabolizer is a person who cannot metabolize a drug properly and is at risk of an overdose.

What type of point mutations are easier to see?

Nonsense, insertions/deletions that change the reading frame

What is a potential risk of gene-silencing therapy using RNA interference?

Off-target gene sequences getting silenced

What is a gain of function mutation?

One that has a phenotypic effect in the presence of a normal allele that cannot be compensated for by producing more of the normal gene product

What is a somatic/acquired chromosome abnormality?

One that is present in only certain cells or tissues of a person

Describe what occurs during phase I of drug metabolism

Oxidation reactions as a result of monooxgenases that produce a polar drug derivative with a reactive group. Prodrugs can be created

A nonsense mutation would be expected to result in ..... Production of a polypeptide shorter than normally expected Production of a gene product with a amino acid substitution No change in the encoded polypeptide Alter the regulation of gene expression of the encoded polypeptide.

Production of a polypeptide shorter than normally expected

What is the most actively used method for treating disease by gene silencing therapy?

RNA interference

Which of the following is a disease whose molecular basis is caused by a gene-pseudo gene sequence exchange? Steroid 21-hydroxylase deficiency Hemophilia A Sickle cell animia Amyotrophic lateral sclerosis

Steroid 21-hydroxylase deficiency

What are derivative chromosomes

Structurally rearranged chromosomes that acquired a centromere when they previously didn't have one and are now able to stably participate in mitosis

Define pharmacogenetics

Study of the interrelationship of genetic differences and drug effects

T/F Driver mutations result in altered expression of genes that confer a growth advantage to their descendants.

T

T/F Germ-line gene therapy that involves modifying nuclear DNA is widely banned in humans for ethical reasons

T

T/F Loss-of-function and gain-of-function mutations in the same gene can result in different phenotypes.

T

T/F conservative substitutions often has minimal consequences for how the protein functions

T

T/F drug response phenotypes can be multifactorial

T

T/F genetic variation between individuals has an important influence on both the efficacy and the safety of drugs

T

T/F most pathogenic mutations affect individual genes

T

T/F point mutations could be significant contributors to complex common diseases by causing important changes in gene expression

T

T/F point mutations in noncoding DNA might make a very small contribution to monogenic disorders

T

T/F Individuals with very high repeat numbers are more severely affected and develop symptoms at an earlier age than those individuals who have a number of repeats that falls at the lower end of the disease range

T Because the mutation is dynamic, transmission down successive generations in a family can lead to mutant alleles with an increasing repeat number and increasing disease severity in successive generations

T/F triploids very seldom survive to term, and the condition is not compatible with life

T, due to an imbalance between products encoded on the X chromosome and autosomes, for which X-chromosome inactivation would be unable to compensate

What mutated gene is associated with breast cancer

TP53

What mutated gene is associated with ovarian cancer

TP53

Regarding mutations, which of the following statements, if any, is false? a) A de novo mutation is one that has occurred post-zygotically. b) Each of us has multiple genes where both the maternal and paternal alleles have inactivating mutations. c) The vast majority of mutations in our DNA do not adversely affect gene expression. d) The mitochondrial genome has a very high gene density and accordingly the mutation frequency in mtDNA is low

a) A de novo mutation is one that has occurred post-zygotically. d) The mitochondrial genome has a very high gene density and accordingly the mutation frequency in mtDNA is low. (De novo mutations can occur at any stage, including within the zygote. Mutation frequency has nothing to do with gene density and the frequency of mutations in mtDNA exceeds that of mutations in nuclear DNA by a factor of about 10 or more.)

Concerning the efficacy of small molecule drugs, which, if any, of the following statements is true? a) At the level of clinical trials drugs can vary widely in how effective they are. b) Once a drug has received regulatory approval, we can be sure that it will be effective in all patients, although some people will receive more benefit from it than others. c) Drugs used to treat psychiatric disorders are particularly effective. d) Stains and beta blockers that were meant to reduce the risk of heart disease are goodexamples of drugs that are largely ineffective.

a) At the level of clinical trials drugs can vary widely in how effective they are

Which, if any, of the following statements is false? a) Chromothripsis is an extraordinary event in which multiple chromosomes within a cell are shattered into many pieces. b) Chromothripsis is much more like to occur in cells where the TP53 gene has received loss-of-function mutations. c) Kataegis is a type of somatic hypermutation. d) The mutations involved in a kataegis event are clustered in one subchromosomal region.

a) Chromothripsis is an extraordinary event in which multiple chromosomes within a cell are shattered into many pieces. (Chromothripis is a localized event. Shattering of multiple chromosomes would leave a cell so adversely affected that it could not be expected to function normally, or even survive)

With regard to treatment of inborn errors of metabolism (IEM), which of the following statements, if any, is false? a) IEMs are all single gene disorders that have been studied for many decades, leading to the development of successful treatment in all cases. b) IEMs can be treated by augmentation therapy, treatment to inhibit positively harmful effects, or by prevention therapy. c) Treatment for some individual IEMs can involve both augmentation therapy plus treatment to inhibit positively harmful effects. d) Treatment of some IEMs involves artificially forcing an increase in a minor metabolic pathway to counteract a build-up in a toxic metabolite produced by a metabolic block in a major metabolic pathway.

a) IEMs are all single gene disorders that have been studied for many decades, leading to the development of successful treatment in all cases. (For some IEMs there remains no suitable treatment.)

Concerning prenatal diagnosis, which, if any, of the following statements is false? a) It relies on surgical procedures to recover fetal tissues from a pregnant woman. b) Chorion villus biopsies are typically taken around 16 weeks of gestation. c) Amniotic fluid samples allow culturing of fetal cells for cytogenetic analyses as well as allowing DNA analyses. d) There is always a small excess risk of miscarriage.

a) It relies on surgical procedures to recover fetal tissues from a pregnant woman. b) Chorion villus biopsies are typically taken around 16 weeks of gestation. d) There is always a small excess risk of miscarriage. (Noninvasive techniques that do not involve surgery (and the associated excess risk of miscarriage) are increasingly being adopted. Instead of analysing fetal cells samples of maternal plasma are analysed (they contain small amounts of fetal DNA from fetal cells that had undergone apoptosis). Chorion villus biopsies are typically carried out in the first trimester. )

What is meant by genetic screening?

carrying out proactive assays to identify individuals in communities and populations at increased risk of carrying abnormal chromosomes or harmful genetic variants

Which, if any, of the following statements is incorrect or very likely to be incorrect? a) Epigenetic dysregulation is essentially a universal feature of tumors. b) Epigenetic dysregulation in cancer cells always arises as a result of mutation at a chromatin modifier locus. c) There is an overall increase in DNA methylation across the genome of cancer cells but with local DNA hypomethylation at the promoters of a few hundred genes. d) Epigenetic dysregulation may sometimes initiate tumorigenesis.

b) Epigenetic dysregulation in cancer cells always arises as a result of mutation at a chromatin modifier locus. c) There is an overall increase in DNA methylation across the genome of cancer cells but with local DNA hypomethylation at the promoters of a few hundred genes. In addition to mutation at a chromatin modifier locus, increasing evidence supports epigenetic dysregulation as an occasional initiator of tumorigenesis. ) There is an overall reduction in DNA methylation across the genome of cancer cells but with local DNA hypermethylation at the promoters of a few hundred genes.

Concerning gene transfer into human cells, which, if any, of the following statements is false? a) Integrating viruses can insert genes into the chromosomes of a host cell. b) Most integrating viruses insert their DNA into a specific location within the genome. c) The great value of integrating viruses is that they allow foreign (and therefore, therapeutic) DNA to be stably inherited so that it passes to all descendant cells of the transduced cell. d) Because non-integrating viruses cannot insert their DNA into the chromosomes of a cell, the transduced DNA is quickly destroyed by enzymes within the host cell.

b) Most integrating viruses insert their DNA into a specific location within the genome. d) Because non-integrating viruses cannot insert their DNA into the chromosomes of a cell, the transduced DNA is quickly destroyed by enzymes within the host cell.

Concerning making animal models of human disease, which, if any, of the following statements is false? a) Pronuclear microinjection is a general way of making a transgenic animal and involves microinjection of foreign DNA into a fertilized egg cell. b) Pronuclear microinjection is best suited to modelling recessively inherited single gene disorders. c) Gene targeting using embryonic stem cells depends on having well-characterized embryonic stem cell lines that can readily allow transmission through the germ line. d) Gene targeting using embryonic stem cells in mice is a popular way of modelling disease phenotypes that result from a gain-of-function.

b) Pronuclear microinjection is best suited to modelling recessively inherited single gene disorders. d) Gene targeting using embryonic stem cells in mice is a popular way of modelling disease phenotypes that result from a gain-of-function. (Pronuclear microinjection is not suited to modelling recessively inherited single gene disorders, but has often been used to model disease phenotypes that result from a gain-of-function. Gene targeting using embryonic stem cells in mice is not well suited to modelling disease phenotypes that result from a gain-of-function but is a popular way of modelling the loss-of-function in recessively inherited single gene disorders.)

Concerning animal models of human disease, which, if any, of the following statements is false? a) Primates should be the best animal models, but for mostly practical reasons, rodent models have been preferred. b) Rats have been the preferred disease models because they offer the best balance between rapid breeding, size and the cost of maintaining colonies. c) Rodent models are especially suited to modelling neuropsychiatric disorders. d) All animal models have limitations regarding how far we can make inferences to help understand human disease.

b) Rats have been the preferred disease models because they offer the best balance between rapid breeding, size and the cost of maintaining colonies. c) Rodent models are especially suited to modelling neuropsychiatric disorders. Mice have been the preferred disease models, but rodent models are poorly suited to modelling neuropsychiatric disorders (in part, because they are not good models of cognitive capacity).

Which, if any, of the following statements is false? a) Conventional chromosome banding analyses are often very difficult to carry out in the case of solid tumor samples. b) Spectral karyotyping simply means standard chromosome FISH that is applied to tumor cells. c) Genomewide analyses can be carried out by microarray hybridization to look for evidence of many types of chromosome abnormalities in solid tumors. d) Genomewide analyses cannot be carried out by chromosome FISH analyses on cancer cells

b) Spectral karyotyping simply means standard chromosome FISH that is applied to tumor cells. d) Genomewide analyses cannot be carried out by chromosome FISH analyses on cancer cells. (Spectral karyotyping (SKY) is an exceptional type of multicolour chromosome FISH in which genomewide analyses are carried out to get a detailed representation of all chromosomes in cancer cells)

Concerning preimplantation genetic diagnosis, which, if any, of the following statements is incorrect? a) It is carried out within the context of assisted reproduction. b) The analyses always involve genotyping just a single cell and so are technically difficult. c) Sometime a single blastomere is analysed from the embryo. d) Sometimes a polar body is analysed to infer the genotype of the embryo.

b) The analyses always involve genotyping just a single cell and so are technically difficult. d) Sometimes a polar body is analysed to infer the genotype of the embryo. (Quite often the embryo is cultured to the late blastocyst stage and a few cells are taken for analysis from the trophectoderm (which will give rise to extra-embryonic membranes). The analyses are still technically difficult, but less so than when trying to analyze a single blastomere. A polar body is a cell formed by one of the two asymmetric cell divisions in female meiosis and can be used to infer the genotype of the oocyte (when there is a risk of a maternal transmission of a harmful genetic variant).)

Which, if any, of the following statements is true? a) A person is said to be a chimera if he or she has two or more genetically different cells. b) The diversity of immunoglobulins made by a person is due to genetic mosaicism. c) Having cells that inactivate the paternal X and cells that inactivate the maternal X is an example of genetic mosaicism in female mammals. d) A person with cell populations that are genetically different because they originated from two different zygotes is described as a genetic mosaic.

b) The diversity of immunoglobulins made by a person is due to genetic mosaicism. (*a) This person would be described as a genetic mosaic. c) X-inactivation is an epigenetic phenomenon and so it would be difficult to describe the cellular mosaicism as an example of genetic mosaicism. d) This person would be described as a chimera*)

Which, if any, of the following statements is false? a) The great majority of clinical gene therapy trials have had limited success b) The only successful gene therapies have been for recessive blood disorders. c) The only successful gene therapies have been ex vivo gene therapies. d) Gene therapy for inherited disorders represents a minority of clinical gene therapy trials.

b) The only successful gene therapies have been for recessive blood disorders. c) The only successful gene therapies have been ex vivo gene therapies. (There have been examples of other successful gene therapies that involve brain disorders and in vivo gene therapy for eye disorders, for example. )

Concerning disorders resulting from unstable expansion of tandem oligonucleotide repeats, which, if any of the following statements is false. a) The expansions can occur in coding DNA in some cases, and in noncoding DNA in other cases. b) The repeats are of a variable number of nucleotides (from three to six) in both coding DNA and noncoding DNA. c) The expansions in noncoding DNA are generally much larger in size than those in coding DNA. d) The expanded arrays in noncoding DNA always result in loss of function of the host gene or of a neighboring gene.

b) The repeats are of a variable number of nucleotides (from three to six) in both coding DNA and noncoding DNA. d) The expanded arrays in noncoding DNA always result in loss of function of the host gene or of a neighboring gene.

Which, if any, of the following statements is false? a) Genome editing means making a predetermined change to the nucleotide sequence at just one locus within an intact cell. b) The specificity of genome editing depends on an initial site-specific cleavage of doublestranded DNA following base pairing with specifically designed nucleotide sequences. c) Genome editing has the potential to permit specific "gene correction" in which a mutant sequence in a cell is restored to the normal sequence. d) Genome editing might also have therapeutic potential by specifically inactivating a gene in some cases.

b) The specificity of genome editing depends on an initial site-specific cleavage of doublestranded DNA following base pairing with specifically designed nucleotide sequences. (The site-specific cleavage is also often carried out following recognition of the sequence at the target locus by a combination of zinc fingers within zinc finger nuclease proteins.)

Which, if any, of the following descriptions is false? a) Zinc fingers are elements of protein secondary structure in which the polypeptide chain folds back upon itself after co-ordination of a Zn2+ ion with selected amino acids, often a pair of cysteines and a pair of histidines. b) Zinc finger nucleases are natural proteins containing a sequence of zinc fingers that can bind to specific sequences in DNA. c) After zinc finger nucleases bind to both DNA strands at a specific DNA sequence they attract cellular DNA cleavage enzymes, inducing them to make a double-stranded break at just that one position in the genome. d) The CRISPR-Cas system also allows genome editing but in this case the target DNA sequences are recognized by guide RNA sequences rather than proteins.

b) Zinc finger nucleases are natural proteins containing a sequence of zinc fingers that can bind to specific sequences in DNA. c) After zinc finger nucleases bind to both DNA strands at a specific DNA sequence they attract cellular DNA cleavage enzymes, inducing them to make a double stranded break at just that one position in the genome. (Zinc finger nucleases are not natural: they are proteins produced after genetic engineering to covalently join DNA sequences that can specify a series of zinc finger modules to a bacterial DNA sequence that can specify a DNA cleavage domain.)

Which, if any, of the following statements is false? a) p53 acts as a brake on cell growth but stimulates apoptotic pathways. b) apoptosis occurs only after a death signal is received by one cell from another cell. c) the death signal starts a pathway that culminates in the activation of a class of proteolytic enzymes called caspases. d) caspases attack cellular proteins and release an endonuclease that cleaves the cellular NA into small fragments.

b) apoptosis occurs only after a death signal is received by one cell from another cell. There are also intrinsic apoptosis pathways that respond to internal cellular damage that can be caused by reactive oxygen species, ionizing radiation and so on.

Which, if any, of the following statements is false? a) p53 acts as a brake on the cell cycle. b) p53 and RB1 are mutually antagonistic. c) p53 is normally inhibited by being bound to the MDM2 protein, but when phosphorylated, it changes conformation and is released from MDM2. d) At high concentrations p53 stimulates the transcription of various genes that inhibit apoptosis.

b) p53 and RB1 are mutually antagonistic. d) At high concentrations p53 stimulates the transcription of various genes that inhibit apoptosis.

Which of the following statements, if any, is false? a) Monoclonal antibodies are made by identical immune cells and so will recognize and bind just one specific epitope on a target molecule. b) Monoclonal antibodies of rodent origin are far from ideal therapeutic agents because of their short half-life in human serum and the potential for immune responses by the recipient. c) Humanized antibodies are hybrid antibodies that have constant regions of human origin but variable regions of rodent origin. d) An intrabody is an artificial constructs with just a single chain that is linked to variable domains and, unlike regular antibodies with four polypeptide chains, has the potential to work inside cells.

c) Humanized antibodies are hybrid antibodies that have constant regions of human origin but variable regions of rodent origin. The variable domains in humanized antibodies are of human origin, except for the complementarity-determining regions, which are of rodent origin.

Concerning genetic screening, which, if any, of the following statements is false? a) Genetic screening is carried out primarily in communities and populations b) In carrier screening the motivation is to identify carriers of a mutant allele for a severe autosomal recessive disorder that has a high prevalence in the community or population. c) In most cases of pregnancy screening the motivation is to identify whether a fetus carries a genetic variant associated with a harmful single gene disorder. d) In newborn screening the motivation is often to target early treatment for serious disorders for which early intervention can make a significant difference.

c) In most cases of pregnancy screening the motivation is to identify whether a fetus carries a genetic variant associated with a harmful single gene disorder (In most cases of pregnancy screening the motivation is to identify maternal age-dependent aneuploidy in the fetus, notably trisomy 21.)

Which, if any, of the following statements is false? a) Mismatch repair is dedicated to repairing errors made during DNA replication. b) MutSα is responsible for recognizing single base mismatches during DNA replication. c) MutSβ is responsible for recognizing all short insertion and deletion errors made during DNA replication. d) MutLα contributes an endonuclease activity that is required to nick the DNA during DNA repair.

c) MutSβ is responsible for recognizing all short insertion and deletion errors made during DNA replication. (MutSα recognizes single nucleotide insertions/deletions as well as single base mismatches while MutSβ recognizes longer insertion/deletion errors that arise from replication slippage. )

Which, if any, of the following statements is false? a) Hematopoietic stem cells are multipotent because they can give rise to a variety of different cell types. b) Mammalian embryonic stem cell lines are pluripotent because they can give rise to all types of cell in the body. c) Transdifferentiation is a type of epigenetic reprogramming in which a differentiated cell is induced to become pluripotent. d) A transit amplifying cell is a cell produced b asymmetric division of a stem cell and has the potential to give rise to differentiated cells.

c) Transdifferentiation is a type of epigenetic reprogramming in which a differentiated cell is induced to become pluripotent.

What type of cancer is associated with defective mismatch repair

colon cancer because MMR deficiency sabotages a key defense system that protects against colorectal cell proliferation

Define euploidy

correct number of chromosomes

Which, if any, of the following statements is false? a) Transdifferentiation means reprogramming of a differentiated cell so that it acquires the characteristics of another type of differentiated cell. b) In dedifferentiation a differentiated cell is artificially reprogrammed so that it behaves as a pluripotent cell. c) Human induced pluripotent stem (iPS) cell lines are usually generated by artificial dedifferentiation of readily accessible human cells, such as skin cells. d) Human iPS cell technologies do not offer clinical applications but they are of value for studying pathways of cellular differentiation

d) Human iPS cell technologies do not offer clinical applications but they are of value for studying pathways of cellular differentiation (Human iPS cell technologies have the potential for valuable clinical applications, most readily in creating cellular disease models and possibly in extending ex vivo gene therapy.)

Which, if any, of the following statements is false? a) RNA interference (RNAi) is a cellular defense mechanism that is triggered by the presence in cells of unnatural double-stranded RNA, as can occur after viral infections. b) RNAi therapy is a type of RNA-targeted therapy in which specific double-stranded RNA constructs are engineered to appear in diseased cells in order to incite the cells to destroy any RNA that contains the same sequence. c) By destroying RNAs that are related to a specifically introduced genetic construct, artificial RNAi is effectively a type of gene-specific silencing. d) RNAi therapy is best suited to silencing genes so as to replicate a phenotype caused by loss-of-function mutations.

d) RNAi therapy is best suited to silencing genes so as to replicate a phenotype caused by loss-of-function mutations. (RNAi is a convenient way of silencing a gene in cultured cells as a way of understanding its function but RNAi therapy is better suited to specific silencing of a positively harmful gene in diseased cells than it is to replicating loss-of-function phenotypes.)

Which, if any, of the following statements is false? a) A null allele is one where the gene has been deleted or received an inactivating mutation causing complete loss of gene function. b) Inactivating point mutations are a common cause of pathogenesis in recessively inherited disorders. c) Inactivating point mutations are a common cause of pathogenesis in dominantly inherited disorders. d) When a gain-of-function allele is known to be pathogenic in a single gene disorder, a heterozygote will always show disease symptoms.

d) When a gain-of-function allele is known to be pathogenic in a single gene disorder, a heterozygote will always show disease symptoms. (It depends on the penetrance. In some cases there is a late age at onset of symptoms and so a person may appear perfectly healthy. c) many dominant disorders are due to haploinsufficency where one allele is a loss-of-function allele that is often an inactivating point mutation. )

Why is telomere shortening an important factor in cancer? a. It is advantageous for cancer cells because it makes rapid cell division easier b. It leads to aneuploidy, which causes cancer c. It makes rapid cell division more difficult by requiring a DNA break repair before division can continue d. It leads to the expression of telomerase in cancer cells

d. It leads to the expression of telomerase in cancer cells

In (direct/hairpin) siRNA therapy, long double-stranded RNA is used in mammalian cell culture thats results in the indiscriminate destruction of mRNAs.

direct

What type of disorders has ex vivo gene therapy been used to treat?

disorders by genetic modification of impure populations of hematopoietic stem cells that give rise to blood cells or some types of tissue immune system cell

Oncogenes act in a ___________ manner while tumor suppressor genes act in a ___________ manner.

dominant; recessive

A silent mutation.... is a mutation which lead to silencing of the gene expression of the encoded polypeptide results in a mutated coded that specifies the same amino acid as the original codon. results in a mutated coded is different than the same amino acid as the original codon. is the result of a conservative mutation that does not lead to a change in the amino acid in the encoded polypeptide, but the changes is such that it does not lead to a functional change in the encoded protein

results in a mutated coded that specifies the same amino acid as the original codon.

How are noninvasive prenatal testing done?

samples of freely circulating DNA recovered from maternal plasma are analyzed massively parallel DNA sequencing to infer fetal DNA variants and the fetal genome sequence

An assay has a high (specificity/sensitivity) when a high proportion of all people with the condition are correctly identified as such

sensitivity

(Somatic/germ line) therapy seeks to modify specific cells or tissues of the patient in a way that is confined to that patient

somatic

A person with what type of chromosome abnormality is considered a genetic mosaic?

somatic/acquired

An assay has a high (specificity/sensitivity) when a high proportion of all people who do not have the condition are correctly identified as such

specificity

What is chromosomal microarray analysis

the clinical application of microarray-based DNA hybridization assays to scan the DNA of each chromosome for changes in copy number (deletions or duplications) of DNA segments from tens of kilobases to tens of megabases