genetics

hich of the following statements about differentiation is true? A. Differentiation occurs both in embryos and adults and involves alterations in gene expression that result from dynamic changes in transcription factor complements as cells mature. B. Differentiation happens only at embryonic stages and involves temporally predictable alterations in gene expression. C. Differentiation is limited to cell lineages that develop from long-term stem cells (like blood or skin) and involves a terminal state of maturation in which gene expression ceases because the cell dies or the nucleus is lost. D. Differentiation is primarily a mechanism for tumor suppression and acts in parallel to the classical P53 / Retinoblastoma pathway, except in elephants which have extra copies of the P53 gene, TP53. E. Differentiation inevitably alters the number of genes within the genome, and so irreversibly limits the potential of cells to develop along other pathways.

A

A complementation test is often used as a first step in determining whether A. two mutant alleles are identical to one another B. two mutants affect the same gene C. a chromosomal inversion is present D. one mutant can be rescued by a different allele at the same locus E. a mutant individual's vanity can get the best of it

B

Studies of several model organisms suggest that if a mutation has an observable effect at all, it could reasonably be expected to influence A. all traits B. at least 5 traits C. 30% of traits D. 30-45 traits E. more than 50 traits

B

Studies of human genome variation have indicated that: A. Homozygous loss of function mutations are invariably lethal. B. Icelanders are more prone to mutation than other populations. C. Individuals are often heterozygous or homozygous for loss of function mutations. D. Loss of function alleles are derived invariably from paternal genomes. E. Most loss of function mutations are X-linked.

C

Synteny refers to: A. translocations that often occur between chromosomes during evolution B. consequences of inversion for meiotic synapse formation C. gene order that is shared on chromosomal regions of different species D. fusions that sometimes arise evolutionarily between non-homologous chromosomes E. synapses that can occur between non-homologous chromosomes during DNA repair

C

CRISPR/Cas9 knockouts often yield small deletions or insertions because A. Homologous recombination is imprecise B. Cas9 acts as a restriction endonuclease C. Two guide RNAs are required for Cas9 targeting D. Cas9 preferntially targets trinucleotide repeats E. Double strand breaks are repaired by non-homologous end-joining

E

Since the inception of DNA sequencing, the amount of raw sequence data that can be generated by a sequencing instrument per "run" has increased by: A. less than 2-fold B. less than 20-fold C. less than 200-fold D. less than 2000-fold E. none of the above

E

The eukaryotic Pre-Replication Complex comprises several factors including: A. origin recognition complex (ORC) proteins B. proliferating cell nuclear antigen (PCNA) C. RNA polymerase II (RNA pol II) D. DNA methyltransferase (DNMT) E. all of the above

A

Dapi is an example of: A. a plant defense chemical B. a chemical used to visualize protein by fluorescence C. a DNA minor groove intercalator D. both A and B E. both A and C

C

In trying to understand the buffering of phenotypes against genetic and environmental perturbation, embryologist Conrad Waddington envisaged an "epigenetic landscape" in which an embryo, represented as a ball, rolls downhill through certain valleys but not others, with minor deviations not affecting the normal path. In Waddington's imagery, the surface of this landscape was dictated by underlying: A. histone modifications B. transcription factors and cofactors C. genes and their interactions D. environmental conditions E. DNA methylases

C

Which of the following are mechanisms known to regulate the function of transcription factors? A. phosphorylation B. conformational change C. acetylation D. both a and b E. both a and c

D

Humans have remarkably high rates of aneuploidy that can lead to developmental abnormalities causing spontaneous abortions or severe congenital defects at birth. The likelihood of aneuploidy increases with: A. the longer it takes to complete meiosis B. the smaller the size of the chromosome being considered C. the faster the rate of DNA replication D. increased CENP-A synthesis in younger individuals

A

In Fred Griffith's classic study of S and R form Streptococcus pneumoniae, he found that: A. S form could arise from R form if material was provided from killed S form B. transfer of genetic information could occur both in the mouse (in vivo) and in a test tube (in vitro) C. genetic information depended on conjugation between live R and S form bacteria D. R form spontaneously reverted to S form that had lost its virulence E. transformation with purified RNA was sufficient to convert R form to S form

A

Many events in animal development involve genes that function in just a few major signaling pathways (Wnt, Hedgehog, RTK, Notch, BMP). Several of these genes and pathways were first identified through analyses of Drosophila mutants and only later shown to be present, and functioning similarly, in vertebrates. One example is hedgehog (hh; named after the first instar larva phenotype of extra bristles). When a similar gene was found in vertebrates it was named Sonic hedgehog (Shh; yes, after a cartoon character) and later, when another similar gene was found in vertebrates, it was named Indian hedgehog (Ihh; after an actual hedgehog). Based on your knowledge of genome evolution, which statement likely best describes the evolutionary relationships of these genes? A. all are homologues of one another, Shh and Ihh are ancient ohnologs of each another, and hh is orthologous to both Shh and Ihh B. all are paralogues of one another, Shh and Ihh are ancient orthologues of each other, and hh is paralogous to both Shh and Ihh C. all are orthologues of one another, Shh and Ihh are ancient homologues of each another, and hh is orthologous to both Shh and Ihh D. all are homologues of one another, hh and Shh are ohnologs of one another whereas hh and Ihh are paralogues of one another E. all are ohnologs of one another, hh and Shh are paralogues of one another whereas hh and Ihh are paralogues of one another

A

Mathematical analyses of linear genetic pathways suggest that hypomorphic alleles are more likely to be recessive if: A. there are more genes in the pathway B. mutations are in coding sequence C. the pathway consists of two genes, with no epistasis between them D. all genes are physically linked E. the genes encode transcription factors rather than enzymes

A

Red-green colorblindness occurs frequently in human males because: A. heteroduplexes can form between nearly identical sequences in different genes B. opsin genes are prone to mutations that generate premature stop codons C. gene duplications often cause sensory defects D. new genes are especially unstable E. X-chromosome inactivation makes males unusually susceptible to new mutations in X chromosome genes

A

Sets of phenotypic traits are sometimes considered to be modular because: A. Genetic and cellular interactions within sets of traits are stronger and more frequent than between sets of traits. B. Genes normally have weak pleiotropic effects within sets of traits but stronger effect between sets of traits. C. Environmental factors rarely effect more than one trait. D. All of the above. E. None of the above.

A

Spectral karyotyping is especially useful for identifying: A. chromosomal fusions, inversions, and aneuploidies B. nucleotide changes causing non-disjunction C. meiotic cross-over products in genetic mapping D. molecular mechanisms of radiation resistance E. new mutations induced by alkylating agents like ENU or EMS

A

The Retinoblastoma protein (Rb) is sometimes referred to as "tumor suppressor" because: A. Rb inactivation leads to unrestrained E2F activity and cell cycle progression B. phosphorylation of Rb typically suppresses tumor formation C. Rb interferes with CDK2/CyclinE and CDK4/CyclinD functions, preventing these complexes from inhibiting E2F activity D. injection of Rb into the retina leads to spontaneous tumor regression E. Rb-dependent proofreading of DNA allows replication errors to be corrected

A

Which of the following is NOT true about meiosis? A. sister chromatids exchange segmens by crossing over in prophase I B. homologous chromosomes synapse with one another C. sister centromeres detach from each other in anaphase II D. the cytoplasm divides to form four haploid cells E. crossing over occurs between non-sister chromatids in prophase I

A

"Genetic distance" refers to: A. the number of base pairs between any two locations in the genome B. the frequency of recombination between any two locations in the genome C. the physical space between sister chromatids as determined by CENP-A and cohesin D. the difference in telomere length between early and later life E. none of the above

B

A mature mRNA includes the following sequence: 5'-UAC-GUA-CGG-3'. What was the template strand sequence in DNA from which it was transcribed? A. 3'-CCG-TAC-GTA-3' B. 5'-CCG-TAC-GTA-3' C. 5'-TAC-GTA-CGG-3' D. 3'-TAC-GTA-CGG-5'

B

Alleles are considered to have additive effects when... A. each copy adds precisely one unit of a value to trait expression B. each copy has a discernible effect on the phenotype that is distinguishable from other alleles at the same locus C. epistasis is only unidirectional D. similar alleles at other loci can compensate, leading to redundancy E. only discrete phenotypes are present

B

An important function of serine/arginine-rich (SR) proteins is to: A. bind DNA to prevent splicing at adjacent sites B. bind RNA to prevent splicing at adjacent sites C. bind polyA tails to promote ribosome dissociation D. bind histone-3 tails to methylate CpG islands E. bind premature termination codons to target defective mRNAs for degradation

B

For an mRNA transcribed from a single-exon gene, a premature stop codon would most likely result in: A. nonstop decay B. a shorter protein C. mis-splicing D. degradation by nuclear TRAMP complex E. lack of 40S scanning

B

For genetic mapping, production of a 100-individual family using a backcross design (heterozygous F1 to homozygous mutant parent) rather than an in-cross design (heterozygous F1 to heterozygous F1) would be expected to: A. halve the number of potentially informative meioses to 50 B. halve the number of potentially informative meiosis to 100 C. double the number of potentially informative meioses to 200 D. increase the mapping resolution by 50% E. increase the mapping resolution by 100%

B

Gene bodies sometimes overlap because A. cis-regulatory elements can be far from the coding sequence itself B. exons and introns can be read from different strands of DNA C. transposable elements normally copy gene coding sequences "in frame" D. genes frequently share a core promoter E. alternative splicing allows single primary transcripts to encode >1 polypeptide from >1 gene

B

Imagine you are studying the development of sea cucumbers, the cells of which are predominantly 2N. You find that the typical skin gland cell is 48N and has a single large nucleus, whereas most epidermal cells are 4N with two nuclei. What might you infer about cycling of these cells? A. gland cells lack an S phase, whereas epidermal cells lack an M phase B. gland cells lack an M phase, whereas epidermal cells have an abbreviated M phase C. gland cells have an extended M phase, whereas epidermal cells have an abbreviated S phase D. gland cells have an extended G2 phase, whereas epidermal cells have an abbreviated G1 phase E. gland cells lack G1 and S phases, whereas epidermal cells lack G2 and M phases

B

In a human pedigree for a family segregating a gain-of-function allele of FGFR1, you might expect that "filled" circles (females) or squares (males) represent individuals who are: A. homozygous for the mutant allele B. heterozygous for the mutant allele C. recessive D. unaffected phenotypically E. dead

B

Oxidation of nucleotide bases can result in the conversion of a G to an oxidized variant ("GO"). In the absence of base or nucleotide excision repair, or mismatch repair, this damage could ultimately result in: E a T to A transition mutation A. a G to C transition mutation B. a G to T transversion mutation C. a C to G transversion mutation D. a GO to G revertant mutation

B

Replication in eukaryotic cells involves: A. repeated use of a single origin per chromosome arm B. selection of multiple origins from sites licensed by the Pre-Replication Complex C. activation of condensins to disrupt nucleosomes downstream of the replication fork D. shelterin binding to the kinetochore E. none of the above

B

Studies of the gene regulatory network of sea urchin micromere and skeletal development showed that transcription factor Pmar1 is genetically upstream of transcription factor HesC in a double negative gate, and that injection of Pmar1 mRNA results in the formation of too many micromeres. Given your knowledge of gene regulatory logic, how could you potentially rescue a normal number of micromeres in embryos injected with Pmar1 mRNA? A. by co-injecting mRNA for membrane-tethered form of beta-catenin B. by co-injecting mRNA for HesC C. by co-injecting Otx protein D. by co-injecting mRNA for Sm27 E. by co-injecting Cas9 and guide RNA targeting the SoxC gene

B

The stop codon of a typical eukaryotic protein-coding gene marks... A. the place where transcription starts B. the final codon before an untranslated region C. the place where transcription ends D. the end of the gene E. the final frameshift in the coding sequence

B

Transcriptional adaptation refers to: A. the observation that gene expression often changes as cell types differentiate during development B. the phenomenon in which non-sense mediated decay of transcripts produced by one gene can induce higher levels of expression from functionally similar genes C. the mechanism by which RNA perdurance in the cytoplasm of cells is controlled with exonucleases that attack polyA tails of mature mRNAs D. short-term physiological regulation of gene expression in response to environmental conditions E. the finding that genes located within chromosomal inversions can acquire mutations allowing them to function together as a "supergene" in determining individual phenotypes

B

Trinucleotide repeat expansion resulting in excess glutamine residues and toxicity of the translated protein underlies which condition? A. Turner syndrome B. Huntington disease C. Telomere maintenance disorder D. Roberts syndrome E. Zika infection

B

When seeking to meiotically map a new mutant, it is often valuable to have a large mapping cross principally because having more individuals... A. will reveal the causative mutation by any of several different genotyping methods B. allows more sampling of cross-overs and a narrower critical interval if marker locus densities are great enough C. helps to ensure that phenotypes are genetically based and not due to environmental or epigenetic effects D. guarantees that some individuals will not be recombinant for the mutant locus and the marker loci on either side of it E. protects against revertant alleles that can arise spontaneously in previously mutagenized individuals

B

Which statement is true about congenital malformations? A. they are only caused by recessive mutations B. they are caused by mutations affecting many different genes and chromosomes C. they are less likely to cause than Alzheimer's, stroke, diabetes and flu combined D. they are often treatable with gene therapy E. they are often due to defects in chromatid pairing

B

While not surfing at the beach or tripping on LSD, Kary Mullis contributed to the development of PCR (though admittedly, he may have been thinking about PCR while doing those other activities, too). Anyway...his method allows for the amplification of small amounts of DNA and depends on the presence of: A. DNA ligase, deoxynucleotides, RNA primers B. DNA polymerase, deoxynucleotides, DNA primers C. reverse transcriptase, deoxynucleotides, DNA primers D. DNA polymerase, dideoxynucleotides, DNA primers E. DNA ligase, dideoxynucleotides, RNA primers

B

mRNAs with upstream open reading frames (ORFs) typically have: A. improved recruitment of the 40S subunit, thereby facilitating recognition of the main ORF initiator codon and increasing translation of the main ORF B. dissociation of 40S and 60S subunits before the main ORF initiator codon, thereby reducing translation of the main ORF C. incorrect Kozak sequences causing misassembly of 40S and 60S subunits and reduced translation of the main ORF D. translation of short polypeptides that improve function of the low-activity protein encoded by the main ORF E. polyadenylation motifs within the 5' UTR, allowing improved stability and longer perdurance of the mRNA overall

B

A gene is considered to be "haploinsufficient" when... A. the mutant phenotype is present in some anatomical locations but not others B. mutations lead to phenotypes in gametes but not somatic cells C. more than a single wild-type allele is required for normal development or homeostasis D. transgenes fail to rescue the phenotype E. a defective protein product interferes with normal function of the wild-type protein

C

After RNA pol II "escapes" from the Preinitiation Complex it: A. rapidly transcribes RNA along the entire gene body adding new ribonucleotides to the 5' end of the growing RNA B. transcribes a short stretch of RNA that typically includes the 3' UTR before reversing direction and beginning again at to the transcriptional start site C. synthesizes a short stretch of RNA complementary to the template strand of DNA before continuing through the gene body with the assistance of specific elongation factors D. interacts with ribosomes to promote translation of the new mRNA into protein E. removes exons from the new mRNA to ensure the only introns with coding sequence are exported from the nucleus

C

Analyses of differential gene expression by single cell RNA-sequencing often depend on: A. Capturing intact genomes from hundreds to thousands of cells at a time and then reconstructing gene expression using computational methods, with simplifying assumptions about alternative splicing as well as RNA perdurance. B. In vitro translation of RNAs to allow capture of gene products using customized "panels" of antibodies, thereby permitting detection by mass spectrometry with subsequent clustering of results in two or sometimes three dimensions to allow visualization. C. Reverse-transcribing mRNAs isolated from individual cells, sequencing cDNAs tagged according to cell-of-origin, assessing similarities and differences among transcriptomes in many-dimensional space, and then visualizing clusters of cells in two-dimensional space. D. Incubation of fixed (i.e., preserved) embryos with antisense riboprobes that simultaneously recognize as many as 10,000 different transcripts expressed at high levels, with subsequent "deconvolution" using computational approaches to resolve temporal and spatial heterogeneity in gene expression. E. Antibody-labeling of chromatin-associated proteins (like histones with specific marks) that reliably indicate transcriptional activity at many genes throughout the genome, followed by histological detection using multi-colored probes that can then allow clustering and visualizing in two-dimensional space.

C

Based on current evidence, a plausible reason that elephants don't have an exceptionally high incidence of cancer is that: A. their slower metabolism compensates for having more cells (and therefore more opportunities to get cancer) B. elephants inherited as many as 20 copies of the TP53 from their smaller, direct ancestor, the hyrax C. additional tumor suppressor gene copies, as compared to smaller mammals, allow some to be inactivated by mutation without increased tumor susceptibility D. their TP53 protein has evolved to be more efficient than the TP53 protein of smaller mammals, like mouse or human E. elephants have a healthy life style with plenty of fresh air and sunshine

C

Fanconi anemia exemplifies: A. The risk that ionizing radiation will lead to point mutations that affect mismatch repair and chromosomal integrity, leading to chromosomal deletions and depletion of blood and other stem cells. B. The importance of telomere maintenance and rejuvenation in blood (and other) stem cell derived lineages that have substantial requirements for on-going proliferation. C. The importance of inter-strand cross link repair in maintaining chromosome integrity and the consequences of chromosomal rearrangments and deletions for development and cancer susceptibility. D. The heightened risk of single nucleotide mutations associated with long-term meiotic-arrest of gametes as male humans age. E. The role of intra-strand crosslinks in stalling replication fork advancement and the consequences of defective repair mechanisms for accumulating cancer-causing point mutations.

C

How do histone acetyl transferase (HAT) enzymes promote gene expression? A. by adding acetyl groups to core promoter nucleotides, thereby enhancing RNA polymerase II binding efficiency B. by binding to cis regulatory elements distant from the gene body, thereby acting as a transcription factor C. by adding acetyl groups to specific amino acids in histone tails, reducing the affinity of nucleosomes for nearby DNA D. by sliding nucleosomes to new positions along the DNA molecule E. by acetylating the growing primary RNA transcript, allowing for increased stability and protein synthesis

C

In the context of the "RNA World" hypothesis, isolation of a "triplet" RNA polymerase demonstrated that A. the ancestral genetic material was likely replicated three nucleotides at a time B. ribozymes with replicase activity are already present in nature and so were present at the dawn of life as well C. enhanced replicase activity can be selected for in the laboratory and so may have been selected for in nature D. triplet codons were likely a very early evolutionary innovation that likely allowed for later complexity E. mRNA secondary structure prevents transcription in vitro, suggesting that triplets of deoxyribonucleotides were the "original" building blocks

C

Meiotic crossing over depends critically on: A. kinetochore-CENPA interactions B. lateral compression of chromatids by condensin I followed by condensin II C. establishment of a synaptonemal complex and activity of Spo11 D. severing of sister chromatid connections during anaphase E. HDAC- and DNMT-dependent chromatin remodeling during S phase

C

Muntjac deer (genus Muntiacus) are a nice example of how karyotypes can evolve over short period of evolutionary time. Which answer is true about this example? A. In M. muntjak there are only about 13% as many genes as in M. reevesi. B. The M. muntjak karyotype evolved from the M. reevesi karyotype through multiple chromosome fusions. C. An ancestral species split to produce both M. muntjak and M. reevesi with different numbers of fusions leading to each species. D. An ancestral karyotype as in M. muntjak, has been replaced with multiple fissions of individual chromosomes in each of three other species. E. Whole genome duplication has generated more chromosomes in cow (B. taurus) and red deer (C. elaphus) than are present in either Muntjac species.

C

Mutants for separase might be expected to have which defect? A. failure of sister chromatid cohesion during M phase B. failure of chromosome separation from spindle microtubules during prophase C. failure of chromatid separation during anaphase D. failure of chromosome replication during S phase E. failure of cohesin stabilization during G1 phase

C

Simulation analyses of gene regulation in Drosophila have suggested that: A. very precise levels of gene expression are required for normal development B. normal domains of final gene expression can be obtained even when some early genes are deleted entirely C. a wide range of parameter values produce the same final gene expression domains D. hedgehog acts upstream of engrailed to pattern segment morphology E. pleiotropic effects of early genes extend to segments and other larval traits

C

The genetic code A. has overlapping codons B. often results in functional proteins when 2 nucleotides are inserted and 1 nucleotide is deleted C. is degenerate D. is read from 3' to 5' in the mature mRNA E. all of the above

C

When generating a transgenic or mutant mouse by "classical" methods of homologous recombination, neomycin selection is important because: A. recombinant cells may be infectious B. it protects against end resection by exonucleases C. strand invasion rarely occurs outside of meiosis D. donor cells are rarely incorporated into the host blastocyst E. mutant cells in the mouse germ line would otherwise be outcompeted by wild-type cells

C

Which is contained in a gene body? A. all cis regulatory elements B. poly-A tail C. 5' untranslated region D. TATA box E. transcription factors

C

Which of the following is not involved in altering chromatin state between open and closed configurations? A. post-translation modification of histone tails B. methyl-CpG binding protein interactions C. self-splicing introns D. chromodomain proteins E. FoxA transcription factors

C

Which statement is true about forward genetic screens: A. mutations are specifcally targeted to genes that function in DNA repair B. mutations are preferentially induced in genes of interest C. mutations are induced randomly throughout the genome D. mutations are often homozygous when they first arise E. mutations are confined to coding regions

C

genetic marker locus can be best described as: A. the gene likely responsible for a new mutant phenotype B. a region of DNA that leads to a distinctive G-band in karyotype analyses C. a chromosomal location where different backgrounds can be distinguished by genotyping D. a ladder of regularly spaced fragments of DNA that allow PCR product sizes to be estimated with confidence E. none of the above

C

p53 (TP53) induces expression of: A. genes encoding proteins that promote cell survival B. genes promoting the G1-to-S transition C. the gene encoding CDK inhibitor p21 D. RNA pol II E. all of the above

C

A 2022 study investigating properties of the likely first genetic material, provided what novel observation: A. catalystic activity by DNA, allowing direct synthesis of RNA B. a role for tRNA in peptide synthesis C. peptide-dependent synthesis of RNAs having modified nucleotide bases D. peptide synthesis activity of RNAs having modified nucleotide bases E. DNA replication activity of of RNAs having modified nucleotide bases

D

A major innovation in second generation sequencing as compared to first generation sequencing is: A. bacterial artificial chromosome assembly B. electrophoresis through a capillary C. incorporation of nucleotides with fluorescent dyes D. the use of reversible terminators E. a method for quenching 32-P radioactivity in ddNTPs

D

An important pathological role for aberrant histone modification in a pediatric glioma is suggested by A. recurrent mutations in histone 3 genes across patients that change lysine-27 to methionine B. the ubiquity of histone 3 defects across sites of tumor spread, consistent with an early step in oncogenesis C. consistent methylation of histone H3 lysine 27 across patients D. both a and b E. both b and c

D

As DNA replication proceeds A. old histones are degraded and replaced with new histones that lack post-translational modifications B. old histones are returned to chromatin and new histones are acetylated to ensure a euchromatic state in daughter cells C. old histones are degraded and new histones may be methylated to ensure a heterochromatic state in daughter cells D. old histones are returned to chromatin and new histones may be methylated to ensure local heterochromatic states in daughter cells E. old histones are returned immediately to chromatin and new histones and nucleosomes are added in G1

D

Copy number variants are a common feature of genomes (more common than even single nucleotide polymorphisms in the human genome). A nice example of a CNV that appears to have phenotypic effects is the "ridge" found on the coats of rhodesian ridgeback dogs, which can occur along with a congenital skin defect, "dermoid sinus." These traits together have been associated with a duplicated chromosomal segment that contains several genes including 3 genes that encode Fibroblast Growth Factors (FGF3, FGF4, and FGF19). Now imagine you have just adopted a rhodesian ridgeback (not easy to do!), but on taking your pup to the vet it is found to have both a ridge and a dermoid sinus. Ignoring other types of FGF genes in the genome (e.g., FGF2), what is the most likely (albeit not definitive) explanation for your pup's phenotype? A. increased FGF activity, due to a single mutant chromosome per cell B. decreased FGF activity, due to a single wild-type chromosome per cell C. decreased FGF activity due to having two copies of a wild-type chromosome D. increased FGF activity, due to the presence of as many as 12 FGF genes per cell E. decreased FGF activity, due to the presence of only 3 FGF genes per cell

D

Imagine you are interested in guinea pigs. Seriously interested in guinea pigs. So you have accumulated a large number of these walking blackboard erasers. You decide to cross one of your brown, curly hair guinea pigs with a black, straight hair guinea pig. The pups are lovely, and they have four different phenotypes: brown, curly; black, straight; brown, straight; black, curly. The presence of recombinant phenotypes (brown, straight and black, curly) most likely indicates that: A. there are two genes, both on the same chromosome, with crossing over between them B. there are two genes, each on a different chromosome C. there is single gene with different alleles that contribute to hair color and shape D. A or B E. A or C

D

Imagine you are studying a developmental process using the zebrafish system and you have undertaken a reverse genetic screen to test roles for candidate genes identified by single cell RNA-seq. You therefore plan to design and order CRISPR/Cas9 reagents, which you will inject into embryos. To have the best chance of observing a phenotype, should the gene function in the process, you ought to design your reagents to: A. induce a premature stop codon in the first exon B. interfere with RNA splicing C. block translation from mature mRNA D. prevent transcript from being made E. target 3' UTRs to block polyadenylation

D

In genetics, the term "penetrance" refers to the proportion of genotypically mutant individuals that actually express a mutant phenotype; if all genotypically mutant individuals actually look like mutants, the allele is said to be "fully penetrant." But imagine you are studying a human "disease gene" and discover a mutant allele that is only 12.5% penetrant, even when homozygous. A plausible explanation would be: A. Spontaneously arising revertant alleles allow restoration of function. B. The allele affects only non-coding sequence. C. Recombination machinery in somatic cells allows homology-directed repair using genes with similar sequences as templates. D. Alleles segregating at one or more other loci impact the degree of genetic robustness among individuals. E. The locus is affected by X-chromosome inactivation in genetically female individuals.

D

In the classic studies by Mike Levine's group on even skipped (eve) gene expression in Drosophila, a panel of "deletion" constructs was used to... A. determine which transcription factors bind to particular sequence motifs upstream of eve. B. test the roles of cis-regulatory elements that had been previously identified using computational methods applied to whole-genome sequence. C. evaluate whether nucleotides adjacent to the "optimal" cis-regulatory elements were required for gene expression. D. assess whether particular regions of sequence upstream of eve were required for reporter gene expression at specific anatomical locations. E. modify the eve locus, allowing modifications in protein distribution across anatomical locations to be assessed using an anti-Eve antibody.

D

In the context of a genetic screen, "saturation" most often refers to: A. the minimal number of F2 individuals needed to map a recovered mutant at a resolution that has been defined a priori by genetic distance B. the optimal dose of alkylating agent needed to mutagenize a certain proportion of genes in the genome C. the observation that gene products are often sufficiently abundant that many new alleles are recessive D. the plateau at which new mutant alleles can be found without these alleles representing new mutant loci E. the dosage of CRISPR/Cas9 reagents needed to yield knockouts of both alleles at a target locus

D

James Watson is known for his: A. publication describing the structure of DNA B. using unpublished X-ray diffraction data gathered by Rosalind Franklin C. racism and misogyny D. all of the above E. none of the above

D

Leading strand DNA replication involves: A. formation of Okazaki fragments B. initiation by an unusual 5'-to-2' phosphate bond C. polymerase alpha activity D. addition of nucleotides in a 5'-to-3' direction E. synthesis of a single DNA primer per chromosome

D

Pioneer transcription factors differ from most transcription factors in being able to A. reprogram states of cellular differentiation B. access their binding sites despite close associations between DNA and nucleosomes C. initiate chromatin remodeling D. all of the above E. none of the above

D

Polyadenylation of mRNA is important for: A. preventing RNase attack B. translation initiation C. ribosome dissociation D. both A and B E. both A and C

D

Recent analyses of gene regulation in an ascidian have shown that correct expression of a transcriptional reporter gene requires... A. maximally efficient binding of transcription factors to their DNA targets B. precise epigenetic coding, detectable in the form of histone marks C. core promoter sequences longer than 100 bp D. moderate affinity interactions between cis-regulatory elements and trans-acting factors E. removal of functional Otx binding sites

D

Reporter genes are useful tools for many kinds of experiments and can often be made by cloning PCR-amplified segments of genomic DNA upstream of cDNAs for fluorophores like GFP, then injecting or electroporating these constructs into early stage embryos. Nevertheless, this approach has some caveats, including: A. the cloned segment of genomic DNA may not contain all necessary cis-regulatory elements B. the temporal dynamics of reporter visibility may not match the temporal dynamics of mRNA abundance for the gene being "reported on" C. the reporter may be expressed mosaically if not isolated as a stable line in which all cells carry the construct in their genome D. all of the above E. none of the above

D

Studies of human genome variation by "trio sequencing" show that an increased incidence of point mutations is associated with increasing paternal age, in contrast to the increased incidence of aneuploidy that is associated with increasing maternal age. This sex-difference is likely a result of: A. less efficient proofreading activity of DNA polymerase in males and less efficient Dsup activity in females B. the presence of only one X chromosome in males and the presence of two X chromosomes in females C. genetic imprinting in the male germline and low telomerase activity in the female germline D. continuous replication of DNA in the male germline and delayed completion of meiosis in the female germline E. greater exposure to point mutagens in males and greater exposure to ionizing radiation in females

D

Tardigrades are pretty remarkable in being resistant to environmental insults that are lethal to humans and just about everything else. Gene discovery and subsequent experimental analyses revealed that tardigrades can survive exposure to ionizing radiation in part because they have evolved a novel Damage suppressor protein (Dsup). What evidence supports this conclusion? A. Dsup binds nucleosomes and recruits H2AX to damaged DNA B. Dsup expression induces "comet tails" in irradiated cells and expression of H2AX in control cells C. Dsup localizes to the nucleus and binds both DNA and nucleosomes D. Dsup expression reduces "comet tails" and recruitment of H2AX in irradiated cells E. Dsup localizes to the cytoplasm where it reduces formation of "comet tails" in control cells

D

The eukaryotic Pre-Initiation Complex A. can interact with core promoter sequence motifs including the TATA box and Initiator B. can assemble at enhancer elements distant from the gene body C. transcribes DNA in the 5' to 3' direction D. both a and b E. both a and c

D

The order of some molecular events in meiotic crossing-over is: A. branch migration, Holliday junction formation, phosphodiester bond cleavage, strand invasion B. strand invasion, phosphodiester bond cleavage, Holliday junction resolution, branch migration C. Holliday junction formation, branch migration, strand invasion, phosphodiester bond cleavage D. phosphodiester bond cleavage, strand invasion, branch migration, Holliday junction resolution E. phosphodiester bond cleavage, branch migration, strand invasion, Holliday junction resolution

D

Which of the following statements about chromosomal inversions is true? A. They prevent crossing-over during meiosis yet increase the frequency of recombinant phenotypes. B. They often lead to cancer within generations but mechanisms that suppress cancer over evolutionary time (e.g., tandem copies of tumor suppressor genes). C. They are lethal when paracentric but viable when pericentric. D. They often lead to reduced fertility within a generation but occasionally result in clusters of co-adapted and co-inherited alleles that evolve across generations. E. All of the above.

D

Which of the following statements about telomeres is accurate? A. their length typically decreases within families during each passing generation B. their repeating Leu-Gly codons (TTA-GGG) are binding sites for charged tRNAs C. they become shorter because repeated sequences cannot be replicated accurately D. they are rejuvenated by synthesis of DNA from an RNA template E. they are a major site of transcription initiated by pioneer transcription factor binding

D

Which of the following statements is true about cyclins and CDKs? A. cyclins remain at constant abundance across the cell cycle and complexes formed between cyclins and variably abundant CDKs permit phosphorylation of target proteins B. cyclins remain at constant abundance across the cell cycle and complexes formed between cyclins and variably abundant CDKs permit dephosphorylation of target proteins C. cyclins change in abundance across the cell cycle and complexes formed between cyclins and CDKs permit dephosphorylation of target proteins D. cyclins change in abundance across the cell cycle and complexes formed between cyclins and CDKs permit phosphorylation of target proteins E. none of the above

D

Which of the following would be reasonable strategies for proving the correspondence of a mutant phenotype and candidate gene? A. transgenesis to replace the gene product believed to be missing in an affected cell, to test for "rescue" B. production of new alleles at the candidate locus by CRISPR/Cas9 mutagenesis C. ENU or EMS screening in the mutant background to find a revertant allele from which the candidate gene could be sequenced D. all of the above E. none of the above

D

Which statement is most often true about the long-term evolution of genes following a whole-genome duplication? A. both paralogues retain their ancestral functions B. paralogues are subfunctionalized, dividing up their ancestral functions C. one paralogue acquires a novel function whereas the other retains the ancestral function D. one paralogue becomes nonfunctionalized (inactive) whereas the other retains the ancestral function E. one paralogue is expressed in a new location whereas the other is expressed in the ancestral location

D

hich statement is true of Bardett-Biedl syndrome? A. It only arises when all 19 cilia genes are mutated simultaneously. B. The mutations known identify all of the genes required for ciliogenesis in humans. C. It represents a good candidate for CRISPR-based gene therapy given the specificity of the mutations. D. It reflects the functional requirements for primary cilia in the development of many traits. E. It is observed in males only.

D

"Consanguineous" mating refers to reproduction involving individuals who are related to one another (siblings, first or second cousins, cousins once removed, etc.). A principal risk of such matings is that: A. fertility will be impacted because of increased risk of inversions B. alleles are more likely to be neomorphic C. co-dominant alleles will interfere with each other when they wouldn't normally D. pleiotropic effects of alleles will be especially strong E. deleterious recessive alleles will be brought to homozygosity

E

Counted among Mendel's several contributions is: A. a rigorous demonstration of blending inheritance B. an explanation for additive effects of alleles C. identification of the heritable material D. an explanation for sexual selection E. development of the world's first genetic model organism

E

Drosophila Antennepedia, yellow peas, "double muscle" cows and "white" axolotls are all examples of: A. recessive mutants B. hypomorphic alleles C. copy number variants D. induced mutations E. none of the above

E

Imagine you are studying mechanisms of differentiation in mouse and your preliminary observations suggest a developmental genetic program involving feed-forward regulation of several late-acting genes. You decide to make a knock-out mutant for one of these, and you do so by removing the entire locus from the targeted chromosome. You find that heterozygotes develop normally so you in-cross them to generate families that should have ~25% of individuals homozygous for the mutation. If a feed-forward regulatory architecture is really present for you cell type of interest, what do you expect to find in the homozygotes? A. Normal differentiation because of genetic redundancies. B. Normal differentiation because of gene conversion. C. Failure of differentiation because of haploinsufficiency. D. Failure of differentiation because of non-sense mediated decay. E. It depends on the specifics of the system.

E

Imagine you have just started your post-UVa internship at Viagen, a company that already clones house pets and horses for customers who have enough money. On your first day, you field a call from a prospective customer who is interested in your services because their much-beloved lamprey, Smootches, is getting old and may soon expire. So they are hoping you can preserve some cells from skin or blood for deriving a Smootches clone, when she finally passes into the long dark lamprey night. Assuming you are honest with your prospective customer, what would you say about using these cells from Smootches for your cloning services? A. Almost certainly feasible because clonal organisms have been made from differentiated cells of frogs, which are only a small evolutionary step away from lamprey. B. Should be ok, provided enough skin or blood stem cells can be isolated. C. Risky but still worth a try as any genes that might have been lost from these somatic cells would not be needed for embryonic development anyway. D. Not a good approach because only mammary gland epithelial cells can be used for cloning and despite all her other charms Smootches is just not a mammal. E. Not feasible because the genomes of Smootches' skin and blood cells cannot be counted on to have all the genes that will be need for making Smootches-Two.

E

In a typical "F3 screen" for recessive mutant alleles, the F2 generation is an important step because it: A. results in homozygous individuals that may have mutant phenotypes B. selects mutant alleles present uniquely in the germ line of F1s (as opposed to somatic cells) for subsequent propagation C. allows dominant alleles to be discarded from the screen before F3 families are contaminated with them D. ensures induced aneuploidies are not propagated into the F3 generation, in which they could lead to deviations from expected Mendelian ratios E. generates additional copies of new mutant alleles, allowing for screening of homozygous individuals in the F3

E

Mendel's Law of Independent Assortment is usually accurate in describing A. the reason some alleles are recessive B. why the two alleles of a gene are incorporated independently into gametes C. the molecular nature of genes and alleles D. the reason that parental traits seem to blend together in offspring E. the segregation of alleles at genes not linked physically to one another

E

Studies of Drosophila even skipped (eve) regulation showed that: A. transcriptional activation drives expression of eve specifically within each stripe B. transcriptional repression blocks eve expression outside of stripes C. different domains of eve expression are governed by cis-regulatory elements arranged in discrete clusters within the genome D. both A and B E. both B and C

E

The "wobble position" allows A. the usage of alternative Kozak sequences B. the use of more abundant amino acids in place of less abundant amino acids C. transcriptional read-through of premature stop codons D. recognition of different intron splice acceptor and splice donor sequences E. promiscuous base-pairing and fewer tRNAs than codons

E

The classical "Central Dogma" of molecular biology states that: A. RNA is transcribed into DNA, which is translated into protein B. DNA is translated into RNA, which is transcribed into protein C. DNA is translated into protein, which transcribed into RNA D. DNA is transcribed into RNA, which is transcribed into protein E. none of the above

E

The discovery that some individuals are resistant to malaria owing to a single DNA base change shows that: A. GATA transcription factor expression is very sensitive to T > C mutations B. pioneer transcription factors are equally important to expression of parasite genes and host genes C. Duffy chemokine receptor depends only on GATA transcription factor binding D. there is a strict code for transcription factor binding sites, similar to the genetic code for amino acids E. none of the above

E

What sequence of events is shared among DNA mismatch repair, nucleotide excision and base excision pathways? A. recognition, endonuclease activity, DNA polymerization B. exonuclease activity, recognition, DNA polymerization C. DNA polymerization, endonuclease activity, recognition D. recognition, DNA polymerization, exonuclease activity E. recognition, exonuclease activity, DNA polymerization

E

Which feature is essential in a prototypical genetic material? A. encodes information in nitrogenous bases B. can be translated into protein C. can be replicated without error D. uses phosphate as a linker molecule E. none of the above

E

Which of the following are potential consequences of single nucleotide alterations? A. truncated protein product B. amino acid replacement C. mis-splicing of RNA D. altered transcriptional efficiency E. all of the above

E

Which of the following can explain pleiotropy? A. A gene is tightly linked to another on the same chromosome. B. A gene product acts in more than one genetic pathway. C. A gene is required in several different cell types. D. Both A and C. E. Both B and C.

E

Which of the following statements is true about histological analyses of gene expression (also known as "in situ hybridization", examples of which have been shown in class for mouse and zebrafish embryos)? A. The method demonstrates the spatial distribution of a protein product. B. The method relies on computational tools to infer levels of transcript likely to be present in cells that were not adequately sampled. C. The method is similar to reporter analyses as both show the distribution of a gene product while the animal (or plant) continues to develop. D. The method can often demonstrate cell lineage relationships. E. The method is limited to detecting mRNAs for one or a few genes at a time.

E

Which statement is false: A. miRNAs often target transcripts of more than one gene B. miRNAs can block ribosome translocation C. miRNAs regulate mRNA abundance D. miRNAs code for several different proteins E. miRNAs are transcribed initially as longer transcripts

d