Name. oe Test son Tea) Fists on Tae) ete Fe optoaly Student # Signature. UNIVERSITY OF TORONTO. Faculty of Arts and Science DECEMBER 2011 EXAMINATIONS HMB265H1F General & Human Genetics Duration — 2 hours. Examinations Aids: Non-Programmable Calculator only This exam is out of 90 marks. Instructions: Write your full name and student number on every page of the exam. Part 1- Multiple Choice (40 questions worth 2 marks each, total 80 marks) 1.1 Answer the multiple choice questions on the scantron. 4.2 Refer to the "MARKING INSTRUCTIONS: on the scantron for information on filling it out (eg., use HB pencil; no stray marks anywhere on the scantron), 1.3 In the "FORM" box on the scantron, indicate which "FORM" (A, B, C or D) is indicated on the top of your exam page. 4.4 Fill in SIGNATURE, SUBJECT and DATE on the scantron. 1.5 Correctly bubble in your STUDENT NUMBER, LAST NAME and INITIALS on the scantron. Part 2- Short Answer (2 questions worth 10 marks total) 2.1 Answer all questions using complete, concise sentences and writing legibly using ink only in the lined space provided on this paper. Good lu d Invigilators are not permitted to interpret questions for individual students. if you think that a question is ambiguous, answer as you understand it, then make a note here. Please be specific.HMB265HIF Final Exam 2011-12 FORMA ‘Name, Student # Part 1--MULTIPLE CHOICE. Choose the one answer that best answers the question, 40 questions worth 2 marks each, total 80 marks. 1) A cross is performed between two mice that have the following genotypes at three unlinked autosomal loci: Mouse 1, Aa;BB;cc and Mouse 2, Aa;bb;Cc. If the cross produces two offspring, what is the probability that both offspring will have the dominant phenotype at all genes? A) 9/64 B) 3/64 ©) 9/32 D) 916 2) Kathy has an X-linked recessive disease. Which of the following statements is correct? A) Her mother’s father most likely has the disease. B) Her father’s father most likely has the disease. C) Her father’s mother most likely has the disease or is a carrier. D) Her mother’s mother most likely has the disease or is a carrier. 3) Lisa is studying the EGF receptor tyrosine kinase. She creates a mouse strain with a deletion of most of the extracellular domain. What result would you predict? A) decreased cancer susceptibility B) increased affinity to epidermal growth factor C) decreased expression of ErbB oncoprotein D) increased kinase activity 4) A female mouse inherits a maternal chromosome containing a mutation in the insulator element preventing CTCF from binding to the DNA. What would be the predicted result of this mutation? A) increase in body size B) hypermethylation of DNA. C) decrease in body size D) no change in body size 5) Gene therapy trials performed to treat patients with X-linked recessive OTC (ornithine transcarbamylase) deficiency illustrated one of the challenges involved in gene therapy. What was the challenge? A) insertion of transgene into functional gene B) immune responses to viral vectors ©) difficulty of transferring DNA into ceils D) sufficient expression of transgene Page | of 15HMB26SHIF Final Exam 2011-12 FORMA Name Student #, 6) A cross is performed between an AA individual and an aa individual to produce F individuals. One F; individual is selfed, and a random F) individual is selfed again. What is the probability that the first F3 individual is homozygous? A) 9/16 B) 3/4 o14 D) 3/16 7) In deletion mapping experiments, fruit flies homozygous for different deletions in a chromosomal region were generated and crossed with fruit flies that were homozygous for mutations in specific genes within the region. The regions deleted (represented by the lines in Panel A) and the results of the crosses (Pane! B) are shown in Figure 3 at the end of the exam. What is the order of genes a to g that are located in positions 1 to 7 on the chromosome? 8) Holly inherits a loss-of-function mutant allele of a paternally imprinted gene from her father. Loss of function of the gene is associated with a particular disease. Will Holly have the disease, and ‘what percentage of her children (if any) will have the disease? A) Yes; none of her children will have the disease. B) No; none of her children will have the disease. C) Yes; 50% of her children will have the disease. D) No; 50% of her children will have the disease. 9) The normal sequence of 9 genes along a chromosome is ABCD+EFGHI (where « represents the centromere). A person is found to be an inversion heterozygote, with one normal copy of th chromosome, and another with the sequence AFE*DCBGHI. A single crossover event occurs during meiosis between two non-sister chromatids in the segment between the C and D genes. ‘What products could result from this crossover event to produce gametes that were NOT viable? A) ABCDsEFA and IHGFE*DCBGHI B) ABCDCBGHI and IHGFE*D*EFA C) ABCCBGHI and IHGFE*DD+EFA. D) ABCD*EFBA and IHGFE*DCGHI Page 2 of 15HMB265HIF Final Exam 2011-12 FORMA Name. Student # 10) Researchers identified a mutation that increases diabetes risk, but only 20% of individuals with the mutation got diabetes. What is this an example of? A) variable expressivity B) pleiotropy C) incomplete penetrance D) epistasis 11) Coat colour in a breed of dogs shows dominant epistasis, where B is epistatic to A and the dominant B allele produces a yellow coat colour. In the absence of the dominant B allele, the dominant A allele produces a black coat colour and the recessive a allele produces a brown coat colour. A cross is performed between an 4ABb individual and an AaBb individual. What proportion of the offspring is expected to have black coat colour? A) 14 B) 1/2 36 D) 9/16 12) A group of researchers conducted a genome-wide association (GWA) study to identify genes associated with human height in Japanese populations. The results of their experiments are shown in Figure 2 at the end of the exam, What can one conclude based on this information? A) The LCORL gene is most highly associated with human height. B) There are only a few major genes affecting height in humans, each having a large additive effect. C) Genes associated with height in Japanese populations remain constant when assessing other populations. D) The IGFI gene is not associated with human height. 13) A recessive disease is being studied in mice to determine if the disease gene is linked to a known gene controlling coat colour. An inbred strain of mice with the disease and recessive yellow coat colour is crossed with an inbred wild-type strain without the disease and with black coat colour. Fy individuals are then backcrossed to the diseased parental line, and for the Fz progeny 45% of them have the disease and a yellow coat, 45% of them have no disease and a black coat, 5% of them. have the disease and a black coat, and 5% of them have no disease and a yellow coat. What best describes these results? A) The genes are unlinked. B) The genes are completely linked. C) The genes are linked and 5 cM away from each other. D) The genes are linked and 10eM away from each other. Page 3 of 15HMB26SHIF Final Exam 2011-12 FORMA Name___ Student # 14) A researcher in the Niagara region is working with a particular species of grape that is normally diploid, with two sets of eight chromosomes. In the lab, he adds colchicine to mitotic cells of early grape plant embryos, and allows the plants to develop to maturity. If these plants grown in the lab are allowed to self-fertilize, how many chromosomes would you expect to find in the somatic cells of their progeny? A)8 B) 24 ©)32 D) 16 15) A particular Drosophila embryo has two inactive copies of the bicoid gene, and has a mother carrying one wild-type and one mutant copy of the bicoid gene. What is the predicted expression pattern of Caudal protein in this embryo? ‘A) expressed in the posterior region only B) expressed in the anterior region only C) no expression D) expressed throughout the embryo 16) Ishraq is a third-year undergraduate student working in a lab that studies Streptococcus pneumoniae. He conducts a mutagenesis experiment which yields 6 mutant strains unable to synthesize a particular compound required for their growth, Each of these 6 strains contains a mutation in a different gene that blocks a different step in a particular biosynthetic pathway. In order to grow, these mutants require that a compound be supplied in the medium that a wild-type Streptococcus pneumonia strain is able to synthesize for itself, Table 1 at the end of the exam shows results from experiments in which the mutants were grown in media supplemented with the indicated compound. What is the order of the compounds used in this biosynthetic pathway, from earliest to latest? A)A>C3HSESG>B—D B)G+B>4D>A4C>E>H OQBSG5D5C5ASHSE D)E>H>A>C>D>G>B Page 4 of 15HMB265H1F Final Exam 2011-12 FORM A Name. Student # 17) Jen is a 4% year undergraduate student working in a plant lab. She is studying roses, and identifies three independently-assorting genes, R, S, and T, that contribute to the production of thorns on the stems of roses. The R/ allele adds 3 thorns; the R2 allele adds 6 thorns; the S/ allele adds 5 thorns; the S2 allele adds 9 thorns; the 7/ allele adds 10 thorns; and the 72 allele adds 14 thorns. Jen crosses roses of genotype R//R2; S1/S2; T1/T2 with roses of genotype R2/R2; SI/SI; TVT1. What thom numbers would she expect to see in the progeny? A) 42, 43, 46, 50, 52, 54 B) 39, 42, 43, 46, 47, 50 ©) 39, 42, 46, 50, 51 D) 42,47 18) A species of giant octopus found in the Indian Ocean is diploid, and has a total number of 54 chromosomes in somatic cells. A scientist caught a member of this species of octopus and used karyotypé anaylsis to show that it had nullisomy 3, trisomy 8, and tetrasomy 10. How many chromosomes would you expect to find in the nucleus of a somatic cell from this octopus? A) 56 B)57 ©)28 D) 55 19) The chromosomes of a translocation heterozygote pairing during meiosis are shown in Figure 4 at the end of the exam. Which of the following gametes would result from the adjacent-2 segregation pattern, and are the gametes viable? A) IKL*ERG, BCD-EFG; not viable B) BCD*EFG, BCD+MNO; not viable C) BCD-EFG, JKL*MNO; viable D) JKL*EFG, JKL+*MNO; viable 20) A genetic map for three X-linked genes in Drosophila was known to be ~30¢M------G-—-—-30cM—-H. A cross is performed between an FFGGhh female with a male that is fgH/'Y. If'an F; female is backcrossed to the male parent, what proportion of the male progeny is expected to be {GH/Y, assuming no interference? A)AS% B) 45% 1% D) 9% Page 5 of 15HMB26SHIF Final Exam 2011-12 FORMA Name__ _ Student # 21) Samia is a graduate student studying transposable elements in maize. She observes a strain of com with the Ds element inserted into the C gene, but no Ac element is present in the genome. What phenotype would Holly most likely observe in the kemels of this strain of corn? A) pigmented B) shrunken C) colourless D) spotted 22) In the pathway shown below, genes A and B catalyze a reaction to produce the red-flower phenotype, where the dominant alleles successfully catalyze the reaction, and recessive alleles block it, A cross is performed between an aaBB individual and an 4Abd individual, and the F individuals are selfed. Which of the following statements is correct? A B White => White => Red A) Assuming independent assortment, 3/16 of the F2 progeny are expected to be white, B) If the genes are completely linked, 3/4 of the F2 progeny will be white. C) If the genes are completely linked, 1/2 of the Fz progeny will be red. D) This is an example of dominant epistasis. 23) A man with Klinefelter syndrome is diagnosed with haemophilia, an X-linked recessive disorder. Neither his father nor his mother have the disorder. When would non-disjunetion have occurred to best explain the simultaneous origin of Klinefelter syndrome and haemophilia? A) the second meiotic division in the mother B) either the first OR second meiotic division in the father C) either the first OR second meiotic division in the mother D) the first meiotic division in the father 24) A dominant disease is known to be at a frequency of 19% in the population. Assuming random mating, what is the frequency of the disease allele in the population? A) 81% B) 10% C) 19% D) 90% Page 6 of 15HMB26SHIF Final Exam 2011-12 FORM A Name. eee Student # _ 25) A mutagenesis screen is performed in fruit flies and several mutations affecting segment identity are isolated. One of the mutant strains carries a point mutation in the Antennapedia (Anip) gene, resulting in antenna-to-leg transformation. How would this mutation best be classified as? A) morphic B) hypomorphic C) hypermorphic D) neomorphic 26) Brin is studying a strain of C. elegans (nematode worms) that displays abnormal feeding behaviour. She isolates the gene associated with this behavior, and conducts a Western blot analysis. She observes that the protein encoded by this gene is larger in size in the mutant strain than in the wild-type strain used as a control. What type of mutation has most likely occurred? A) nonsense B) missense C) synonymous D) frameshift 27) Marina is a fourth-year research project student working with female breeding 4%/a mice. She feeds half of the mothers a supplemented diet rich in folic acid, and half of the mothers a normal diet. What phenotypic changes would Marina most likely observe in the mouse progeny of supplemented mothers? A) shift towards pseudoagouti coat colour B) increase in diabetes C) increase in weight ) shift towards yellow coat colour 28) Brendan is a graduate student studying the heritability of tail length in Rhesus macaques, a trait that shows continuous variation, In one macaque family, narrow sense heritability for an F3 group of siblings was calculated as 0.70, while different variances were calculated as follows: For Vg: V4=420 and V=25; and Ve=110. What is the value for variation due to dominance effects (Vp)? A) 4S B) 155 ©) 65 D)80 Page 7 of 15HMB26SHIF Final Exam 2011-12 FORMA ‘Name, Student #. 29) Emma is conducting a mutagenesis screen in Drosophila and isolates a number of mutations of the even-skipped (eve) gene. One of the mutant strains carries several small deletions in the eve stripe 2 regulatory (enhancer) element that eliminate the binding sites for Kruppel (Kr) and Giant (Gt). What would be the predicted expression pattem of Eve stripe 2 in these mutant embryos? A) narrower expression B) normal expression C) no expression D) broader expression 30) The following two questions refer to the Moore family pedigree (Figure 5 at the end of this exam), which shows two individuals with a very rare disease. Based on this pedigree, what is the likely mode of inheritance of the diseas A) X-linked dominant B) autosomal recessive C) autosomal dominant D) X-linked recessive 31) If individual IiJ-2 had children with individual I-4, what proportion of the offspring would have the disease? A) 1/24 B) 1/6 ©) 12 D6 32) Sandra is using X-rays to mutagenize Chlamydomonas, a single-cell photosynthetic eukaryote that, normally swims by means of two flagella. She screens the mutagenized population for members who lack flagella, and through this screen identifies a mutation in the gene encoding dynein. What type of mutation has Samantha most likely introduced? ‘A) thymine dimer B) base substitution ©) deletion D) splice-site mutation 33) Mojib is writing a report on the differences between cancer cells and normal cells. What modification found in many cancer cells produces uncontrolled cell growth? A) paracrine stimulation B) loss of contact inhibition C) gain of gap junctions D) increased cell death Page 8 of 15HMB265H1F Final Exam 2011-12 FORM A Name. Student # 34) The first gene therapy trial in humans was conducted more than twenty years ago. What did NOT characterize this trial? ‘A) used an ex vivo gene therapy approach B) patients lacked a functional adenosine deaminase (ADA) gene C) long-term expression of transgene detected in patients D) enzyme therapy performed concurrently 35) Two genes, A and B, are linked, and their genetic map distance is 20 cM. A cross is performed between an individual that is 44bb and an individual that is aaBB. If an F; individual is test-crossed, what proportion of the progeny would be Aabb? A) 02 B) 04 C01 D)0.8 36) Zina is studying the heritability of whisker length in Siamese cats, She calculates the broad sense heritability of this trait to be 0.75, and the narrow sense heritability for this trait to be 0.65. What does this suggest? A) The phenotype of a Siamese cat from this population is predictable based on the phenotype of its parents, B) Most of the phenotypic variation in whisker length is due to dominance and epistatic genetic effects. C) Most of the phenotypic variation in whisker length is due to environmental effects. D) The phenotype of a Siamese cat from a different population can be predicted on the basis of its parents” phenotypes. 37) Transposable elements make up a very large component of the human genome, however, the human race has been able to survive despite these mutation-inducing elements. What is NOT one of the reasons why humans are able to survive with an abundance of transposable elements in their genome? A) Insertion of transposable elements into other retrotransposons. B) Missense mutations in the transposase gene. C) Regulatory mechanisms found in gene coding regions. D) Insertion of transposable elements into centromeric regions. Page 9 of 15HMB26SHIF Final Exam 2011-12 FORM A ‘Name__ _ Student # 38) Ronald is working with a particular strain of fruit fly in the lab that has two retrotransposons in its genome. This particular strain also has two P clements in its genome, each occupying identical sites in homologous chromosomes. If both retrotransposons and one copy of the P element each undergo one episode of transposition, how many copies of transposable elements would you expect to find? A)4 B)8 O6 D)7 39) Aaron is a graduate student investigating the causes of an autosomal dominant disease in humans. He performs linkage analysis in the Cooper family that has many members affected by the disease. ‘The pedigree for this family is shown in Figure 1 at the end of the exam. The mother in the second generation is heterozygous for the dominant disease allele and for a molecular marker. For the third generation, 5 of the children are recombinant with respect to the mother’s contributing gamete. What is the LOD score for the third generation for the specific marker and disease gene? A) 1.05 B)-2.98 ©) 0.02 D)-0.96 40) Punit, a second-year undergraduate student, is interested in the genetic mechanisms of development and would like to work with model organisms during the summer. What is NOT one of the advantages of using model organisms to study development? A) easy to maintain B) long generation time ©) quick reproduction D) many progeny generated Page 10 of 15HMB265HIF Final Exam 2011-12 Name. Student # Part 2--SHORT ANSWER. 41. (6 marks) Describe the multi-hit model of cancer development. Provide three pieces of evidence presented in lecture for the multi-hit model. (5 sentence maximum) 42. ($ marks) Michael is a graduate student working in a plant genetics lab. He is investigating flowering time in rice, a quantitative trait, and wants to determine the genes responsible, What experiments should Michael perform to accomplish his goal? (5 sentences maximum) Page 11 of 15HMB265HIF Final Exam 2011-12 Name_ Figures and Tables: / ope — 0 oO | erewerzerest uct | iste -log,. (P-value) j | 2 usaoso 16Ft | ‘Chromosomal Position Figure 2: (from Okada et al., Hum. Mol. Genet. 19:2303(2010)) Page 12 of 15HMB26SHIF Final Exam 2011-12 Name, Student # Panel A m2 oS 7 Del 1 Del2 SS Del3 Del5 Del 6 Del4 _—— Panel B Det | - + E + Dei2 | - + + + + i + Del3 - + + + {Dera [Deis | Det 6 +fel+ ' + ; Figure 3: Deletion mapping experiment. Panel A: Chromosome and regions that are deleted in the deletion mutants. Panel B: Results from the cross described in the question. (+) indicates the phenotype is wild-type and (-) indicates the deletion uncovers a recessive mutant allele. Page 13 of 1SHMB265HIF Final Exam 2011-12 Name__ : Student # ng during meiosis. | Compound added ‘Table 1: Growth in media with the supplemental compound is indicated by (+), no growth is shown by (-). Page 14 of 15HMB26SHIF Final Exam 2011-12 Name. Student # u 1m Figure 5: Pedigree for the Moore Family ‘Total Pages = 15 Total Marks = 90 Page 15 of 15