CM156-Midterm II-Winter 2020-KEY

1 Name (Last) (First) Student ID KEY CM156/256 Midterm Exam II (February 24, 2020) Circle your discussion section for return of the exam: Gregory Maria 1 (40pts) 2 (10pts) 3 (10pts) 4 (10pts) 5 (10pts) 6 (10pts) 7 (10pts) Show your work for full credit. Include only information pertinent to the question. (40pts, 1. Select the best answer for each of the following questions: 4pts each) A. Differences in gene expression between male and female cells typically include all EXCEPT : i) Autosomal genes regulated by ovarian hormones ii) X-inactivated genes iii) Genes that escape X-inactivation and have a partner on the Y chromosome that has evolved independently iv) Genes that escape X-inactivation and do not have a partner on the Y chromosome v) Genes in the male-specific region of the Y chromosome B. If an allele is under positive selection, this will affect nearby SNPs in terms of: i) Allele frequencies ii) Recombination rates iii) Mutation rates iv) Genetic drift v) Linkage C. The Hardy-Weinberg law can be expanded to more than two alleles, as in the case of the blood groups. In the case of blood groups, “O” is recessive to A and B. What is the frequency of type “B” individuals if the frequencies of alleles A, B, and O are 0.4, 0.4, and 0.2, respectively? i) 0.16 ii) 0.24 iii) 0.32 iv) 0.42 v) None of the above D. Twin studies have been a valuable way to determine whether a trait has a genetic component. Such evidence is based on which of the following findings? i) Increased frequency of the trait in dizygotic twins as compared with monozygotic twins ii) Increased frequency of the trait in monozygotic twins as compared with dizygotic twins iii) Equal frequency of the trait in monozygotic and dizygotic twins iv) Increased frequency of the trait in monozygotic twins as compared with the general population v) Increased frequency of the trait in monozygotic twins exposed to different environments

2 E. Despite that fact that height is highly heritable, men are substantially taller than women. This indicates that: i) Heritability is not the same in men and women ii) Environmental factors that interact with genetics are responsible iii) Men and women differ in genetics iv) Hormones are responsible for the differences v) All of the above F. In studies of multiple sclerosis, an autoimmune disorder, the recurrence risk in sibs and offspring of affected persons was found to be 15% while the risk in nieces and nephews was less than 2%. The most likely mode of inheritance is: i) Autosomal dominant ii) X-linked iii) Autosomal recessive iv) Mitochondrial v) Complex G. Sickle cell anemia patients from different ethnic backgrounds share the same haplotype of the β -globin locus. This suggests that: i) The mutation exhibits a “gain of function” ii) The mutation has been under strong positive selection iii) The mutation occurred only once in history iv) The mutation is most likely recessive v) The mutation is an example of a triplet repeat disease H. Which of the following is NOT TRUE about common disorders such as schizophrenia and cancer? i) They are often cluster in families ii) They frequently exhibit significant differences between sexes iii) Family studies can be used to estimate their heritabilities iv) The frequencies of common diseases frequently differ between ethnic groups v) The genetic component is always larger than the environmental component I. Which of the following applies to individuals with genetic cancer predisposition syndromes? i) They may develop cancer at later ages than those with sporadic cancers ii) They are unlikely to redevelop cancer upon surgical removal of a primary tumor iii) They inherit mutations in proto-oncogenes iv) They may develop cancer upon loss-of-heterozygosity of the region carrying the inherited mutation v) They are unlikely to have siblings with cancer J. Steps that could be used to identify the causal SNP variant in a GWAS signal include all of the following EXCEPT : i) Analysis of the locus for epigenetic marks indicating regulatory sequences ii) Identification of all SNPs in linkage disequilibrium with the lead SNP (the SNP with the lowest p value) iii) Identification of interacting regions using chromosome conformation capture iv) Following the segregation of each SNP in affected and unaffected individuals v) Identification of transcription factor binding sites within the locus

4 (10pts) 4. The following figure shows DNA sequence variation in 10 individuals (20 chromosomes) across a 5 kilobase section of the genome on chromosome 5. (4pts) A. Excluding the 5 low frequency variants and the deletion represented on the next to last chromosome, how many major haplotypes are present on the figure? Five or six (3pts) B. For the 8 th haplotype from the top, how can you explain the presence of the “C” low- frequency variant? A new mutation occurred on the chromosome (3pts) C. The haplotypes represented by the pink box are associated with a particular common disease that has a strong genetic component. Do you think that the variant that underlies the association occurred before or after the recombination that yielded the haplotypes that include the pink box and repeat polymorphism variants? We decided that the question was ambiguous and gave credit for both before and after.

5 (12pts) 5. The following Figure is from the Kemaladewi et al. paper from Week 4. Based on the Figure and your knowledge of the study, answer the following questions: (3pts) A. Why was the endogenous Lama1 gene not able to rescue the phenotype in the absence of the vector? Lama1 is not normally expressed in muscle (3pts) B. Why was SadCas9 used instead of the wild-type Cas9? To prevent cleavage of the DNA at both the Lama1 locus and possibly off-target loci (3pts) C. For the single guide experiment, what was the purpose of the Flag tag? To follow gene expression using Flag antibody as a measure of expression from the construct that is independent of Lama1 (3pts) D. What was the role of the VP64 element in the construct? Through its function as a transcriptional activator, to mediate gene expression at the targeted locus