Total (90) Problems 1-4 (12) Problems 5 &6 (14) Problem 7 & 8 (14) Problem 9 (10) Option 1 or 2. Option 1-4 (14) Option 1-4 (14)
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1 Biol 321 Spring 2011 Final Exam [90 points] NAME REMEMBER: carefully inspect problems and pay attention to detail! YOU ARE NOT ALLOWED TO USE CALCULATORS OR CELL PHONES DURING THIS EXAM or to send or receive signals of any kind READ EACH QUESTION CAREFULLY BEFORE ANSWERING. This exam is divided into two sections: Section 1: 50 pts total. You must answer every question in this section Section 2: 12 pts total. You must answer one of two options Section 3: 28 pts total. You must answer two of four options Problems (pts.) Score Section 1 50 pts Problems 1-4 (12) Problems 5 &6 (14) Problem 7 & 8 (14) Problem 9 (10) Section 2 12 pts Option 1 or 2 Section 3 28 pts Option 1-4 (14) Option 1-4 (14) Total (90) 1
2 Section 1 (50 pts.) 1. (4 pts.) It is estimated that SNPs are found in 0.1% of all the base pairs in the human genome. a. Translate the acronym SNP b. How many total SNP sites would be found in a single copy of the human genome? Show your work, track units and circle your answer. No credit if no work or no units. 2. (3 pts.) The enzymatic components of the post-synthesis mismatch repair system are encoded by the mutator (mut) genes. Based on your understanding of how genes have been traditionally named, briefly explain this apparent contradiction. Be sure to indicate the wildtype function (generally) of these genes. 1-3 sentences using proper terminology. 3. (2 pts.) Which statement(s) is(are) false about the STR loci used for DNA fingerprints. a. They are under weak evolutionary constraints b. Different alleles show codominance c. They represent regions of the genome with scattered repeats due to transposable element duplication and movement d. They are inherited like any standard Mendelian allele e. They have a relatively high mutation frequency 4. (3 pts.) State and briefly explain one difference in the association mapping strategy used to identify the CCR5 polymorphism in HIV resistant individuals and the positional cloning strategy used to identify the pain/no pain gene. Three sentences maximum 5. (11pts.) Circle T or F for each statement. Answer false any part of the statement is false. If there are two statements, the first statement is true and you are to decide if the second statement is T or F. 1 pt if no explanation required. 2 pts if an explanation required. T F In the appropriate context, a loss-of-function allele may also be considered a polymorphism One sentence explanation 2
3 T F By definition, a loss-of-function mutation can never be a neutral mutation. One sentence explanation: T F Excluding silent and neutral missense, most mutations in the proto-oncogene class of genes will result in driver alleles. One sentence explanation: T F The tumor suppressor class of genes (often found mutated in cancer cells) are named for their gain-of-function phenotype. T F Because of the the asexual nature of a cancer cell lineage, the number of passenger mutations can only increase in the descendants of a cancer cell lineage and never decrease. One sentence explanation: Recall the article GENOME DARK MATTER. By each statement circle True/False/subject Not addressed in this article. Answer false if any part of the statement is false. T F N Even though non-coding DNA is often considered junk DNA, vast stretches of this junk DNA are conserved between mice and men. T F N Although scientists expected to find 100,000 genes in the human genome the current count is between 40,000 and 50,000 genes per single copy. 6. (3 pts.) As species go, humans aren't renowned for their sense of smell. But an improved ability to suss out scents in our 200-million-year old ancestors may have laid the groundwork for the bulging brains of humans and all other mammals. Virtual three-dimensional 'casts' of the fossilized skulls of animals that preceded the first true mammals suggest that brain areas involved in smell, or olfaction, catalysed brain growth in the evolutionary branch that gave rise to mammals. The olfactory system was the thing that drove the expansion of the brain in the first place, and once you've got a big brain you can do all kinds of things with it," says Timothy Rowe, a palaeontologist. What did you learn in the chromosome 11 fly over that supports the statements in bold. Be explicit. 2-3 sentences. 3
4 7. (8 pts.) A map of the Drosophila X chromosome is shown on the data sheet (pg 1). Check your work carefully before selecting your answer. Partial credit possible. (i).(4 pts) A female of genotype m + g / m g + is crossed with a phenotypically wild-type male. All female progeny are wild-type. The percentage of male progeny that will have miniature wings and garnet eyes is: a. 4% b. 8 % c. 46% d. 92% e. 50% f. 100% g. not enough info to determine h. none of the above (ii) (2 pts) A female heterozygous for both the sable body and garnet eye genes is crossed with a phenotypically wild-type male. All female progeny are wild-type. The percentage of male progeny that will have both sable bodies and garnet eyes is: a. 0.5% b. 1 % c. 49.5% d. 99% e. 50% f. 100% g. not enough info to determine h. none of the above (iii) (2 pts) A female of genotype sc + lf + / sc lf is crossed with a phenotypically wild-type male. All female progeny are wild-type. The percentage of progeny males that will be wild type for both traits is: a. 0% b. 16 % c. 25% d. 34% e. 50% f. 68% g. not enough info to determine h. none of the above 8. (6 pts.) Page 3 of the DATA sheet shows data from a paper describing the positional cloning of a gene associated with microcephaly. True/False/Not enough Info to decide. Answer false if any part of the statement is false. If there are two statements the first statement is true and you are to decide if the second statement is true or false. Unless otherwise indiated, 2pts if explanation required; 1 pt if no explanation T F N These researchers used a positional cloning strategy to identify the specific gene that was mutated in this disease state. This suggests that from the very beginning of the project the researchers had a hunch as to what type of protein the gene coded for. One-two sentence defense of your answer. T F N Unaffected family members are heterozygous for some but homozygous for other poymorphic sites. Problem 8 continues on the next page 4
5 T F N Since affected members of Family 2 are homozygous for a different haplotype from Family 1, it is likely that this family is segregating a mutation in a different gene. One sentence defense of your answer. T F N The disease gene appears to be located in a region between D8S1824 and D8S (10 pts) Gorlin syndrome is an autosomal dominant disorder that predisposes affected individuals to various cancers and developmental defects, which are obvious at birth. Examine the pedigrees on pg 2 of the DATA sheet. B1, B2 and B3 are alleles of a site (called D9S29) that maps to chromosome 9. A genotype of B1 means that the individual was homozygous for B1. (Likewise for B2 and B3). Each pedigree represents a different kindred group. Assume the disease shows complete penetrance and that the D9S29 polymorphism is 4 map units from the gene mutated in Gorlin syndrome. a. In kinship 2601, there is a B2B3 individual in generation III and one in IV. One has the disease the other does not. Briefly explain why assuming that neither is the result of a meiotic recombination event. 1-2 sentences. b. In kinship 2102, the B1B2 male from generation II contacts you for some advice. His wife is expecting their third kid and a prenatal test indicates a genotype of B1B2. First: write out the genotypes of the parents using notation for linked genes. Second: Caluculate the probability that the kid is heterozygous for the Gorlin mutation. Show your work and circle your answer. c. Examine kinship group Here are two possibilities for the genotype of the first generation: affected male B2B2 X unaffected female B1B2 OR affected male B1B2 X unaffected female B2B2 Examine the entire pedigree. Which scenario is most likely? Circle your choice. No explanation required. 5
6 Section 2 Work EITHER this question OR the question on the next page. Section 2 Option 1 (12 pts) See pg 4 of data sheet about Prader-Willi syndrome. (i). Examine the gel. What does the difference in PCR product length represent? In other words, what is the molecular basis of the polymorphism. One sentence. (ii). Examine the pedigree and gel data on the extra sheet. What is surprising about the genotype of the affected child (#2)? Be explicit. (iii). Non-disjunction refers to a situation where either paired homologs or sister chromatids fail to separate during a cell division. The gamete that #2 received from his mother was produced by non-disjunction of chromosome 15 during meiosis in her germline. Assuming no crossing-over between the site of the microsatellite polymorphism and the centromere, in which meiotic division did the non-disjunction event occur? Circle the correct answer: a. Meiosis I a. Meiosis II c. either Meiosis I or II d. not enough info to determine Defend your answer with a labelled diagram and one or two sentences of text. Don t show all stages of meiosis - - just the most relevant one(s). Be sure to label division and stage. (iv) Now assume that a cross-over event did occur between the site of the microsatellite polymorphism and the centromere. In which meiotic division did the non-disjunction event occur? Circle the correct answer: a. Meiosis I a. Meiosis II c. either Meiosis I or II d. not enough info to determine Defend your answer with a labelled diagram and one or two sentences of text. Don t show all stages of meiosis - - just the most relevant one(s). Be sure to label division and stage. (v) Reread the introduction to the problem. Why does #2 have PWS? 2 sentences max. 6
7 Section 2 Option 2 (12 pts) Do NOT work this question if you worked Opton 1 on the previous page See article on page 5 of the DATA sheet Part A: (5 pts) Indicate True, False or N (not enough information provided to assess). If you choose N, indicate what additional information you would need. T F N Assuming all cases of ALS are genetically determined, the article implies that this disease state is genetically heterogeneous (or shows genetic heterogeneity). One sentence explanation/defense of your answer: T F N The studies described in the article suggest that there are other genes (in addition to Nox-1 and Nox-2) that can influence expression of the ALS mutation. T F N Although not stated explicitly in the article, the results of the studies suggest that polymorphisms affecting the activity of the Nox-2 gene could result in variable expressivity or incomplete penetrance of SOD1 mutations in humans. One sentence explanation/defense of your answer: Part B (3 pts.) In one succint sentence using correct terminology, state the specific type of gene interaction that is described in this article. Be sure to address dominance. Part C: (4 pts) Your mom reads about this particular research project on the internet one day and s you expressing her indignation at the money and time spent on a mouse project given that the issue at hand is the treatment of a human disease state. In a 2-5 sentence response persuade your mom that the time and money are likely to have been well spent. Be explicit as possible with your arguments 7
8 Section 3 (28 pts): This section consists of four 14 pt problems. You must answer TWO of these problems. If you answer or attempt to answer more than two problems, you must indicate which ones I should grade. Otherwise, I will grade the first two questions that have answers. 1. Essay Choice A or B : Putting together pieces of the genetic puzzle or Popeye 2. Direct Detection of Mutation: The GATA gene 3. Fruitflies and Genotype Crunching 4. SNPs, STRs and DNA fingerprints Option 1 If you work this option, choose ONE of these Essay Topics Putting together pieces 0f the genetic puzzle OR I am what I am Put your answer on an extra sheet of paper.. Choice A Putting together pieces 0f the genetic puzzle Examine the figure on pg 6 of the DATA SHEET. This figure was taken from a review article on the genetics of addictive behaviors. You are charged with writing an article for the New York Times that includes this figure. Examine it carefully and write a detailed legend to the figure (in essay form) explaining/interpreting panels A and B. Be sure to address all aspects of each panel. Your answer should be several sentences long and should thoroughly explain each type of symbol and the difference in patterns in A and B. Be sure to address the underlying causes of the double-circled symbols You must use proper terminology. See the data sheet for a list of terms that may apply to this figure. Be sure to use all appropriate terms in an appropriate context. Choice B I am what I am See cartoon on pg 6 of data sheet. Fully explore Popeye s statement in the context of what you have learned this quarter about the relationship between genotype and phenotype: Be sure to address both simple (mongenic) and complex traits. Illustrate each of your major points with specific examples. At least one example should be relevant to the cartoon in a general sense at least. You can use hypothetical examples; be imaginative but don't let your creativity get in the way of the science. Figure/diagrams are fine but you must also include text that explains it/them. NOTE: this is a serious question. Your essay will be graded on content, coherence and the proper use of scientific/genetic terminology. Hints for writing an effective essay: Your essay should be in paragraph form. A bulleted list of talking points is not sufficient. Use proper genetic terminology. Take some time to organize your thoughts and start with a list of points that you want to make. NOTE: your answer should be in essay form -- the list is for you. 8
9 Section 3 Option 2 Data Analysis: Direct detection of genotype Mutations in the GATA gene result in heart defects, immune deficiencies, deafness and renal malformations -- also known as HDR syndrome. The figures on pg 7 of the Data Sheet illustrate direct detection of genotype in two different families with mutations in the GATA gene. Based on the information presented here indicate whether each statement is T F N (True/ False/Not enough info to decide). State false if any part of the statement is false. Two points if explanation required; 1 pt if no explanation required. T F HDR syndrome is genetically heterogeneous. T F N HDR is a pleiotropic, autosomal syndrome. T F N Based on family 26/99, the HDR syndrome is incompletely penetrant. Defend/explain your answer in one sentence. T F N In both families the mutant alleles are likely to result in a gain-of-function. Defend/explain your answer in one sentence. T F N In family 12/99, the mutant allele is codominant at the molecular level of assessment but dominant (completely or incompletely) at the organismal level of assessment.. T F N The mutant GATA allele is recessive in Family 26/99 and dominant in Family 12/99 One sentence defense of your answer: T F N Setting niceties aside, if individual II #1 from family 26/99 mates with I #2 from family 12/99, the probability of a normal offspring is 1/4. T F N If the parents in either family have additional children, there is a 50:50 probability of an affected offspring. One sentence defense of your answer T F N The GATA gene is likely to be X-linked. One sentence defense of your answer: 9
10 Section 3 Option 3 Fruitlfies and Genotype Crunching You find two fruitflies (one wild-type female and a doubly mutant male) crawling around on some bananas at home and, inspired by your Biol 321 course, you decide to mate them and deduce the mode of inheritance of each trait. Questions are on the next page Trait wild-type allele symbol mutant allele symbol wings w + = winged w = wingless (wings absent ) (wings present) can still mate OK eye shape e + round e = oval You do the following crosses and score lots of F1s: P winged & round female X wingless & oval male F progeny flies are scored MALES and FEMALES BOTH: 1/2 wingless & round 1/2 winged & round You then cross : winged & round F1 female X winged & round F1 male F progeny flies are scored: all females are winged & round 1/2 males are winged & round 1/2 males are winged & oval 10
11 Section 3 Option 3 continued Carefully examine the data shown on the previous page and work through a genotypic analysis using the allele symbols indicated in the table. a. Which traits are dominant? (no explanantion necessary) b. Is the wing gene autosomal or sex-linked? (no explanantion necessary) c. Is the eye shape gene autosomal or sex-linked? (no explanantion necessary) d. Using the designated alleles symbols, on the previous page clearly indicate the GENOTYPES OF the parental and F1 generations and F2 generations. e. Predict the outcome of the following cross. OUTCOME = genotypes and ratios. F1 wingless & round female X F2 winged & oval male 11
12 Section 3 Option 4 SNPs, STRs and DNA Fingerprints Examine the figure on pg 8 of the DATA SHEET. Note that the info in the table is aligned with and refers to the marker types to the left. a. SNP s are typically assayed using PCR and a restriction enzyme. Given your understanding restriction enyzmes how many different alleles can be distinguished for a single SNP marker? # of alleles Briefly explain. 2 sentences and/or a labelled drawing. b. STR = In the genotyping strategy that we discussed in class, are restriction enzymes used in genotyping STR loci? Circle: YES NO Briefly explain. 2 sentences c. Would an SNP locus have more or less discrimination power relative to an STR locus? Twothree sentence answer/explanation including a statement explaining the discrimination power of SNPs d. There is a comment in the SNP column that the mutation rate is low. Why does this comment not appear in the STR column? Fully explain (3-4 sentences). Use proper jargon but no drawings necessary here. e. Note the table lists Mutation only as a source of variation for sites on the Y chromosome. Why is recombination not a source of new genetic variation for Y chromosome markers? f. Is this statement true true for all loci/sites on the Y chromosome? Circle YES or NO One sentence explanation. g. What does megabase mean? 12
Section 1 Pg 2 (16) Pg 3 ( 6) Pg 4 ( 8) Pg 5 (10) Pg 6 (10) Section 2: Option 1 (15 pts.) Option 2 (15 pts.) Total out of 80
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