b. (3 points) The expected frequencies of each blood type in the deme if mating is random with respect to variation at this locus.

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1 NAME EXAM# 1 1. (15 points) Next to each unnumbered item in the left column place the number from the right column/bottom that best corresponds: 10 additive genetic variance 1) a hermaphroditic adult develops from a single zygote 2) analytical assignment of a phenotype to a gamete 2 average excess 3) average deviation of individuals from the population mean 4) breeding value of a genotype 17 Bonellia 5) calculated as the square root of the variance 6) chemical process catalyzed by a gene product 28 broad-sense heritability 7) correlation between parents and offspring for a quantitative trait 8) correlation between siblings for a quantitative trait 20 g AB g ab = g Ab g ab 9) equals the dominance variance plus the epistatic variance 10) equals the narrow-sense heritability multiplied by the total phenotypic 25 norm of reaction variance 11) equals the narrow-sense heritability when nonadditive genetic variance 8 1 / 2 h / 4 σ 2 d/σ 2 p is large 12) evolve more rapidly than nonsynonymous substitutions for protein / 2N coding genes 13) Fisher's model for the analysis of genetic variance for a quantitative trait 29 persistence of fetal hemoglobin 14) Fisher's model for the analysis of phenotypic variance for a quantitat trait 16 p 2 + 2pq + q 2 + 2pr + 2qr + r 2 15) frequencies of the alternative alleles in a gene pool 16) Hardy-Weinberg equilibrium genotypic frequencies for a locus with 3 27 (p 2 + 2pq)/q 2 alleles. 17) illustrates the importance of environment on development of the adult 14 σ 2 p = σ 2 g + σ 2 e phenotype 18) less likely than nonsynonymous substitutions to be selectively neutral 23 scurvy 19) linkage disequilibrium 20) linkage equilibrium 5 standard deviation 21) long-term rate of neutral evolution for an autosomal DNA sequence 22) measures the strength of genetic drift in a population for an autosomal 12 synonymous substitutions locus 23) occurs when a common genetic deficiency and a rare dietary deficiency coincide 24) occurs when a rare genetic deficiency and a rare dietary deficiency coincide 25) phenotypic values associated with a genotype across varying environmental and genetic backgrounds 26) rate at which a newly arisen dominant allele will increase in frequency in a population 27) ratio of a dominant to recessive phenotype in a population at Hardy-Weinberg equilibrium 28) ratio of the total genetic variance to phenotypic variance within a generation 29) shows epistatic interaction with the sickle-cell allele in some human populations 30) shows genetic dominance over the sickle-cell allele in heterozygous individuals

2 NAME EXAM# 2 2. (10 points). Frequencies of the three MN blood types are given for a hypothetical human deme: M MN N Total Calculate each of the following parameters from the information provided. a. (3 points) The frequencies of alleles M and N in the deme. Freq (M) = ( )/2000 = 0.6 Freq (N) = ( )/2000 = 0.4 (or = 0.4) b. (3 points) The expected frequencies of each blood type in the deme if mating is random with respect to variation at this locus. Freq M type = (0.6) 2 = 0.36 (or 360 individuals) Freq MN type = 2(0.6)(0.4) = 0.48 (or 480 individuals) Freq N type = (0.4) 2 = 0.16 (or 160 individuals) c. (3 points) The chi-square value used to test the hypothesis of random mating using these data. ( ) 2 /360 + ( ) 2 /480 + ( ) 2 /160 = = (rounding to 2 or more decimals accepted) one d. (1 point) The number of degrees of freedom used in the chi-square test of part c.

3 NAME EXAM# 3 3. (13 points) For each of the following statements, name the concept or principle described. a. The two parameters needed to describe a normal distribution. mean and variance or mean and standard deviation b. A standardized measure of covariance that varies from -1 to +1. correlation or correlation coefficient c. Varying genes that each make a small contribution to variation of a quantitative phenotype in a population. quantitative trait loci or QTLs (either singular form also acceptable) d. A site in the genome at which two different bases occur as the common alternative alleles in a population. single nucleotide polymorphism or SNP e. The separation time in millions of years required to evolve 1% amino-acid sequence divergence between homologous proteins. unit evolutionary period or UEP f. Movement of genes among demes of the same species by migration of individuals prior to mating. gene flow g. Occurrence of a population bottleneck associated with establishment of a new geographic deme in the history of a population. founder event or founder effect h. Evolutionary change caused by sampling error inherent in finite population size. genetic drift or random genetic drift i. A mathematical parameter used to measure the average rate of coalescence of alleles in a population. inbreeding effective size or inbreeding effective population size j. An evolutionary force whose main consequence is to introduce many rare alleles into a population. mutation k. A name for the probability that two alleles selected at random from a population are not identical by descent. heterozygosity l. Sewall Wright's model of population structure in which geographically distant populations do not exchange alleles directly but may do so indirectly using intervening populations as "stepping stones." isolation by distance m. Sewall Wright's statistic used to express the proportion of allelic diversity partitioned among rather than within local populations of a species. F ST

4 NAME EXAM# 4 4. (20 points) The following data are used for an analysis of variance in LDL cholesterol levels (measured in mg/dl of blood serum) associated with genotypes at the ApoE locus. Allele frequencies at the ApoE locus are: allele 2 (0.1), allele 3 (0.8) and allele 4 (0.1). Mating is random with respect to variation at the ApoE locus. Include appropriate units of measurement in answers. LDL-chol a. (3 points) What is the frequency of each genotype in the population? b. (2 points) What is the mean LDL cholesterol level of the population as a whole? = 76(0.01) + 84(0.16) + 90(0.02) + 100(0.64) + 100(0.16) + 100(0.01) = = 97 mg/dl. c. (3 points) Provide the genotypic deviations for each genotype all in mg./dl. d. (2 points) Provide the total genetic variance for LDL cholesterol in this population. = 0.01(-21) (-13) (-7) (3) (3) (3) 2 = = mg 2 /dl 2 e. (3 points) Calculate the average excesses of each allele in this population. allele 2 = 0.1(-21) + 0.8(-13) + 0.1(-7) = mg./dl. allele 3 = 0.1(-13) + 0.8(3) + 0.1(3) = 1.4 mg./dl. allele 4 = 0.1(-7) + 0.8(3) + 0.1(3) = 2.0 mg/dl. f. (3 points) Provide the additive genotypic deviations for each genotype mg./dl. g. (2 points) What is the additive genetic variance for LDL cholesterol in this population? = 0.01(-26.4) (-11.8) (-11.2) (2.8) (3.4) (4.0) 2 = = mg 2 /dl 2 h. (2 points) What is the dominance genetic variance for LDL cholesterol in this population? = = mg 2 /dl 2

5 NAME EXAM# 5 5. (10 points) Sequencing 650 bases of a locus whose variation is associated with susceptibility to lupus yields 22 variable sites producing 23 haplotypes. The haplotype tree illustrates relationships among the haplotypes (numbered circles) and the numbered sites at which base substitutions occurred on each branch. Haplotype 1 is ancestral using outgroup comparison. Size of the circle is proportional to frequency of the haplotype in the population: haplotype 17 (0.30), 10 (0.30), 21 (0.11), 2 (0.05), 18 (0.05), 1 (0.02), all others (0.01 each). Recombination is absent among these haplotypes. a. (2 points) What are the frequencies of the ancestral and derived alleles at site 89? ancestral = 0.87 derived = 0.13 b. (2 points) From a visual inspection of the haplotype tree, which pair of variable sites is expected to s the highest linkage disequilibrium in this population? 7 and 500 c. (2 points) For the pair of sites chosen in part b, which of the numbered haplotypes have the ancestral condition at both sites? 1-9 d. (2 points) For the pair of sites chosen in part b, what is the value of linkage disequilibrium measured by D? D = [ (0.01)][ (0.01)] - 0 = (0.5)(0.36) = 0.18 e. (2 points) Using the general methodology of a haplotype-tree scan, what groupings of haplotypes wou used as alternative alleles A1 and A2 to test for an effect of the substitution at site 7 on susceptibility to lupus? A1 = haplotypes 1-16, A2 = haplotypes or vice versa

6 NAME EXAM# 6 6. (10 points) We saw evidence in class for genetic epistasis between the ApoE locus and the LDLR locus for levels of LDL cholesterol in blood serum: alleles 3 and 4 of ApoE have equivalent phenotypes when the LDLR genotype is A 1 _, whereas allele 4 of ApoE is genetically dominant over allele 3 for higher serum cholesterol in individuals whose LDLR genotype is A 2 A 2. Answer each of the following questions with respect to this variation. a. For a population in which allele 4 of ApoE is fairly rare (frequency = 0.15) and the A 2 allele of LDLR is very common (frequency = 0.78), which locus will show higher broad-sense heritability for serum LDL cholesterol level? ApoE b. For a population in which allele 4 of ApoE is very common (frequency = 0.95) and the A 2 allele of LDLR is much less common (frequency = 0.50), which locus will show higher broad-sense heritability for serum LDL cholesterol level? LDLR c. What component of genetic variance can be estimated using a measured genotype approach on these loci studied together but not individually? epistatic variance d. Starting with the population described in part a and keeping the allelic frequencies at the ApoE locus constant, what change in allelic frequency at the LDLR locus would eliminate additive genetic variance associated with the ApoE locus for serum LDL cholesterol? fix allele A1 in the population or eliminate allele A2 from the population or make A2 extremely rare e. What general principle regarding causally complex systems is illustrated both by variation at these loci and incidence of phenylketonuria in human populations? confoundment of frequency and apparent causation 7. (4 points) State the hypothesis being tested in the ALIVE study, and what subject data you examined to test the hypothesis. The hypothesis is: the presence of an SI mutation in more the half of the HIV sequences present in an HIV-positive patient is associated with a severely compromised CD4 cell count (< 200 cells/ul). The hypothesis was tested by aligning and examining HIV sequences from a given patient to see how many sequences had the SI mutation. This was then compared to the CD4 count of that patient at the same visit.

7 NAME EXAM# 7 8. (8 points) Using the Evolve program, you examined the relationship between genetic drift, time and population size. Answer the following questions relating to that exercise: a. (3 points) What trend in allele-frequency changes did you observe that correlated with decreasing population size and increasing generation time? How was change in allele frequency measured? A greater change in allelic frequency is observed as generation time increases and population size decreases. Allele-frequency change was measured as the observed allele frequency less the starting allele frequency (observed freq - 0.5). b. (3 points) For what conditions were you most likely to see loss of variation? How was loss of variation evident in the results? Loss of variation was most likely with the smallest population and the longest generation time. In our experiment, loss of variation means that the frequency of the A allele goes to either zero or one. c. (2 points) If thousands of trial were run, what average change in allele frequency would you expect for N=40 at generation 50? Explain your answer. Average allele frequency change should be zero. This is because drift is just as likely to cause an allele frequency to go up as down, so over many trials, the average change should be zero. 9. (10 points) a. (8 points) In our artificial selection experiment with Brassica rapa, we used two methods to estimate heritability, response to selection and parent-offspring regression. Briefly describe how you calculated heritability with each method. Response to selection: first, calculate the mean trichome number value for G1, parental, and G2 populations. Then use the following formula to estimate heritability: h 2 = (G2 mean - G1 mean) (P mean - G1 mean) Parent-offspring regression method: Plot a graph with mother trichome number on the X-axis and offspring trichome number on the Y-axis. Find the slope of the best fit regression line. Use the slope and the standard deviation calculated for the mother and offspring populations in the following formula: h 2 = 2 x slope x (s x ) s y b. (2 points) We could make our heritability estimate from the parent-offspring regression method more accurate by making a change in the experimental protocol. Describe the change. (Hint-not something trivial like count trichomes more accurately). If we controlled the cross-pollination of the 10 selected parents such that we knew the trichome number of the mother and the father for each G2 offspring plant, the heritability calculation would be more accurate.