B) Is Wolbachia an example of cytoplasmic inheritance? Justify your answer.
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1 GENETICS 603 EXAM 3, Dec. 1, 2006 NAME 1. Retinoblastoma in humans was long considered to be a dominant trait with reduced penetrance, since not every child who inherited the gene developed the cancer. What is the actual situation as far as the inherited form of retinoblastoma is concerned? Almost all familial cases result from a deletion on one copy of the RB gene: if the second copy of this tumor suppressor gene mutates in a developing retina cell, cell division continues and the tumor forms. 2. A recent speaker at a Genetics seminar suggested that crossovers initiated early in synapsis of homologous chromosomes play an important role in making sure that the kinetochores of the homologues find and remain attached to spindle fibers from opposing poles. Connect this observation with the relatively high frequency of trisomy-21 births seen in humans. First, 21 is a short chromosome so there may not always be a crossover present. Meisois I begins in human females soon after conception, arrests until at least puberty and then resumes years later as each ovarian follicle matures. Since the frequency of trisomy 21 increases greatly with maternal age, perhaps the lack of crossovers (if true) permits more detachments with time. The translocation type of trisomy could also lead to problems as there may be 3 centromeres rather than 2 pairs, but these account for only a small portion of the trisomy 21 births. 3. Many species of insects are infected with Wolbachia sp, which are rickettsia-like bacteria that are passed through the egg. Sperm of infected males are inactivated from fertilization unless Wolbachia are present in the egg. A) Predict the population-genetics effects of Wolbachia on the host species. The theory is that since Wolbachia (W) infected females can mate with either infected or non-w males, they will be more fit (higher reproductive rate) than non-infected so that W will spread through the population (much as the P-element has spread in Drosophila. I would certainly accept other answers, such as evolving to 2 separate populations or that W makes the mosquitoes less fit, but that would then require explaining why they are so prevalent. B) Is Wolbachia an example of cytoplasmic inheritance? Justify your answer. It is cytoplasmically transmitted, but technically is infectious heredity since it is not one of the essential organelles that contains DNA. C) Recently it has been shown that Wolbachia injected into Aedes aegypti cause the same fertility characteristics in this mosquito species. It has been suggested that Wolbachia may prove useful in preventing the spread of dengue fever from a virus carried by Aedes aegypti. What is the rationale for this claim, and how might a prevention plan be implemented? The primary concept requires establishing a W+ population of A. aegyti and then releasing it in high dengue fever areas where it would take over bsed on increased fitness. The bacteria would also be engineered to prevent virus replication in the cytoplasm.
2 4. A trisomic Datura plant has a Dwarf gene D on the trisomic chromosome that is dominant even if present in only one copy. Predict the phenotypic ratios for progeny of DDd by Ddd reciprocal crosses if a) disomic eggs are functional but not pollen DDd female by Ddd male Ddd female by DDd male Eggs\Pollen 1 D 2 d Eggs\Pollen 2 D 1 d 2 Dd 2 DDd 4 Ddd 2 Dd 4 DDd 2 Ddd 1 DD 1 DDD 2 DDd 1 dd 2 DDD 1 ddd 1 d 1 Dd 2 dd 1 D 2 DD 1 Dd 2 D 2 DD 4 Dd 2 d 4 Dd 2 dd 1 Tall : 8 dwarf 1 tall 6 dwarf b) both disomic eggs and pollen are functional. (Since male female gametes will make the same ratiosn, reciprical crosses will be the same) Eggs\Pollen 1 D 2 Dd 1 dd 2 d 2 Dd 2 DDd 4 DDdd 2 Dddd 4 Ddd 1 DD 1 DDD 2 DDDd 1 DDdd 2 DDd 1 d 1 Dd 2 Ddd 1 ddd 2 dd 2 D 2 DD 4 DDd 2Ddd 4 Dd 3 of 36 (1:12) will be tall 5. The term threshold disease has been applied both to quantitatively and cytoplasmically inherited traits. Explain how the term applies to these 2 very different types of inheritance, and give an example of each if possible. Thresholds in quantitative traits occur when any individual with more than a specific number of contributing alleles has an all or none trait (for example schizophrenia). In cytoplasmic traits, most individuals are heteroplasmic, and since the organelles distribute by chance into daughter cells or eggs, only tissues or individuals with a threshold level of defective (mitochondria in the case of MERF for example) exhibit the symptoms. 6. Lebers hereditary optic neuropathy (LHON) is always associated with a point mutation in one of the 13 protein encoding genes in human mtdna. However, not everyone with the mutation has LHON, and the disease is seen 5 times more often in males than females. Propose a model that will account for these facts. Since all mt-coded proteins are parts of proteins that interact with nuclear components, the simplest model would be to say that the LHON mutation can be seen only in the presence of a recessive allele of a gene on the X chromosome that encodes another of the interacting components. Even if the X-linked allele is common, say in 20% of the males, it would only be homozygous in 4% of females
3 7. A shepherd has a random mating flock of 200 sheep (100 each sex) where of the rams have horns and of the ewes are hornless. Not realizing the mechanism of inheritance involved, but knowing that he would like to have all males with horns and hornless females, he sells off the hornless males and horned females before producing the next generation of progeny. A) Give a legend that describes the inheritance of horns in these sheep. Male horns horns hornless H H H H HH Female horns hornless hornless B) What are the allele and genotype frequencies in the original herd. allele f(h ) = 0.5, f(h) = 0.5, genotype:.25 H H : 0.5 H H: 0.25 HH C) What will happen to the gene and genotype frequencies in the progeny generation? sperm 1/3H 2/23 H eggs 2/3 H 2/9HH 4/9H H males 7 horns:2 non 1/3 H 1/9H H 2/9H H females 2 horns:7 non D) Suppose the same selection protocol is applied the next generation. What will the male and female progeny in the following generation look like, with regard to horns? males 151 horned : 45 hornless females 151 polled:45 horned 8. Genetic tests of adults in a fairly large and fairly closed society in Senegal where malaria remains a problem showed 626 homozygous for Hb- A / Hb- A, 249 heterozygous (Hb- A / Hb- S, and 0 adults with sickle cell anemia Hb- S /Hb- S. a) Calculate allele and expected genotype frequencies for this population. 1501/1750 = f(hba) = 0.858; f(hbs) = genotypes expected under HW.7357 AA :.2411 AS :.0202 SS b) How would you test for Hardy-Weinberg equilibrium? Chi square test for the 3 classes; sum of (observed-expected)/expected with 1 df c) Calculate relative fitness value for each genotype: Hb- A / Hb- A Hb- A / Hb- S Hb- S /Hb- S (by definition) 0 since none survive (for AA, 626/644 is fraction expected surviving, then divide by 1.16 to normalize the heterozygotes to 1) d) If an anti malarial vaccine can be developed, what will happen to the gene frequencies? What would the eventual equilibrium value of the Hb- S allele be predicted to be? Since the heterozygote is no longer favored but the Hb S Hb S is still lethal, the S allelel should decline to the square root of the mutation rate (selection against recessive lethal) e) Now suppose that that effective treatment for sickle cell anemia is also found. Predict the eventual equilibrium genotypic frequencies for the Senegal population in this case. It should go to equilibrium immediately (no force acting other than forward and reverse mutations) ie AA : AS : SS
4 9. The coefficient of inbreeding F can be defined several different ways. a) Give 2 of them. fraction of heterozygosity lost due to inbreed ing probability an offspring carries 2 copies of the same ancestral allele by common descent b) Show that q 2 + pqf = q 2 (1-F) + qf q 2 + pqf = q 2 + (1-q)qF =q 2 + qf q 2 F =q 2 (1-F) + qf c) How can (1-F) in this equation be defined, and what is the significance of writing the expression this way? fraction of heterozygosity not lost; allows to break into RM and inbreeding effects 10. What is a P-element? Explain how P elements have been used to develop a transformation system, and why it works. A transposable element that has spread through the wild Drosophila population and becomes active only in germ line cells in progeny of females that do not have a repressor (an alternate spliced product of the transposase in their eggs. For transformation, other genes, often including an eye color gene as a marker, replace the transposase between the terminal repeats in one copy, and another copy with a functional transposase but defective terminal sequences (or just the enzyme) is also injected into the egg. 11. Drosophila from one valley are homozygous for the gene/chromosome arrangement A B C D E F G J K L M N while those from another valley are homozygous for the following arrangement a) What aberrations separate one population from the other? pericentric inversion and reciprocal translocation b) Show synapsis in a hybrid progeny, c) What factors will affect fertility of the hybrid? What % fertile gametes might be expected for hybrid males and females? crossover in inversion, alt vs adjacent segregation in the translocation 25% in each
5 12. The histograms below show the distribution of seed weight of a mixed population of beans and the effect of one generation of selection. 1) What are the values for the selection differential, the response and heritability? Sel Diff = 288.2; Response = 205.6, h 2 = ) If you repeated the selection over several generations would heritability remain the same? Explain No, as more contributing alleles accumulate and become homozygous, less of the variation seen will be attributed to segregating genes
6 14. A truebreeding rice plant from a cultivar that averaged 18 tillers per plant was crossed to another that on average produced 10 tillers. F1 progeny averaged 14. a) Rare (3 or 4 in a thousand) plants with 6 or 22 tillers were observed in the F2 progeny. How many genes are segregating for tiller number in the F1? 4 b) According to your answer to a: 1) how many tillers result from each contributing allele? 2 2) how many different tiller-number phenotypes would be expected in the F2? 9 c) Is there transgressive segregation in this example? Explain yes, the F2 extremes exceed the values of the parents d) Give potential genotypes for the parental plants and the F1: F1 hybrids A A, B B, C C, D D 10 tiller parent A A BB CC DD 18 tiller parent AA B B C C D D e) If the variance in the parents and F1 was 2 while that in the F2 was 10, calculate or show the values for V T 10 V G 8 V E 2 e) What is the heritability of tiller #? h 2 = What are some of the attributes that make C. elegans a good model organism for studying development? transparent, every cell visible so cell fates available, small genome, rapid life cycle, lazar ablation, self or cross possible, Tn mutation stocks available, etc 16. The genes bicoid and nanos play key roles in early Drosophila development. What do they do? When and where do they do it? (A diagram can help you answer.). bicoid mrna in egg accumulates at anterior pole, when expressed the protein is a TF that turns on or off other genes. It is also a translation inhibitor for messages such as caudal so also establishes a reverse gradient. Nanos is a maternal gene whose mrna collects at the posterior terminus of the egg and inhibits translation of specific genes bicoid anterior posterior 17. Very briefly define the following: Ne: effective population size HOX gene: highly conserved genes with 60 amino acid (homeobox) domains involved in regulating formation of body head to tail QTL quantitative trait locus LOD score Log of the Odds, ie ratio of the odds of obtaining data under the hypothesis (for example map distance derived from data) over the odds the distribution occurred by chance Robertsonian translocation: fusion (or reverse) of two one armed chromosomes into 1 bi-armed ITS region: internal transcribed spacer, in rdna used for species specific identification Amphidiploid: Plants like cotton that have 2 full sets of chromosomes originating from different species
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