Genetics 371B, Autumn 2000

Problem set 3 -- based on lectures 14-19

Due Mon Nov. 13 at the start of class

Note changes to Q. 2 and Q. 5. -- 11/3/00

1. Linkage analysis was done for a certain human disease gene with respect to polymorphic loci PL1, PL2, PL3, and PL4. Some of the resulting Lod scores are plotted. Each curve represents the lod score vs. recombination frequency distribution for a polymorphic site with respect to either the disease locus (D) or with respect to one of the other polymorphic sites. For example, Curve #1 shows the lod score vs. recombination frequency between the disease locus D and polymorphic site PL1.
(a) Why do all the curves approach lod score = 0 as the recombination frequency approaches 50%?
(b) Interpret Curve #3, stating whether there is significant evidence for or against linkage between the two loci. If there is significant evidence, give the approximate minimum and/or maximum distance in cM between the two loci.
(c) Construct a linkage map that is consistent with the data shown. Your map should include all five loci, but they need not all be on the same linkage group. Briefly explain how you arrived at your conclusions.

2. Look back the experiment of Harriet Creighton and Barbara McClintock to demonstrate that crossing over leads of recombination (p. 35 of your lecture notes). To do that experiment, they had to know which chromosome carried the colored and waxy endosperm traits. Here is a version of the experiment that identified the chromosome carrying the colored endosperm trait (again, R = colored endosperm, r = colorless). A homozygous RR strain was crossed to ten different strains (call these the "P1 parents"); each of these 10 strains was trisomic for a different chromosome and all were homozygous recessive for endosperm color. Trisomic progeny from each cross were picked out and crossed to disomic rr plants. The progeny obtained are shown on the right. Assume that trisomics in corn are viable (at least with one chromosome at a time being trisomic).

Which chromosome carries the endosperm color gene? Explain your logic.

3. Continuing with corn plants: Resistance (F) to a certain fungus is a dominant phenotype in corn, while sensitivity (f) is recessive; the gene is located on chromosome 10. A corn plant that was homozygous for a reciprocal translocation between chromosomes 5 and 10 and for the disease resistance allele was crossed to a normal fungus-sensitive plant. The F1 plants were resistant to fungus and were semisterile. When these F1 progeny were testcrossed to the normal (non-translocation) parent, the following progeny were obtained:
112 semisterile, sensitive
128 normal, resistant
869 semisterile, resistant
891 normal, sensitive
(a) Diagram chromosomes 5 and 10 as they would appear at metaphase of Meiosis I in the F1 plants.
(b) How far (in cM) is locus F/f from the translocation point? Your answer should explain the results (the phenotypes and the relative numbers).

4. Five recessive mutations on the right arm of the X chromosome of Drosophila cause stringy bristle (sg), lazy eyes (ly), tin body (tn), zillion eye (ze), and miniature wing (m) phenotypes. The genes for lazy eyes, tin body and zillion eyes are known to be located between the stringy bristle locus and the miniature wings locus, and tn is known to be closer to sg than to m, but the gene order of ly, tn and ze is not known.

Embryos were exposed to X-rays and then allowed to develop to adulthood; the males were mated separately with (non-irradiated) females showing all five recessive traits. [Call these the P1 matings.]

(a) Most of the matings produced normal females and sg ly tn ze m males in equal proportions. One of these phenotypically normal females, when mated to a male sibling, produced F2 progeny that consisted solely of normal and fully mutant phenotypes (males and females in equal proportions). Why was this result unexpected, and how do you explain it?
(b) One of the P1 matings produced sg ly tn ze m males and ly tn females in equal proportions. Explain the result.
(c) One of the other P1 matings produced sg ly tn ze m males and ly ze females. What is the map order of ly, tn and ze? What is the map order of all five genes?

5. The Great Northwest Pizza Mold grows as a pizza-shpaed mat of diploid, filamentous cells (hyphae). Four new recessive mutations in linked genes were discovered in this mold: g (green) is recessive to the normal white (G); f (fat hyphae) is recessive to the normal thin (F); r (rough) is recessive to the normal smooth (R); and airborne (a) sends up hyphae upward instead of the normal horizontal (A). A quadruple heterozygote was obtained by crossing a homozygous wildtype strain with a strain homozygous for all four recessive phenotypes. Spots of the following recessive phenotypes were seen in the pizza-shaped mat of the resulting heterozygote:
(i) 60 lone green spots
(ii) 30 green spots, each next to a spot of rough hyphae
(ii) 30 green spots, each also consisting of rough hyphae
(iii) 15 lone spots of fat hyphae
(iv) 3 spots of fat hyphae, each next to a spot of airborne hyphae
(iv) 3 spots of hyphae that were fat and airborne

Green, airborne spots or rough-, fat-hyphae spots were never observed.

(a) What can you conclude about the order of the four loci relative to the centromere? If a traditional (meiotic) mapping experiment reveals that the green locus is 6 cM from the rough locus, what do you expect the genetic map of the region to be? (Show the loci, the centromere, and the approximate map distances you might expect between them.)
(b) After an exhaustive search of pizza mold "pies" of this heterozygous strain, a few lone spots of rough hyphae and one lone spot of airborne hyphae are discovered. Diagram a recombination-based mechanism to explain these spots. (Your answer has to be consistent with your map in part a!)