Genetics 371B, Autumn1999 -- Exam 3

Genetics 371B, Autumn 1999

Exam 3: December 13

Answer key is here.

Open book, open notes, 100 points total. Answer questions 1-5 and either 6 or 7 but not both.

1.
(16 pts) Coloration in a highly fictitious species of tree frog is determined by the frg genes as shown in the pathway below. Wild-type frogs are green with pink speckles.

What phenotype do you expect with regard to coloration in frogs that are homozygous for null mutations of the following genes? (A null mutation in a gene completely eliminates that gene's activity.)

frg1 _________________________________________________________

frg2 _________________________________________________________

frg3 _________________________________________________________

frg4 _________________________________________________________

2. (20 pts) Height in a species of plant can vary between 10 cm and 50 cm, and depends on the contribution of four genes -- A/a , B/b , D/d , and E/e, where upper case alleles are contributing and lower case alleles are non-contributing. Assume that all additive alleles contribute equally to plant height.

(i) How much does each contributing allele add to plant height? (4 pts)

(ii) How many height classes are possible in this species? (4 pts)

(iii) A true-breeding 20 cm plant was crossed to a true-breeding 40 cm plant. The F1 progeny were all 30 cm tall. These F1 plants were selfed, and the F2 progeny fell into nine height classes. Give the genotype of the F1 progeny and one possible set of parental genotypes that explains the cross. (Show your calculations.) (12 pts)

3.
(16 pts) Misregulation of transcription of the STAR gene in humans leads to a disease called adrenal hypoplasia. Mutations that cause this disease are often recessive loss of function mutations in DAX-1, which encodes a transcription factor* that binds in the promoter region of STAR and regulates its transcription.

*transcription factor = a protein which binds near or in a promotor and either activates or represses transcription

(i)
FOR THIS QUESTION, ASSUME THAT DAX-1 MUTATIONS CAN BE EITHER DOMINANT OR RECESSIVE. The situations below show possible functions for wild type DAX-1. For each function, two possible effects of mutation are given. Next to each mechanism, indicate whether, for that case, the adrenal hypoplasia mutation would be dominant or recessive. (12 pts)

WILD TYPE DAX-1 FUNCTION: transcriptional repressor

MUTATION EFFECT: always active repressor, or "super repressor"

DOMINANT or RECESSIVE? _____________________________

MUTATION EFFECT: inactive repressor

DOMINANT OR RECESSIVE? _____________________________

WILD TYPE DAX-1 FUNCTION: transcriptional activator

MUTATION EFFECT: always active activator

DOMINANT OR RECESSIVE? _____________________________

MUTATION EFFECT: inactive activator

DOMINANT OR RECESSIVE? _____________________________

(ii) In one family transmitting adrenal hypoplasia, affected individuals have no mutation in DAX-1. In this family, the mutation causing adrenal hypoplasia is in the promoter region of the STAR gene. Explain how this mutation may cause misregulation of STAR transcription if DAX-l is an activator of STAR transcription. (4 pts)

4.
(16 pts) During the off-season, Santa has been investigating the genetics of reindeer nose color. But now that it's holiday season, it's up to you (his li'l helper) to keep the experiments going while he is off scooting up and down chimneys. From his lab notes, you can tell that he was working two possible models:

...where A and B are independently assorting genes regulating the steps indicated.

According to Santa's lab notebook, the cross:

AaBb x AaBb (upper case = wild type alleles, lower case = null alleles)

gave the result that "there are three times as many black-nosed progeny as red-nosed progeny". (Santa had neglected to write down how many pink-nosed progeny there were.) Which of the two models do you think is correct? To support your answer, fill in the table below to show the predictions for each model (progeny genotypes and ratios, and phenotypes predicted in each model for those genotypes).

Progeny genotypes and ratios Predicted progeny phenotypes

Model 1 Model 2

Correct model (circle 1): Model 1 Model 2

5. (14 pts)

(i) You heard in lecture about the identification of maze-dull and maze-bright lines of rats. Suppose you are studying learning behavior in two groups of rats that have been raised in similar environments. One group is highly inbred, while the other is derived from a large, randomly mating population. Which groups do you think will show higher heritability for maze-learning, the inbred group or the heterogeneous group? Why? (6 pts)

(ii)
A behavioral geneticist identifies two mutations (d1 and d2 ) that seem to cause rats to be maze-dull. How would you determine whether these two mutations are alleles of the same gene, or are mutations in separate genes? Show the cross you would do and the expected progeny phenotype(s) for each possibility (same gene vs. separate genes). (8 pts)

Cross:

Results if d1 and d2 are alleles of the same gene:

Results if d1 and d2 are mutations in two separate genes:

Answer #6 or #7, but not both. If you answer both, we will only grade #6.

6. (18 pts) In response to DNA damage, the mammalian checkpoint protein p53 activates p21, which blocks the cell cycle. Most mutations in p53 result in increased risk of cancer. However, a rare mutation (called p53*) is discovered that decreases the risk of cancer (i.e., the cancer rate is lower among individuals with this mutant allele).

(i) Suggest an explanation for how this mutation might lead to decreased cancer risk. Indicate whether you expect the mutant phenotype to be dominant or recessive (i.e., does a p53+/p53* heterozygote have the normal level of risk, or reduced risk?). (6 pts)

(ii) The frequency of the p53* allele in a certain population is 1/1000. What fraction of this population do you think will show reduced cancer risk if the Hardy-Weinberg model applied here? (Assume that your answer in part (i) is correct with respect to dominant vs. recessive mutant phenotype.) (8 pts)

(iii) Based on what you have been told about the property of the p53* allele, why might the Hardy-Weinberg model NOT apply in this population? -- i.e., which assumption of the Hardy-Weinberg model might not hold? (4 pts)

Answer #6 or #7, but not both. If you answer both, we will only grade #6.

7. (18 pts) Red-green colorblindness is an X-linked recessive trait in humans. In a certain population, 10% of the men are red-green colorblind. For the following questions, assume that the population shows Hardy-Weinberg frequencies.

(i) What percent of the women are expected to be colorblind? (5 pts)

(ii) What percent of the women are expected to be heterozygous carriers? (5 pts)

(iii) In a different population (also showing Hardy-Weinberg frequencies), 20% of the women are heterozygous for red-green colorblindness. If an affected man marries an unaffected woman of unknown genotype, what is the probability that their first child will be colorblind? (8 pts)

1.	(16 pts) Coloration in a highly fictitious species of tree frog is determined by the frg genes as shown in the pathway below. Wild-type frogs are green with pink speckles. What phenotype do you expect with regard to coloration in frogs that are homozygous for null mutations of the following genes? (A null mutation in a gene completely eliminates that gene's activity.)
	frg1	_________________________________________________________
	frg2	_________________________________________________________
	frg3	_________________________________________________________
	frg4	_________________________________________________________

2.	(20 pts) Height in a species of plant can vary between 10 cm and 50 cm, and depends on the contribution of four genes -- A/a , B/b , D/d , and E/e, where upper case alleles are contributing and lower case alleles are non-contributing. Assume that all additive alleles contribute equally to plant height.
	(i)	How much does each contributing allele add to plant height? (4 pts)
	(ii)	How many height classes are possible in this species? (4 pts)
	(iii)	A true-breeding 20 cm plant was crossed to a true-breeding 40 cm plant. The F1 progeny were all 30 cm tall. These F1 plants were selfed, and the F2 progeny fell into nine height classes. Give the genotype of the F1 progeny and *one possible set of parental genotypes* that explains the cross. (Show your calculations.) (12 pts)

6.	(18 pts) In response to DNA damage, the mammalian checkpoint protein p53 activates p21, which blocks the cell cycle. Most mutations in p53 result in increased risk of cancer. However, a rare mutation (called p53*) is discovered that decreases the risk of cancer (i.e., the cancer rate is lower among individuals with this mutant allele).
	(i)	Suggest an explanation for how this mutation might lead to decreased cancer risk. Indicate whether you expect the mutant phenotype to be dominant or recessive (i.e., does a p53+/p53* heterozygote have the normal level of risk, or reduced risk?). (6 pts)
	(ii)	The frequency of the p53* allele in a certain population is 1/1000. What fraction of this population do you think will show reduced cancer risk if the Hardy-Weinberg model applied here? (Assume that your answer in part (i) is correct with respect to dominant vs. recessive mutant phenotype.) (8 pts)
	(iii)	Based on what you have been told about the property of the p53* allele, why might the Hardy-Weinberg model *NOT* apply in this population? -- i.e., which assumption of the Hardy-Weinberg model might not hold? (4 pts)

7.	(18 pts) Red-green colorblindness is an X-linked recessive trait in humans. In a certain population, 10% of the men are red-green colorblind. For the following questions, assume that the population shows Hardy-Weinberg frequencies.
	(i)	What percent of the women are expected to be colorblind? (5 pts)
	(ii)	What percent of the women are expected to be heterozygous carriers? (5 pts)
	(iii)	In a different population (also showing Hardy-Weinberg frequencies), 20% of the women are heterozygous for red-green colorblindness. If an affected man marries an unaffected woman of unknown genotype, what is the probability that their first child will be colorblind? (8 pts)