Medical Genetics 4th Edition by Lynn B. Jorde -Test Bank

Chapter 8: Gene Mapping and Identification

Sample Problems & Essay Questions

Question 1: Your class of 100 individuals has been typed for a 3-allele microsatellite polymorphism, and the following genotypes were obtained.

Genotype Count

1,1 4

1,2 18

1,3 24

2,2 8

2,3 28

3,3 18

Based on these genotype counts, what are the gene frequencies of alleles 1,2, and 3?

Answer: F(1) = (8 + 18 + 24)/200 = 0.25

F(2) = (18 + 16 + 28)/200 = 0.31

F (3) = (24 + 28 + 36)/200 = 0.44

Question 2: Suppose you are studying a complex multifactorial disease, and you find that the concordance rate for this trait in monozygotic twins is identical to that of dizygotic twins. What is the heritability of this disease?

Answer: 0

Question 3: A boy has severe hemophilia A (X-linked recessive). His sister also has hemophilia, but her disease is much milder. What is the most likely explanation for this difference in severity?

Answer: Sister is a manifesting heterozygote

Question 4: Women with Turner syndrome (45, X karyotype) sometimes reproduce. What is the risk of a 45, X karyotype in their offspring at conception?

Answer: 1/4

Question 5: Consider the accompanying pedigree, in which an autosomal dominant disease-causing gene is segregating. Each family member has been typed for a linked 4-allele microsatellite (recombination frequency = 0.02). What is the risk that the offspring in generation III will inherit the disease-causing gene?

Answer: 0.98

Question 6: In the accompanying pedigree, in which an autosomal recessive disease is segregating, each member has been typed for a closely linked 5-allele microsatellite polymorphism. The genotypes are shown in the autoradiogram. The disease genotype for individual 5 is shown. For individuals 6,7, and 8, indicate whether they are homozygous normal, heterozygous carrier, or homozygous affected.

Answer: 6 = Heterozygote

7 = Normal homozygote

8 = Homozygous affected

Question 7: The president of a mythical country has just been named in a paternity suit. The defendant (labeled WC in the autoradiogram), the mother (labeled ML), and the baby (labeled “Buddy”) have each been typed for two VNTR systems, as shown in the autoradiograms below. Each of these VNTR systems has four alleles. For the first VNTR, the frequencies of alleles 1,2,3, and 4 in the general population are 0.2, 0.4, 0.3, and 0.1, respectively. For the second VNTR, the frequencies of alleles 1,2,3, and 4 are 0.1, 0.1, 0.2, and 0.6, respectively. Answer 2 questions: Does the autoradiogram indicate that WC could be the father of Buddy? What is the probability that another male in the general population could be the father of Buddy?

Answer: 1) yes

2) 0.4 x 0.6 = 0.24

Question 8: In the accompanying pedigree, an autosomal dominant disease gene is being transmitted. Each family member has been typed for a 7-allele microsatellite polymorphism. Based on the genotypes in generation III, what is the recombination frequency for the disease locus and the microsatellite polymorphism?

Answer: 1/10

Question 9: A large number of different mutations in the NF1 gene can cause neurofibromatosis type 1. Although NF1 has been cloned and sequenced, indirect genetic diagnosis is often used for this disease. Why?

Answer:  Too difficult, expensive, and time-consuming to test directly for all the

different mutations.

Question 10: (essay) Describe and compare direct and indirect genetic diagnosis (use at least one disease example for each type of diagnosis). What are the advantages and disadvantages of each approach?

Answer: Indirect diagnosis refers to the use of linkage analysis to determine whether an individual has inherited a disease-causing gene from a parent. It is used when a disease gene has been mapped but not yet cloned or, in some cases, when the mutations at a locus are very numerous or poorly characterized (e.g., Marfan syndrome, cystic fibrosis in some populations). With direct diagnosis, it is possible to examine the disease-causing mutation(s) directly through methods such as allele-specific oligonucleotide hybridization, restriction site analysis, DNA sequencing, or DNA chip hybridization. Many diseases are now diagnosed directly, including sickle cell disease, alpha-1-antitrypsin deficiency, autosomal dominant breast cancer, and cystic fibrosis. Compared with indirect diagnosis, the advantages of direct diagnosis are that the mutation itself must be identified, some sequence information must be known, and large numbers of mutations can render the approach unfeasible. These disadvantages do not apply to indirect diagnosis, where the disease-causing locus need not be cloned and sequenced.