1. Problem 1 A healthy 60-year-old man (II1) presents with a history of his father having had Huntington’s disease. He has one son age 40yrs and one daughter age 35yrs who are unaffected. What is the probability he inherited Huntington’s disease? Age in yearsProbability of detectable gene expression 20.02 25.05 30.1 35.2 40.3 45.35 50.5 55.65 60.75 65.85 70.95 I II III 60 yrs 40 yrs35 yrs 1 1 12

2. Answer Problem 1 What is the probability he inherited Huntington’s disease. It is easiest to draw a chart with the prior and conditional propability Age in yearsProbability of detectable gene expression 20.02 25.05 30.1 35.2 40.3 45.35 50.5 55.65 60.75 65.85 70.95 Hypothesis 1 II-1 Is a heterozygous Hypothesis 2 II-1 Is homozygous normal Prior probability1/2 Conditional Probability II1 age 60 yrs.251 II1 age 40 yrs0.5+(0.5x0.7) =0.85 1 II2 age 35 yrs 0.5+(0.5x0.8) =0.90 1 Joint probability0.095625.5 Posterior probability 0.095625/(0.095 625+0.5)=0.16 =16% 0.5/(0.095625+0. 5)=0.84=84% I II III 60 yrs 40 yrs35 yrs 1 1 12 Did not inherit plus probability they did inherit and are not expressing it at age 40 The chance the gene is not express at 60

3. Problem 2 Type 1 diabetes affects 700,000 people in the United States and is the most common chronic metabolic disorder to affect children. It is most common in Caucasian populations, especially those in Scandinavia, and rare in people of Asian or African descent. Out of 100 people with Type 1 diabetes, 80 have no family members with the disease. The remaining 20 people have at least one family member with diabetes. Although most people in the population have a 0.4 percent chance of developing Type 1 diabetes, the risk increases to about two percent if your mother has diabetes and six percent if your father or siblings have Type 1 diabetes. If your sibling with diabetes is a fraternal twin your risk increases to 11 percent and it increases to roughly 50 percent if your identical twin has diabetes See the chart to the left. a. Does type 1 diabetes have a genetic component. Why? b. Are there nongenetic influences for type 1 diabetes. Why? c. What is one explanation for the higher incidence of inheritance from the father

4. Answer Problem 2 a. Does type 1 diabetes have a genetic component. Why? The higher incidence of the disease in family member and particularly the twin suggests a genetic component to the disease b. Are there nongenetic influences for type 1 diabetes. Why? If there were no environmental influences the twins should have 100% concordance. The fact that only 50% are affected suggests environment influences c. What is one explanation for the higher incidence of inheritance from the father? There are several explanation. One possibility is that some the genes which are involve in type 1 diabetes have a paternal imprint. Note: The DR4 allele of the HLA locus (major histocompatibility complex (MHC) HLA region on chromosome 6p21 ) appears to be related to the paternity risk

5. Problem 3 You are attempting to locate a strange disease gene known to cause square spots in cats. Previous linkage studies have suggested that the cause of square spots is approximately 80 kb from polymorphism square. Using the tools below, describe one method you might use to locate the gene. What organisms would you use. What probes would you use. Draw an illustration of your method. What is the fewest number of lambda clones you might need. Square polymorphism Cat with a case of square spots Cat lambda DNA library Restriction enzymes 80kb Some Tools you should use Subclone of square polymorphism 80kb Possible square spots gene

6. Answer Problem 3 One method to reach the square spot gene would be to do a chromosomal walk in the direction of the square spot gene starting from the square polymorphism There are multiple steps to this experiment which are repeated First you use a fragment from your square polymorphism to probe the cat lambda DNA library 80kb Possible square spots gene Cat lambda DNA library Probe library with DNA fragment from square polymorphism subclone Isolate lambda clone contain polymorphism subclone Restriction map and isolate a new subclone in the direction of the square spot gene Square spot polymorphism Probe same library with new subclone fragment Isolate lambda clone containing new subclone fragment Repeat until you reach square spot gene What organisms would you use? You would use lambda phage for the library. You might use E.coli for amplification of your subclones or PCR. What probes would you use? You would start with the a DNA probe to square polymorphism. Then you would selected probes from the lambda clones which were progressively closer to the square spots gene What is the fewest number of lambda clones you might need. Each lambda clone is about 15 kb Therefore the minimum number clones you would need is 6