Problem 1. Genetic linkage studies can be either based on a model of inheritance or parameter-free. For the former, one needs to know the mode of inheritance and the penetrance (age-risk function). How are penetrance values obtained for presumed genetic susceptibility?
Problem 2. Twelve families are selected for a genetic linkage study because of a high prevalence of disease. A genome screen is performed, using anonymous DNA markers on all autosomes. Significant evidence is observed for linkage to a marker on chromosome 2 (D2S123) in four families. The LOD score for the remaining families at this locus is significantly negative. How do you interpret this finding?