Analysis of genetic linkage and somatic loss of heterozygosity in affected pairs of first-degree relatives


Recently, data on loss of constitutional heterozygosity (LOH) have been used by several groups to increase the power to detect linkage in pedigrees with an inherited cancer predisposition. This approach assumes that the predisposition is due to the inheritance of the defective copy of a tumor suppressor. In order to assess the gain of power expected from the inclusion of LOH data, we simulated segregation and somatic loss of alleles in pedigrees consisting of an affected pair of first-degree relatives. We explored the effects of pedigree structure, frequency of loss, penetrance, and recombination rate on the expected LOD score. The results indicate that, for establishment of genetic linkage, isolated parent-offspring pairs can be as informative as sib pairs and that they could represent an additional source of information in linkage studies.

American Journal of Human Genetics 1997; 61(2):418-422