Linkage Analysis of Sibling Pairs in Cancer

Abstract

The main goal of this project is to identify mutations within genes that will increase cancer risk. Once these mutations have been identified, the population can be screened mutations and a cancer risk profile can be calculated for each individual. Furthermore, the biochemistry and mechanism of action of the mutant allele may be further studied to gain understanding of its role in pathways relevant to cancer. This particular project will use genetic linkage analysis to help identify these mutations. Due to the late age of onset (for cancers such as breast and prostate), it is unlikely that parents and grandparents are available for sampling (genotypes cannot be determined). Without these genotypes, the origin of the alleles cannot be ascertained. Affected Sib Pairs (ASP) offer an alternative approach to traditional linkage analysis (pedigrees). In this study, the ASP patients are full blood brothers/sisters that have prostate/breast cancer respectively. ASP analysis is based on the hypothesis that siblings share half their genes (null hypothesis). Our alternative hypothesis is that siblings will share more than what is expected. If the alternative hypothesis is true, this gives us evidence for linkage. Linkage between the microsatellite marker and candidate gene is highly suggestive that a mutation may be present in our candidate gene. Candidate genes are chosen that are known to be involved in cellular processes relevant to cancer (ex.- genes involved in cell cycle; p53 gene - apoptosis). Microsatellite markers near the candidate genes are selected to genotype the sib pairs.