Before embarking on large and expensive studies to identify genetic loci that underlie breast cancer susceptibility or that modify the penetrance in Ashkenazi BRCA1/2 mutation carriers, we propose a preliminary evaluation of linkage disequilibrium (LD) in this population. The primary context for this LD study will be the known founder BRCA1 mutation 185delAG, present in approximately 1 in 20 Ashkenazi Jewish women with breast cancer and in 1 in 100 Ashkenazi Jews in general. By typing a dense set of single nucleotide polymorphisms (SNP) and short tandem repeat polymorphisms (STRP) around these mutations, we will determine the patterns and extent of LD in order to address the question of whether this founder BRCA1 mutation could have been identified in a case-control association study with markers at varying density. This information will also help determine the feasibility of performing a genome-wide SNP scan to identify loci that influence breast cancer susceptibility, particularly in the context of the International HaplotypeMap effort.
|Struewing, Jeffery P (2004) Genomic approaches to identifying breast cancer susceptibility factors. Breast Dis 19:3-9|