Linkage Disequilibrium between the FES, D/5S/27, and BLM Loci in Ashkenazi Jews with Bloom Syndrome

Bloom syndrome (BS) is more common in the Ashkenazi Jewish than in any other population. Approximately 1 in 110 Ashkenazi Jews carries blm, the BS mutation. The locus mutated in BS, BLM, maps to chromosome subband 15q26.1, tightly linked to the proto-oncogene FES. We have investigated the basis for the increased frequency of blm in the Ashkenazim by genotyping polymorphic microsatellite loci tightly linked to BLM in affected and unaffected individuals from Ashkenazi Jewish and non-Ashkenazi populations. A striking association of the C3 allele at FES with blm (Δ = .422; p = 5.52 × 10⁷) and of the 145-bp and 147-bp alleles at D15S127 with blm (Δ = .392 and Δ = .483, respectively; p = 2.8 × 10^-5 and p = 5.4 × 10^-7, respectively) was detected in Ashkenazi Jews with BS. This linkage disequilibrium constitutes strong support for a founder-effect hypothesis: the chromosome in the hypothetical founder who carried blm also carried the C3 allele at FES and either the 145-bp or the 147-bp allele at D15S127.