Linkage disequilibrium between BLM, FES, D15S127, and IP15M9 in Ashkenazi Jews with Bloom`s syndrome (BS)
- New York Blood Center, NY (United States); and others
BS is more common in the Ashkenazi Jewish than in any other population. About 1 in 110 Ashkenazi Jews carries bbm, a BS mutation. The locus mutated in BS, BLM, maps to chromosome sub-band 15q26.1, tightly linked to the proto-oncogene FES. We have investigated the basis for the increased frequency of bbm 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 linkage disequilibrium has been observed between BLM and FES, D15S127, and IP15M9 -- three loci unseparated by conventional pedigree analysis. The linkage disequilibrium constitutes strong support for a founder-effect hypothesis. We have also analyzed blm and BLM haplotypes when genotype information from the parents was available. The haplotype analysis indicates that the chromosome in the hypothetical founder carried the C3 allele at FES, either the 145 bp or the 147 bp allele at D15S127, and the 83 bp allele at IP15M9. Besides providing strong support for the founder-effect hypothesis, haplotype analysis in a fetus at risk for BS also provided evidence against either homozygosity or heterozygosity for mutation at BLM -- evidence shown valuable by the subsequent birth of a normal boy to a couple, the father being Ashkenazi Jewish and the mother being Sephardi-Egyptian Jewish.
- OSTI ID:
- 133897
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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