BRCA1 MAPS PROXIMAL TO D17S579 ON CHROMOSOME-17Q21 BY GENETIC-ANALYSIS

Previous studies have demonstrated linkage between early-onset breast cancer and ovarian cancer and genetic markers on chromosome 17q21. The se markers define the location of a gene (BRCA1) which appears to be i nherited as an autosomal dominant susceptibility allele. We analyzed f ive families with multiple affected individuals for evidence of linkag e to the BRCA1 region. Two of the five families appear to be linked to BRCA1. One apparently linked family contains critical recombinants, s uggesting that the gene is proximal to the marker D17S579 (Mfd188). Th ese findings are consistent with the maximum-likelihood position estim ated by the Breast Cancer Linkage Consortium and with recombination ev ents detected in other linked families. Linkage analysis was greatly a ided by PCR-based analysis of paraffin-embedded normal breast tissue f rom deceased family members, demonstrating the feasibility and importa nce of this approach. One of the two families with evidence of linkage between breast cancer and genetic markers flanking BRCA1 represents t he first such family of African-American descent to be reported in det ail.