Over-representation of two specific haplotypes among chromosomes harbouring BRCA1 mutations

Eur J Hum Genet. 2003 Jun;11(6):489-92. doi: 10.1038/sj.ejhg.5200969.


The BRCA1 gene is included in a 200-400 kb region that is subjected to a recombination suppression mechanism; this region shows nearly complete linkage disequilibrium for a series of common biallelic polymorphisms, all of them with rarer allele frequency close to 0.4. These series of SNPs define two major haplotypes designated as class I and class II. In the present study, we have determined haplotype classes in the index case of 106 breast/ovarian cancer families previously screened for mutations in the BRCA genes and we have found that haplotype II (the less frequent in the control population) is over-represented among chromosomes harbouring mutations in BRCA1. In addition, we have defined a subtype of chromosomes characterized by haplotype I and one specific allele for the microsatellite marker D17S855, which are also more frequently associated with BRCA1 mutations. These findings may have important consequences for the selection of families with higher probabilities of carrying mutations in the BRCA1 gene.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Frequency / genetics*
  • Genes, BRCA1*
  • Haplotypes / genetics*
  • Humans
  • Linkage Disequilibrium
  • Microsatellite Repeats / genetics
  • Polymorphism, Single Nucleotide / genetics*