Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: Results of an international study Academic Article uri icon


MeSH Major

  • Haplotypes
  • Mutation
  • Neoplasm Proteins
  • Transcription Factors


  • Several BRCA1 mutations have now been found to occur in geographically diverse breast and ovarian cancer families. To investigate mutation origin and mutation-specific phenotypes due to BRCA1, we constructed a haplotype of nine polymorphic markers within or immediately flanking the BRCA1 locus in a set of 61 breast/ovarian cancer families selected for having one of six recurrent BRCA1 mutations. Tests of both mutations and family-specific differences in age at diagnosis were not significant. A comparison of the six mutations in the relative proportions of cases of breast and ovarian cancer was suggestive of an effect (P = .069), with 57% of women presumed affected because of the 1294 del 40 BRCA1 mutation having ovarian cancer, compared with 14% of affected women with the splice-site mutation in intron 5 of BRCA1. For the BRCA1 mutations studied here, the individual mutations are estimated to have arisen 9-170 generations ago. In general, a high degree of haplotype conservation across the region was observed, with haplotype differences most often due to mutations in the short-tandem-repeat markers, although some likely instances of recombination also were observed. For several of the instances, there was evidence for multiple, independent, BRCA1 mutational events.

publication date

  • February 8, 1996



  • Academic Article



  • eng

PubMed Central ID

  • PMC1914544

PubMed ID

  • 8571953

Additional Document Info

start page

  • 271

end page

  • 80


  • 58


  • 2