Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study

Am J Hum Genet. 1996 Feb;58(2):271-80.


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 types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • BRCA1 Protein
  • Breast Neoplasms / genetics
  • Chromosome Mapping
  • Family Health
  • Female
  • Genetic Markers / genetics
  • Genotype
  • Haplotypes / genetics*
  • Humans
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Ovarian Neoplasms / genetics
  • Phenotype
  • Polymorphism, Single-Stranded Conformational
  • Transcription Factors / genetics*


  • BRCA1 Protein
  • Genetic Markers
  • Neoplasm Proteins
  • Transcription Factors