Haplotype of the C61G BRCA1 mutation in Polish and Jewish individuals

Genet Test Mol Biomarkers. 2009 Aug;13(4):465-9. doi: 10.1089/gtmb.2009.0001.

Abstract

Recurring mutations in the BRCA1 gene are noted in some populations and represent either founder mutations or a mutational hot spot. The C61G*BRCA1 (c.181T>G) missense mutation is a pathogenic one commonly reported in Polish individuals. A Jewish non-Ashkenazi family (of Italian ancestry) was found to carry this mutation, and the present study aimed at evaluating whether this mutation represents a founder mutation or a mutational hot spot. To that end, multilocus allelotyping using five markers intragenic to and flanking the BRCA1 gene spanning a genomic region of approximately 1.5 Mbp was carried out in that family and in 20 unrelated Polish C61G*BRCA1 mutation carriers. Phasing was done using affected and unaffected Jewish family members. The alleles that compose the pathogenic, mutation-carrying intragenic BRCA1 haplotype of the Jewish mutation carriers were detected in 18/20 Polish mutation carriers. The two flanking markers farthest away showed more diversity, between and even within Polish individuals. In conclusion, the *BRCA1 missense mutation is a founder mutation that can be detected in geographically related populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • BRCA1 Protein / genetics*
  • Breast Neoplasms / genetics
  • DNA Mutational Analysis
  • Female
  • Founder Effect*
  • Genes, BRCA1*
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Haplotypes*
  • Humans
  • Israel / epidemiology
  • Jews / genetics
  • Middle Aged
  • Mutation, Missense*
  • Poland / epidemiology

Substances

  • BRCA1 Protein