Haplotype analysis and ancient origin of the BRCA1 c.4035delA Baltic founder mutation

Eur J Med Genet. 2013 Mar;56(3):125-30. doi: 10.1016/j.ejmg.2012.12.007. Epub 2012 Dec 27.

Abstract

Uncertainty exists about the origin of BRCA1 c.4035delA mutation which is prevalent in Baltic countries, with the highest frequency being in Lithuania (53% of all BRCA1 mutations), although formal founder mutation analysis by haplotype has not yet been undertaken. In this study we genotyped 78 unrelated BRCA1 c.4035delA mutation carriers families from Lithuania, Latvia, Poland and Russia. The results from the haplotype analyses were used to estimate the age of the mutation. Using maximum likelihood methods we estimated that the mutation arose approximately 1550 years (62 generations of 25 years) ago (ca. 5th century) somewhere in the present territory of Lithuania, in the area inhabited by ancient Baltic tribes at that time. Our results show that this mutation gradually entered the gene pool in the neighboring countries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cluster Analysis
  • Founder Effect*
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Haplotypes*
  • Humans
  • Latvia
  • Likelihood Functions
  • Lithuania
  • Mutation
  • Poland
  • Russia
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • Genetic Markers
  • BRAP protein, human
  • Ubiquitin-Protein Ligases