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BRCA1:185delAG found in the San Luis Valley probably originated in a Jewish founder
  1. I Makriyianni1,
  2. N Hamel2,
  3. S Ward4,
  4. W D Foulkes3,
  5. S Graw5
  1. 1Department of Human Genetics, McGill University, Montreal, Quebec, Canada
  2. 2Department of Medicine, McGill University Health Centre, Montreal
  3. 3Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University
  4. 4University of Wyoming, Laramie, Wyoming, USA
  5. 5Eleanor Roosevelt Institute, University of Denver, Denver, Colorado, USA
  1. Correspondence to:
 Dr William D Foulkes
 Montreal General Hospital, 1650 Cedar Avenue, Room L10-116, Montreal, Quebec, Canada H3G 1A4;

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Three BRCA1/2 mutations (185delAG and 5382insC in BRCA1, and 617delT in BRCA2) are present in about 2.5% of the Ashkenazi Jewish population,1–4 and in 10–12% of Ashkenazi Jewish women with breast cancer.5 Mutations that become common in a population are often explained by the presence of a “founder effect”. This effect tends to exist when a population is established by a small group of ancestors. The members of the group are called founders and become isolated from the original population from which they are derived on account of geographical, cultural, or linguistic barriers. If this isolation persists, genetic drift can cause disease producing alleles present in the founders to become more frequent in subsequent generations.

The San Luis Valley (SLV) is a large, isolated valley situated on the border between New Mexico and Colorado. The first settlers were Spaniards of the de Oñate expedition in 1598, but today it has an admixed population descended from Native Americans, West Africans, and Europeans.6 A previous study in Colorado of breast cancer patients with SLV ancestry revealed the presence of a hereditary breast cancer mutation, BRCA1:185delAG.7 Many of these individuals came from areas of Spanish settlement in what is now northern New Mexico, an area known to have had a number of Spanish settlers with Jewish heritage. This population remained fairly coherent until the mid-1900s, which would have allowed the fixation of certain mutations in the population through the founder effect.8

The 185delAG mutation (c.68_69del2) is a founder mutation in the Ashkenazi Jewish population and is the most common BRCA1 mutation in this population, with a frequency of 1%.2,3 Markers flanking this mutation have conserved alleles among Ashkenazi carriers, allowing for the construction of a distinct, linked haplotype.4 In this …

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  • Competing interests: none declared