The 185delAG BRCA1 mutation originated before the dispersion of Jews in the diaspora and is not limited to Ashkenazim

Human Molecular Genetics
R B Bar-SadeE Friedman

Abstract

The 185delAG mutation in BRCA1 is detected in Ashkenazi Jews both in familial breast and ovarian cancer and in the general population. All tested Ashkenazi mutation carriers share the same allelic pattern at the BRCA1 locus. Our previous study showed that this 'Ashkenazi' mutation also occurs in Iraqi Jews with a similar allelic pattern. We extended our analysis to other non-Ashkenazi subsets: 354 of Moroccan origin, 200 Yemenites and 150 Iranian Jews. Heteroduplex analysis complemented by direct DNA sequencing of abnormally migrating bands were employed. Four of Moroccan origin (1. 1%) and none of the Yemenites or Iranians was a carrier of the 185delAG mutation. BRCA1 allelic patterns were determined for four of these individuals and for 12 additional non-Ashkenazi 185delAG mutation carriers who had breast/ovarian cancer. Six non-Ashkenazi individuals shared the common 'Ashkenazi haplotype', four had a closely related pattern, and the rest ( n = 6) displayed a distinct BRCA1 allelic pattern. We conclude that the 185delAG BRCA1 mutation occurs in some non-Ashkenazi populations at rates comparable with that of Ashkenazim. The majority of Jewish 185delAG mutation carriers have a common allelic pattern, supporting the founder effe...Continue Reading

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