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

The 185delAG mutation in BRCA1 is detected in Ashkenazi Jews both infamilial breast and ovarian cancer and in the general population. Alltested Ashkenazi mutation carriers share the same allelic pattern at theBRCA1 locus. Our previous study showed that this 'Ashkenazi' mutation alsooccurs in Iraqi Jews with a similar allelic pattern. We extended ouranalysis to other non-Ashkenazi subsets: 354 of Moroccan origin, 200Yemenites and 150 Iranian Jews. Heteroduplex analysis complemented bydirect DNA sequencing of abnormally migrating bands were employed. Four ofMoroccan origin (1. 1%) and none of the Yemenites or Iranians was a carrierof the 185delAG mutation. BRCA1 allelic patterns were determined for fourof these individuals and for 12 additional non-Ashkenazi 185delAG mutationcarriers who had breast/ovarian cancer. Six non-Ashkenazi individualsshared the common 'Ashkenazi haplotype', four had a closely relatedpattern, and the rest ( n = 6) displayed a distinct BRCA1 allelic pattern.We conclude that the 185delAG BRCA1 mutation occurs in some non-Ashkenazipopulations at rates comparable with that of Ashkenazim. The majority ofJewish 185delAG mutation carriers have a common allelic pattern, supportingthe founder effect notion, but dating the mutation's origin to an earlierdate than currently estimated. However, the different allelic pattern atthe BRCA1 locus even in some Jewish mutation carriers, might suggest thatthe mutation arose independently.