title: Haplotype analysis of the 185delAG BRCA1 mutation in ethnically diverse populations.
abstract: The 185delAG* BRCA1 mutation is encountered primarily in Jewish Ashkenazi and Iraqi individuals, and sporadically in non-Jews. Previous studies estimated that this is a founder mutation in Jewish mutation carriers that arose before the dispersion of Jews in the Diaspora ~2500 years ago. The aim of this study was to assess the haplotype in ethnically diverse 185delAG* BRCA1 mutation carriers, and to estimate the age at which the mutation arose. Ethnically diverse Jewish and non-Jewish 185delAG*BRCA1 mutation carriers and their relatives were genotyped using 15 microsatellite markers and three SNPs spanning 12.5 MB, encompassing the BRCA1 gene locus. Estimation of mutation age was based on a subset of 11 markers spanning a region of ~5 MB, using a previously developed algorithm applying the maximum likelihood method. Overall, 188 participants (154 carriers and 34 noncarriers) from 115 families were included: Ashkenazi, Iraq, Kuchin-Indians, Syria, Turkey, Iran, Tunisia, Bulgaria, non-Jewish English, non-Jewish Malaysian, and Hispanics. Haplotype analysis indicated that the 185delAG mutation arose 750-1500 years ago. In Ashkenazim, it is a founder mutation that arose 61 generations ago, and with a small group of founder mutations was introduced into the Hispanic population (conversos) ~650 years ago, and into the Iraqi-Jewish community ~450 years ago. The 185delAG mutation in the non-Jewish populations in Malaysia and the UK arose at least twice independently. We conclude that the 185delAG* BRCA1 mutation resides on a common haplotype among Ashkenazi Jews, and arose about 61 generations ago and arose independently at least twice in non-Jews.
authors: The Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors: Yael
authors: Y
authors: Laitman
authors: Bing-Jian
authors: BJ
authors: Feng
authors: Itay M
authors: IM
authors: Zamir
authors: Jeffrey N
authors: JN
authors: Weitzel
authors: Paul
authors: P
authors: Duncan
authors: Danielle
authors: D
authors: Port
authors: Eswary
authors: E
authors: Thirthagiri
authors: Soo-Hwang
authors: SH
authors: Teo
authors: Gareth
authors: G
authors: Evans
authors: Ayse
authors: A
authors: Latif
authors: William G
authors: WG
authors: Newman
authors: Ruth
authors: R
authors: Gershoni-Baruch
authors: Jamal
authors: J
authors: Zidan
authors: Shani
authors: S
authors: Shimon-Paluch
authors: David
authors: D
authors: Goldgar
authors: Eitan
authors: E
authors: Friedman
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D018703:Founder Effect; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D007585:Jews / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human