The 1100delAT BRCA1 and the 8765delAG BRCA2 mutations: occurrence in high-risk non-Ashkenazi Jews and haplotype comparison of Jewish and non-Jewish carriers

• Published in: Familial cancer Vol. 3; no. 1; pp. 11 - 14
• Main Authors: Gal, Inbar, Gershoni Baruch, Ruth, Haber, Daniel, Dagan, Efrat, Eisenberg-Barzilai, Shlomit, Zidan, Jamal, Friedman, Eitan
• Format: Journal Article
• Language: English
• Published: Netherlands Springer Nature B.V 2004
• Subjects: Adult; African Continental Ancestry Group - genetics; Aged; Aged, 80 and over; Base Sequence; BRCA1 Protein - genetics; BRCA2 Protein - genetics; Breast Neoplasms - ethnology; Breast Neoplasms - genetics; Cohort Studies; Female; Genetic Predisposition to Disease; Genetic Testing; Germ-Line Mutation; Haplotypes; Heterozygote; Humans; Israel; Jews - genetics; Middle Aged; Molecular Sequence Data; Pedigree; Polymerase Chain Reaction; Risk Assessment; Israel
• ISSN: 1389-9600; 1573-7292
• DOI: 10.1023/B:FAME.0000026837.32470.b4

Few mutations have been described in BRCA1 and BRCA2 in high-risk non-Ashkenazi Jews. In a Libyan family the 1100delAT BRCA1 mutation was detected and the 8765delAG BRCA2 mutation was previously described in two Jewish-Yemenite-families. In this study, the rate of these mutations in high-risk Jews of North African and Yemenite origin was assessed, and the BRCA1 -linked haplotype of Jewish and non-Jewish 1100delAT mutation carriers were compared. Genotyping included 64 high-risk Yemenite women (tested only for the BRCA 2 mutation) and 147 high-risk North African women, tested for both mutations. PCR amplification was followed by either restriction enzyme digestion or DGGE or dHPLC analyses and direct sequencing. For haplotyping, 5 BRCA1 -linked markers were used. Neither the 1100delAT BRCA1 nor the 8765delAG BRCA2 mutations were detected in any non-Ashkenazi individual. The haplotype of the non-Jewish 1100delAG mutation carrier differed from that of the Jewish-Libyan mutation carriers. We conclude that both1100delAT BRCA1 and 8765delAG BRCA2 mutations occur rarely in high-risk non-Ashkenazi Jews, and while the latter seems to be a founder mutation in some populations, the former occurs on a different background in ethnically diverse families.