The Tyr978X BRCA1 mutation: occurrence in non-Jewish Iranians and haplotype in French-Canadian and non-Ashkenazi Jews.
BACKGROUND
The Tyr978X BRCA1 mutation is a founder mutation detected in high-risk Iraqi-Iranian Jewish families as well as in the general non-Ashkenazi population. The same mutation was also reported in non-Jewish high-risk women from Canada. Its occurrence in non-Jewish individuals from Iran has never been tested.


OBJECTIVE
Assess the occurrence rate of Tyr978X BRCA1 germline mutation in the general population of Iranian non- Jewish individuals and compare the BRCA1-linked haplotype of Jewish and non-Jewish mutation carriers.


METHODS
PCR amplification of the relevant fragment of the BRCA1 gene, followed by restriction enzyme digestion that differentiates wild type from mutant allele. For haplotyping, 7 BRCA1-linked markers were used. The tested population included 442 apparently healthy Iranian non-Jewish individuals, and 17 mutation carriers from Israel and Canada.


RESULTS
The Tyr978X BRCA1 mutation was not detected in any Iranian non-Jewish individual. The intragenic haplotype of all Jewish Israeli mutation carriers was identical, but differed from that of Canadian non-Jews in two intragenic markers.


CONCLUSIONS
The Tyr978X BRCA1 mutation which is a founder mutation in Jews, may be a hot spot in non-Jewish high risk women, and probably does not represent a rare sequence variant in Iranian non-Jews.
Quintana-Murci
Lluís
L
Laboratoire de Reproduction, Fertilite' et Populations, Institut Pasteur, Paris, France.
Gal
Inbar
I
Bakhan
Tangiz
T
Quach
Hélène
H
Sayar
S Hamid
SH
Shiri-Sverdlov
Ronit
R
Baruch
Ruth Gershoni
RG
McElreavey
Ken
K
Dagan
Efrat
E
Narod
Steven
S
Friedman
Eitan
E
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics; D002170:Canada / Q000453:epidemiology; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D005602:France / Q000208:ethnology; D019398:Genes, BRCA1; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D007492:Iran / Q000453:epidemiology; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics; D012307:Risk Factors