TY - JOUR
T1 - The two common mutations causing factor XI deficiency in Jews stem from distinct founders
T2 - One of ancient Middle Eastern origin and another of more recent European origin
AU - Peretz, Hava
AU - Mulai, Avital
AU - Usher, Sali
AU - Zivelin, Ariella
AU - Segal, Avihai
AU - Weisman, Zahavi
AU - Mittelman, Moshe
AU - Lupo, Hannah
AU - Lanir, Naomi
AU - Brenner, Benjamin
AU - Shpilberg, Ofer
AU - Seligsohn, Uri
PY - 1997/10/1
Y1 - 1997/10/1
N2 - Previous studies showed that factor XI (FXI) deficiency commonly observed in Ashkenazi Jews is caused by two similarly frequent mutations, type II (Glu117stop) and type III (Phe283Leu) with allele frequencies of 6.0217 and 0.0254, respectively. In Iraqi Jews, who represent the ancient gene pool of Jews, only the type II mutation was observed with an allele frequency of 0.0167. In this study we sought founder effects for each mutation by examination of four FXI gene polymorphisms enabling haplotype analysis in affected Jewish patients of Ashkenazi, Iraqi, and other origins and in Arab patients. Initial population surveys of 387 Middle Eastern Jews (excluding Iraqi Jews), 560 North African/Sephardic Jews, and 382 Arabs revealed allele frequencies for the type II mutation of 0.0026, 0.0027, and 0.0665, respectively. In contrast, the type III mutation was not detected in any of these populations. All 66 independent chromosomes bearing the type III mutation were solely observed in Ashkenazi Jewish patients and were characterized by a relatively rare haplotype. All 103 independent chromosomes bearing the type II mutation in patients of Ashkenazi, Iraqi, Yemenite, Syrian, and Moroccan Jewish origin and of Arab origin were characterized by another distinct haplotype that was rare among normal Ashkenazi Jewish, Iraqi Jewish, and Arab chromosomes. These findings constitute the first example of a mutation common to Ashkenazi Jews, non-Ashkenazi Jews, and Arabs and are consistent with the origin of type II mutation in a founder before the divergence of the major segments of Jews. Our findings also indicate that the type III mutation arose more recently in an Ashkenazi Jewish individual.
AB - Previous studies showed that factor XI (FXI) deficiency commonly observed in Ashkenazi Jews is caused by two similarly frequent mutations, type II (Glu117stop) and type III (Phe283Leu) with allele frequencies of 6.0217 and 0.0254, respectively. In Iraqi Jews, who represent the ancient gene pool of Jews, only the type II mutation was observed with an allele frequency of 0.0167. In this study we sought founder effects for each mutation by examination of four FXI gene polymorphisms enabling haplotype analysis in affected Jewish patients of Ashkenazi, Iraqi, and other origins and in Arab patients. Initial population surveys of 387 Middle Eastern Jews (excluding Iraqi Jews), 560 North African/Sephardic Jews, and 382 Arabs revealed allele frequencies for the type II mutation of 0.0026, 0.0027, and 0.0665, respectively. In contrast, the type III mutation was not detected in any of these populations. All 66 independent chromosomes bearing the type III mutation were solely observed in Ashkenazi Jewish patients and were characterized by a relatively rare haplotype. All 103 independent chromosomes bearing the type II mutation in patients of Ashkenazi, Iraqi, Yemenite, Syrian, and Moroccan Jewish origin and of Arab origin were characterized by another distinct haplotype that was rare among normal Ashkenazi Jewish, Iraqi Jewish, and Arab chromosomes. These findings constitute the first example of a mutation common to Ashkenazi Jews, non-Ashkenazi Jews, and Arabs and are consistent with the origin of type II mutation in a founder before the divergence of the major segments of Jews. Our findings also indicate that the type III mutation arose more recently in an Ashkenazi Jewish individual.
UR - http://www.scopus.com/inward/record.url?scp=0030755267&partnerID=8YFLogxK
U2 - 10.1182/blood.v90.7.2654.2654_2654_2659
DO - 10.1182/blood.v90.7.2654.2654_2654_2659
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C2 - 9326232
AN - SCOPUS:0030755267
SN - 0006-4971
VL - 90
SP - 2654
EP - 2659
JO - Blood
JF - Blood
IS - 7
ER -