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Age estimates of ancestral mutations causing factor VII deficiency and Dubin–Johnson syndrome in Iranian and Moroccan Jews are consistent with ancient Jewish migrations

Authors: Ronit, Mor-Cohen; Ariella, Zivelin; Yonit, Fromovich-Amit; Victoria, Kovalski; Nurit, Rosenberg; Uri, Seligsohn;

Age estimates of ancestral mutations causing factor VII deficiency and Dubin–Johnson syndrome in Iranian and Moroccan Jews are consistent with ancient Jewish migrations

Abstract

Factor VII (FVII) deficiency and Dubin-Johnson syndrome (DJS) are rare autosomal recessive disorders caused by mutations in F7 and MRP2 genes, respectively. Both disorders are relatively frequent among Iranian and Moroccan Jews. FVII deficiency in both populations is caused by a founder A244V mutation in the F7 gene and DJS is caused by two founder mutations, I1173F and R1150H in the MRP2 gene that are specific for Iranian and Moroccan Jewish patients, respectively. We estimated the age of FVII A244V and MRP2 I1173F by analysis of microsatellite markers flanking F7 and MRP2 genes, respectively, in 13 Iranian Jewish homozygotes for the I1173F mutation and 21 Iranian and Moroccan Jewish homozygotes for the A244V mutation. Dating of the mutations was estimated by the DMLE+2.0 program employing observed linkage disequilibria of multiple genetic markers. The estimated age of the I1173F mutation was approximately 1500 years, and the age of the A244V mutation was approximately 2600 years. These estimates suggest that I1173F causing DJS in Iranian Jews occurred after the separation of Iranian Jews from Moroccan Jews 2000-2600 years ago, while A244V causing FVII deficiency in Iranian and Moroccan Jews occurred prior to the divergence of these two populations.

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Keywords

Jaundice, Chronic Idiopathic, Factor VII Deficiency, Mutation, Missense, Membrane Transport Proteins, Emigration and Immigration, Factor VII, Iran, Founder Effect, Linkage Disequilibrium, Multidrug Resistance-Associated Protein 2, Time, Morocco, Jews, Mutation, Humans, Multidrug Resistance-Associated Proteins, History, Ancient, Microsatellite Repeats

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Powered by OpenAIRE graph
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
9
Average
Average
Average