ABCMdb

PMID: 17287630

Mor-Cohen R, Zivelin A, Fromovich-Amit Y, Kovalski V, Rosenberg N, Seligsohn U
Age estimates of ancestral mutations causing factor VII deficiency and Dubin-Johnson syndrome in Iranian and Moroccan Jews are consistent with ancient Jewish migrations.
Blood Coagul Fibrinolysis. 2007 Mar;18(2):139-44., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC2 p.Arg1150His ABCC2 p.Ile1173Phe 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. Login to comment 3 ABCC2 p.Ile1173Phe ABCC2 p.Ile1173Phe 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. Login to comment 5 ABCC2 p.Ile1173Phe ABCC2 p.Ile1173Phe 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. Login to comment 19 ABCC2 p.Arg1150His ABCC2 p.Ile1173Phe We previously reported two distinct missense mutations, I1173F and R1150H, causing DJS in Iranian and Moroccan Jewish patients, respectively. Login to comment 24 ABCC2 p.Ile1173Phe In this study we addressed the question of whether an age estimate of the FVII A244V mutation would be consistent with the hypothesis that this mutation occurred before the historic separation of Moroccan from Iranian Jews, and that the MRP2 I1173F mutation causing DJS in Iranian Jews occurred after the divergence of the Iranian and Moroccan Jews. Login to comment 37 ABCC2 p.Ile1173Phe ABCC2 p.Ile1173Phe Age estimates of the MRP2 I1173F and FVII A244V mutations Estimating the age of the MRP2 I1173F mutation and the FVII A244V mutation was carried out by the DMLEþ2.0 software program (www.dmle.org). Login to comment 47 ABCC2 p.Ile1173Phe Results Figure 2a shows the frequencies of the nine microsatellitic nucleotide repeats in chromosomes of DJS patients bearing the MRP2 I1173F mutation and normal chromosomes. Login to comment 49 ABCC2 p.Ile1173Phe The differences in the allele frequencies between normal and mutants were statistically significant (P < 0.05) for all microsatellites, which is consistent with a founder effect for the I1173F mutation. Login to comment 53 ABCC2 p.Ile1173Phe The DMLEþ2.0 program was then used for estimating the age of the MRP2 I1173F mutation and the FVII A244V mutation using the microsatellite data from patients and controls. Login to comment 54 ABCC2 p.Ile1173Phe Figure 3 shows the posterior probability densities of the mutation age for the MRP2 I1173F and FVII A244V. Login to comment 55 ABCC2 p.Ile1173Phe These mutation densities depict a peak at 75 generations for MRP2 I1173F and at 129 generations for FVII A244V. Login to comment 56 ABCC2 p.Ile1173Phe Assuming 20 years for a generation, the age of the MRP2 I1173F mutation was estimated to be 1500 years (95% credible set 660-3820) and the age of the FVII A244V mutation was estimated to be 2580 years (95% credible set 1440-4840). Login to comment 67 ABCC2 p.Arg1150His ABCC2 p.Ile1173Phe We also showed that DJS is prevalent in both populations and is caused by distinct mutations, I1173F in Iranian Jews and R1150H in Moroccan Jews [17]. Login to comment 69 ABCC2 p.Ile1173Phe We investigated this assumption by estimating the age of FVII A244V and MRP2 I1173F using the DMLEþ 2.0 program. Login to comment 71 ABCC2 p.Ile1173Phe ABCC2 p.Ile1173Phe The highest probability of the estimated age of FVII A244V was approximately 2600 years and that of MRP2 I1173F was approximately 1500 years. These age estimates had wide 95% credible sets, 660-3820 years for the MRP2 I1173F mutation and 1440-4840 years for the FVII A244V mutation, respectively. Login to comment 74 ABCC2 p.Arg1150His An age estimate was not performed for the R1150H mutation due to the small number of available patients (five patients from four unrelated families). Login to comment 75 ABCC2 p.Arg1150His The fact that R1150H is a founder mutation unique for Moroccan Jews, however, indicates that it probably occurred after the separation of the two populations. Login to comment