Human Genetics doi:10.1007/s00439-010-0846-z
An ancient autosomal haplotype bearing a rare achromatopsia-causing founder mutation is shared among Arab Muslims and Oriental Jews
Lina Zelinger et al.
Numerous cultural aspects, mainly based on historical records, suggest a common origin of the Middle-Eastern Arab Muslim and Jewish populations. This is supported, to some extent, by Y-chromosome haplogroup analysis of Middle-Eastern and European samples. Up to date, no genomic regions that are shared among Arab Muslim and Jewish chromosomes and are unique to these populations have been reported. Here, we report of a rare achromatopsia-causing CNGA3 mutation (c.1585G>A) presents in both Arab Muslim and Oriental Jewish patients. A haplotype analysis of c.1585G>A-bearing chromosomes from Middle Eastern and European origins revealed a shared Muslim–Jewish haplotype, which is different from those detected in European patients, indicating a recurrent mutation stratified by a Jewish–Muslim founder effect. Comprehensive whole-genome haplotype analysis using 250 K single nucleotide polymorphism arrays revealed a large homozygous region of ~11 Mbp shared by both Arab Muslim and Oriental Jewish chromosomes. A subsequent microsatellite analysis of a 21.5 cM interval including CNGA3 and the adjacent chromosome 2 centromere revealed a unique and extremely rare haplotype associated with the c.1585G>A mutation. The age of the shared c.1585G>A mutation was calculated using the microsatellite genotyping data to be about 200 generations ago. A similar analysis of mutation age based on the Arab Muslim data alone showed that the mutation was unlikely to be the product of a recent gene flow event. The data present here demonstrate a large (11 Mbp) genomic region that is likely to originate from an ancient common ancestor of Middle-Eastern Arab Muslims and Jews who lived approximately 5,000 years ago.
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The age of the shared c.1585G>A mutation was calculated using the microsatellite genotyping data to be about 200 generations ago. A similar analysis of mutation age based on the Arab Muslim data alone showed that the mutation was unlikely to be the product of a recent gene flow event. The data present here demonstrate a large (11 Mbp) genomic region that is likely to originate from an ancient common ancestor of Middle-Eastern Arab Muslims and Jews who lived approximately 5,000 years ago.
How exactly do they calculate mutation ages and how reliable are these calculations?
Ponto,
Based on the common understanding of what Mizrahi Jews means, it would include Iranian and Iraqi Jews, as well as Yemeni and others.
My take on this is that it suggests a common origin for ALL Mizrahi and Arabs - but not for Sephardi and Ashkenazi Jews - if that is the case, then it is highly relevant - for it would suggest Jews by conversion for these last two groups.
Interesting. From a biblical point of view, that would fit relatively nicely with Abraham being the father of both. (Assuming Abraham was a factual figure and that he lived sometime between 4000-5000 years ago)
The CNGB3 achromatopsia gene has been found in the Western Pacific, and thus, presumably would been present in the Southern Route Out of Africa population or evolved independently at a later date (although introgression of the Near Eastern allele into populations of Austronesian sea farers whose travels connected them to East Africa and Madagascar by 1000 CE would be another possible link).
I don't know how similar CNGB3 and CNGA3 (the version found in the Near Eastern populations) are, and thus whether there is any likelihood that they have a common genetic ancestor or are independent mutations. An origin for CNGA3 that is 5,000 years ago (or for that matter any time within the last 25,000 years or so), would be suggestive of an independent mutation.
While mutation rate dating isn't terribly accurate, I don't think that most people familiar with population genetics disagree that it has some meaning. I'd be curious to know if Dienekes, a strong critic of mutation rate dating as currently used, would agree that even if the date is wrong, that the CNGA3 mutation is less than 25,000 years old.
Both traits are autosomal recessive and are rare in most populations (small island populations have seen achromatopsia at 6% rates or more due to founder effects).
More details on the genetic patterns of achromatopsia generally are here. There seems to be a fair amount of variation in the specific mutations of CNGB3 that give rise to the phenotype, although one is most common in Dutch and German patients.
In CNGA3, there are 40 different mutations, although four of those mutations account for a plurality of cases.
Researchers in Pakistan revealed one family with each of the two major genes.
Interestingly, a reanalysis of data in 2007 determined that the most common achromatopsia mutation was also present in all of the sixteen cases where another gene originally thought to have been a cause and then ruled out was present.
Because of the simple inheritance pattern and the fact that most cases are caused by a single mutation, achromatopsia has been one of the first targets of gene therapy research (successful in mouse models and in human models in a similar condition), that could eventually be used in a wide variety of single mutation disease treatments.
Some single mutations conditions which have complex presentation but simple causes include the most common form of learning disability in reading, and the main gene involved in emotional vulnerability to bullying and child abuse.
Can someone having access to the full article or the figures and tables send their links?
A catalog by the Israeli Ministry of Health might help here.
Page 33 states "The missense mutation c.1585G>A, V529M was found in Oriental Jewish families from Iraq, Iran, Buchara, and Afghanistan. The frequency of the mutation in those populations is unknown". One of the references is "Sharon D, Bida L, Greenberg A, Blumenfeld A, Merin S, Rosenmann A, Banin E. A
missense CNGA3 mutation which is rare in Western populations is frequent among
both Muslim and Oriental Jewish patients with achromatopsia". So this is probably the same study?
Interestingly, It also states:
"Epidemiology:
A relatively high incidence of total color blindness was observed among Jews from
Iran and Iraq as well as among Moroccan Jews". I wonder if the anyone checked what type of mutation Moroccan Jews have...
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