Signatures of founder effects, admixture, and selection in the Ashkenazi Jewish population

The paper is free at the PNAS website. The raw data is available. The press release mentions:
In addition, a region on chromosome 12 showed selection in the Ashkenazi Jewish population but not Europeans. This area encompasses 18 genes but the investigators noticed that one of these, ALDH2, is important in alcohol metabolism, and genetic variation in ALDH2 has previously been shown to affect alcohol consumption, Bray says.

"This is consistent with historical and modern reports of lower alcoholism rates in Jews, although social and religious practices are also thought to play a role," he says. "However, a more detailed analysis of variants in the ALDH2 gene would be necessary to show a mechanistic link."
The abstract refers to ALDH2 as a genomic region under selection that accounts for "alcohol tolerance", but the Jewish version in fact confers alcohol intolerance:
Reduction in activity of the mitochondrial aldehyde dehydrogenase 2 (ALDH2) enzyme due to genetic deficiency causes reactions related to alcohol consumption and lowers the risk of alcoholism.
The authors suggest that the proliferation of the defective ALDH2 version among Jews may be incidental to selection on a different gene:
The mechanism driving selection of the ALDH2 locus is unknown, but a plausible target of selection also within this selected region is the TRAFD1/FLN29 gene, which is a negative regulator of the innate immune system, important for controlling the response to bacterial and viral infection (49). TRAFD1/FLN29 may have conferred a selective advantage in the immune response to a pathogen, perhaps near the time that the Jews returned to Israel from their Babylonian captivity. Despite the unclear selective mechanism, this remains a remarkable example of a putatively selected region accounting for a known population phenotype.
Reference: Bray et al. Signatures of founder effects, admixture, and selection in the Ashkenazi Jewish population. PNAS. Published online before print August 26, 2010, doi: 10.1073/pnas.1004381107


Rob S. said...

I reckon they mean, a group or individual tolerance to being around and drinking alcohol without developing the 'bad reaction' of alcoholism. Scientists love to express themselves poorly.

Rob S. said...

Oh, nevermind. Actually they probably mean that that *locus* controls tolerance (meaning, relative tolerance or intolerance). Due to the different alleles that occur at the locus.

I notice that they are suggesting that the linked allele linked in Ashkenazim causes a relative increase in immune aggressiveness. That could certainly happen when a serious new pathogen shows up, but Cochran and Harpending in a 2009 paper suggested that the immune system is generally tuned down outside Africa (and especially in the New World).

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