The evolution and population genetics of the ALDH2 locus: random genetic drift, selection, and low levels of recombination

Abstract

SummaryThe catalytic deficiency of human aldehyde dehydrogenase 2 (ALDH2) is caused by a nucleotide substitution (G1510A; Glu487Lys) in exon 12 of the ALDH2 locus. This SNP, and four non-coding SNPs, including one in the promoter, span 40 kb of ALDH2; these and one downstream STRP have been tested in 37 worldwide populations. Only four major SNP-defined haplotypes account for almost all chromosomes in all populations. A fifth haplotype harbours the functional variant and is only found in East Asians. Though the SNPs showed virtually no historic recombination, LD values are quite variable because of varying haplotype frequencies, demonstrating that LD is a statistical abstraction and not a fundamental aspect of the genome, and is not a function solely of recombination. Among populations, different sets of tagging SNPs, sometimes not overlapping, can be required to identify the common haplotypes. Thus, solely because haplotype frequencies vary, there is no common minimum set of tagging SNPs globally applicable. The F st values of the promoter region SNP and the functional SNP were about two S.D. above the mean for a reference distribution of 117 autosomal biallelic markers. These high F st values may indicate selection has operated at these or very tightly linked sites.

Genetic Association between Aldehyde Dehydrogenase 2 (ALDH2) Variation and High-Density Lipoprotein Cholesterol (HDL-C) Among Non-Drinkers in Two Large Population Samples in Japan

“…The present study confirmed that no variants of ALDH2 were detectable in the Caucasian population described in a previous study 33) . It is noteworthy that the Glu487Lys variant is almost exclusively present in East Asians, but its selective presence is puzzling.…”

dbQSNP: A database of SNPs in human promoter regions with allele frequency information determined by single-strand conformation polymorphism-based methods

“…5). the SNP (rs886205) in exon 1 of the ALDH2 gene (F ST =0.500 in our calculation), which is known to have significantly different allele frequencies between Asians and Caucasians, probably because of natural selection [Oota et al, 2004]. At least part of the high-F ST SNPs we found here should also be in the loci under selection during local adaptation.…”

“…Some characteristics of the regions with respect to SNP density and spectrum of base changes have been observed. Comparisons of allele frequencies in this database and those in the public databases revealed that frequencies can differ widely between ethnic groups, possibly as a result of differential selection, as in the case of the aldehyde dehydrogenase 2 (ALDH2; MIM# 100650) (Oota et al, 2004).…”

Rates of nausea and vomiting in pregnancy and dietary characteristics across populations

“…Recent evidence suggests population variation in expression of genes coding for alcohol dehydrogenase and aldehyde dehydrogenase, enzymes involved in alcohol metabolism. Unique alleles and haplotypes occur in East Asians, which, after alcohol consumption, lead to characteristically high levels of toxic acetaldehyde and facial flushing (Oota et al 2004). It might therefore be expected that the power of alcohol to evoke NVP is particularly marked in East Asian populations.…”