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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Han, Yi Osier, Michael V. Gu, Sheng Kidd, Judith R. Oota, Hiroki Pakstis, Andrew J. Speed, William C. Kidd, Kenneth K. |
| Description | Country affiliation: United States Author Affiliation: Han Y ( Department of Genetics, School of Medicine, Yale University, New Haven, CT 06510, USA.) |
| Abstract | The alcohol dehydrogenase (ADH) family of enzymes catalyzes the reversible oxidation of alcohol to acetaldehyde. Seven ADH genes exist in a segment of ~370 kb on 4q21. Products of the three class I ADH genes that share 95% sequence identity are believed to play the major role in the first step of ethanol metabolism. Because the common belief that selection has operated at the ADH1B*47His allele in East Asian populations lacks direct biological or statistical evidence, we used genomic data to test the hypothesis. Data consisted of 54 single-nucleotide polymorphisms (SNPs) across the ADH clusters in a global sampling of 42 populations. Both the F(st) statistic and the long-range haplotype (LRH) test provided positive evidence of selection in several East Asian populations. The ADH1B Arg47His functional polymorphism has the highest F(st) of the 54 SNPs in the ADH cluster, and it is significantly above the mean F(st) of 382 presumably neutral sites tested on the same 42 population samples. The LRH test that uses cores including that site and extending on both sides also gives significant evidence of positive selection in some East Asian populations for a specific haplotype carrying the ADH1B*47His allele. Interestingly, this haplotype is present at a high frequency in only some East Asian populations, whereas the specific allele also exists in other East Asian populations and in the Near East and Europe but does not show evidence of selection with use of the LRH test. Although the ADH1B*47His allele conveys a well-confirmed protection against alcoholism, that modern phenotypic manifestation does not easily translate into a positive selective force, and the nature of that selective force, in the past and/or currently, remains speculative. |
| ISSN | 00029297 |
| e-ISSN | 15376605 |
| Journal | The American Journal of Human Genetics |
| Issue Number | 3 |
| Volume Number | 80 |
| Language | English |
| Publisher | Cell Press (on behalf of American Society of Human Genetics) |
| Publisher Date | 2007-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Alcohol Dehydrogenase Genetics Genetics, Population Haplotypes Polymorphism, Single Nucleotide Selection, Genetic Cluster Analysis Ethanol Metabolism Gene Frequency Genotype Geography Linkage Disequilibrium Multigene Family Phylogeny Research Support, N.i.h., Extramural Research Support, U.s. Gov't, Non-p.h.s. Discipline Human Genetics |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Genetics (clinical) |
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