A global perspective on genetic variation at the ADH genes reveals unusual patterns of linkage disequilibrium and diversity

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dc.contributor.author Osier, Michael en_US
dc.contributor.author Pakstis, Andrew en_US
dc.contributor.author Soodyall, Himla en_US
dc.contributor.author Comas, David en_US
dc.contributor.author Goldman, David en_US
dc.contributor.author Odunsi, Adekunle en_US
dc.contributor.author Okonofua, Friday en_US
dc.contributor.author Parnas, Josef en_US
dc.contributor.author Schulz, Leslie en_US
dc.contributor.author Bertranpetit, Jaume en_US
dc.contributor.author Bonne-Tamir, Batsheva en_US
dc.contributor.author Lu, Ru-Band en_US
dc.contributor.author Kidd, Judith en_US
dc.contributor.author Kidd, Kenneth en_US
dc.date.accessioned 2006-08-22T16:25:48Z en_US
dc.date.available 2006-08-22T16:25:48Z en_US
dc.date.issued 2002-07 en_US
dc.identifier.citation American Journal of Human Genetics 71N1 (2002) 84-99 en_US
dc.identifier.issn 0002-9297 en_US
dc.identifier.uri http://hdl.handle.net/1850/2423 en_US
dc.description.abstract Variants of different Class I alcohol dehydrogenase (ADH) genes have been shown to be associated with an effect that is protective against alcoholism. Previous work from our laboratory has shown that the two sites showing the association are in linkage disequilibrium and has identified the ADH1B Arg47His site as causative, with the ADH1C Ile349Val site showing association only because of the disequilibrium. Here, we describe an initial study of the nature of linkage disequilibrium and genetic variation, in population samples from different regions of the world, in a larger segment of the ADH cluster (including the three Class I ADH genes and ADH7). Linkage disequilibrium across 40 kb of the Class I ADH cluster is moderate to strong in all population samples that we studied. We observed nominally significant pairwise linkage disequilibrium, in some populations, between the ADH7 site and some Class I ADH sites, at moderate values and at a molecular distance as great as 100 kb. Our data indicate (1) that most ADH-alcoholism association studies have failed to consider many sites in the ADH cluster that may harbor etiologically significant alleles and (2) that the relevance of the various ADH sites will be population dependent. Some individual sites in the Class I ADH cluster show Fst values that are among the highest seen among several dozen unlinked sites that were studied in the same subset of populations. The high Fst values can be attributed to the discrepant frequencies of specific alleles in eastern Asia relative to those in other regions of the world. These alleles are part of a single haplotype that exists at high (>65%) frequency only in the eastern-Asian samples. It seems unlikely that this haplotype, which is rare or unobserved in other populations, reached such high frequency because of random genetic drift alone. en_US
dc.description.sponsorship This work was funded, in part, by National Institute of Alcohol Abuse and Alcoholism grant AA09379. Support was also provided by a grant (to K.K.K. and J.R.K.) from the Alfred P. Sloan Foundation for collection of population samples, by a contract (to K.K.K.) from the National Institute of Diabetes and Digestive and Kidney Diseases, and by grants (to R.B.L.) from the National Health Research Institute (Taiwan, ROC; NHRI-EX91-8939SP) and the National Science Council (Taiwan, ROC; NSC 90-2314-B-016-081). en_US
dc.format.extent 40288 bytes en_US
dc.format.mimetype application/pdf en_US
dc.language.iso en_US en_US
dc.publisher University of Chicago Press: American Journal of Human Genetics en_US
dc.title A global perspective on genetic variation at the ADH genes reveals unusual patterns of linkage disequilibrium and diversity en_US
dc.type Article en_US
dc.identifier.url http://dx.doi.org/10.1086/341290

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