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Considerable Haplotype Diversity within the 23kb Encompassing the ADH7 Gene
Author(s) -
Han Yi,
Oota Hiroki,
Osier Michael V.,
Pakstis Andrew J.,
Speed William C.,
Odunsi Adekunle,
Okonofua Friday,
Kajuna Sylvester L.B.,
Karoma Nganyirwa J.,
Kungulilo Selemani,
Grigorenko Elena,
Zhukova Olga V.,
BonneTamir Batsheva,
Lu RuB,
Parnas Josef,
Schulz Leslie O.,
Kidd Judith R.,
Kidd Kenneth K.
Publication year - 2005
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000191769.92667.04
Subject(s) - linkage disequilibrium , haplotype , genetics , single nucleotide polymorphism , biology , tag snp , snp , adh1b , epistasis , genetic association , gene , population , evolutionary biology , allele , genotype , branched chain alpha keto acid dehydrogenase complex , biochemistry , demography , sociology , dehydrogenase , enzyme
A bstract : Background: Of the seven known human alcohol dehydrogenase ( ADH ) genes, the nonliver expressed ADH7 gene codes for the enzyme with the highest maximal activity for ethanol. Previous study from our laboratory has suggested that ADH7 has an epistatic role for protection against alcoholism based on a single ADH7 SNP. Methods: We have now studied seven SNPs, additional populations for the SNP previously examined, and six more new SNPs, across 23 kb of ADH7 in 38 population samples originating from different geographical regions of the world. Results: The overall linkage disequilibrium is moderate to strong across this region even though considerable 7‐SNP haplotype diversity is observed. This uncommonly high haplotype diversity is explained by high LD within each “half,” the three upstream SNPs and the four downstream SNPs, but near randomization between the “halves.” This division significantly simplified the haplotype pattern: only four major haplotypes account for almost all chromosomes in all populations in each “half.” Conclusions: The low linkage disequilibrium between these two “halves” suggests multiple recombination(s) have occurred in this region, specifically, within intron 7. The absence of strong LD between the functional variation in ADH1B that is strongly associated with alcoholism and any of the variation in ADH7 supports the genetic independence of ADH7 in association studies. Thus, the previously observed epistatic effect of ADH7 cannot be explained by its linkage disequilibrium with a causative factor in ADH1B .