TY - JOUR
T1 - Considerable haplotype diversity within the 23kb encompassing the ADH7 gene
AU - Han, Yi
AU - Oota, Hiroki
AU - Osier, Michael V.
AU - Pakstis, Andrew J.
AU - Speed, William C.
AU - Odunsi, Adekunle
AU - Okonofua, Friday
AU - Kajuna, Sylvester L.B.
AU - Karoma, Nganyirwa J.
AU - Kungulilo, Selemani
AU - Grigorenko, Elena
AU - Zhukova, Olga V.
AU - Bonne-Tamir, Batsheva
AU - Lu, Ru B.
AU - Parnas, Josef
AU - Schulz, Leslie O.
AU - Kidd, Judith R.
AU - Kidd, Kenneth K.
PY - 2005/12
Y1 - 2005/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=29944433047&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=29944433047&partnerID=8YFLogxK
U2 - 10.1097/01.alc.0000191769.92667.04
DO - 10.1097/01.alc.0000191769.92667.04
M3 - Article
C2 - 16385178
AN - SCOPUS:29944433047
SN - 0145-6008
VL - 29
SP - 2091
EP - 2100
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
IS - 12
ER -