Considerable haplotype diversity within the 23kb encompassing the ADH7 gene.
BACKGROUND
Of the seven known human alcohol dehydrogenase (ADH) genes, the non-liver 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.
Han
Yi
Y
Department of Genetics, Yale University, School of Medicine, New Haven, CT 06520-8005, USA.
Oota
Hiroki
H
Osier
Michael V
MV
Pakstis
Andrew J
AJ
Speed
William C
WC
Odunsi
Adekunle
A
Okonofua
Friday
F
Kajuna
Sylvester L B
SL
Karoma
Nganyirwa J
NJ
Kungulilo
Selemani
S
Grigorenko
Elena
E
Zhukova
Olga V
OV
Bonne-Tamir
Batsheva
B
Lu
Ru-B
RB
Parnas
Josef
J
Schulz
Leslie O
LO
Kidd
Judith R
JR
Kidd
Kenneth K
KK
D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D000483:Alleles; D004247:DNA / Q000235:genetics; D005006:Ethnicity; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide
D004247:DNA; D000426:Alcohol Dehydrogenase