Genomewide SNP screen to detect quantitative trait loci for alcohol preference in the high alcohol preferring and low alcohol preferring mice.
BACKGROUND
The high and low alcohol preferring (HAP1 and LAP1) mouse lines were selectively bred for differences in alcohol intake. The HAP1 and LAP1 mice are essentially noninbred lines that originated from the outbred colony of HS/Ibg mice, a heterogeneous stock developed from intercrossing 8 inbred strains of mice.


METHODS
A total of 867 informative SNPs were genotyped in 989 HAP1 x LAP1 F2, 68 F1s, 14 parents (6 LAP1, 8 HAP1), as well as the 8 inbred strains of mice crossed to generate the HS/Ibg colony. Multipoint genome wide analyses were performed to simultaneously detect linked QTLs and also fine map these regions using the ancestral haplotypes.


RESULTS
QTL analysis detected significant evidence of association on 4 chromosomes: 1, 3, 5, and 9. The region on chromosome 9 was previously found linked in a subset of these F2 animals using a whole genome microsatellite screen.


CONCLUSIONS
We have detected strong evidence of association to multiple chromosomal regions in the mouse. Several of these regions include candidate genes previously associated with alcohol dependence in humans or other animal models.
Bice
Paula
P
Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana 46202, USA. pbice@iupui.edu
Valdar
William
W
Zhang
Lili
L
Liu
Lixiang
L
Lai
Dongbing
D
Grahame
Nicholas
N
Flint
Jonathan
J
Li
Ting-Kai
TK
Lumeng
Lawrence
L
Foroud
Tatiana
T
D000428:Alcohol Drinking / Q000235:genetics*; D019973:Alcohol-Related Disorders / Q000235:genetics*; D000818:Animals; D005260:Female; D023281:Genomics; D008297:Male; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci