A comparison of selected quantitative trait loci associated with alcohol use phenotypes in humans and mouse models.
Evidence for genetic linkage to alcohol and other substance dependence phenotypes in areas of the human and mouse genome have now been reported with some consistency across studies. However, the question remains as to whether the genes that underlie the alcohol-related behaviors seen in mice are the same as those that underlie the behaviors observed in human alcoholics. The aims of the current set of analyses were to identify a small set of alcohol-related phenotypes in human and in mouse by which to compare quantitative trait locus (QTL) data between the species using syntenic mapping. These analyses identified that QTLs for alcohol consumption and acute and chronic alcohol withdrawal on distal mouse chromosome 1 are syntenic to a region on human chromosome 1q where a number of studies have identified QTLs for alcohol-related phenotypes. Additionally, a QTL on human chromosome 15 for alcohol dependence severity/withdrawal identified in two human studies was found to be largely syntenic with a region on mouse chromosome 9, where two groups have found QTLs for alcohol preference. In both of these cases, while the QTLs were found to be syntenic, the exact phenotypes between humans and mice did not necessarily overlap. These studies demonstrate how this technique might be useful in the search for genes underlying alcohol-related phenotypes in multiple species. However, these findings also suggest that trying to match exact phenotypes in humans and mice may not be necessary or even optimal for determining whether similar genes influence a range of alcohol-related behaviors between the two species.
Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, CA 92037, USA. cindye@scripps.edu
Cindy L
CL
Ehlers
Nicole A R
NA
Walter
Danielle M
DM
Dick
Kari J
KJ
Buck
John C
JC
Crabbe
D000437:Alcoholism / Q000235:genetics*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002755:Choice Behavior; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D004195:Disease Models, Animal; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics; D013045:Species Specificity
D002352:Carrier Proteins; C111442:MPDZ protein, human; D008565:Membrane Proteins; C491750:Mpdz protein, mouse