Genetic association of a GABAA receptor γ2 subunit variant with severity of acute physiological dependence on alcohol

Genetic association of a GABAA receptor γ2 subunit variant with severity of acute physiological... The ultimate goal of quantitative trait locus (QTL) mapping is to identify the genes affecting complex traits. Using animal models, we recently identified QTLs on mouse Chromosomes (Chrs) 1, 4, and 11 affecting genetic predisposition to acute alcohol withdrawal. Among mice derived from the C57BL/6J (B6) and DBA/2J (D2) inbred strains, the locus identified on Chr 11 (∼20 cM) accounted for 12% of the genetic variability in withdrawal liability. Candidate genes in proximity to this QTL encode the γ2, α1, and α6 subunits of GABAA receptors. The present studies identify a polymorphism between the B6 and D2 strains in the γ2 subunit gene, Gabrg2, and expand genotypic analysis to their BXD recombinant inbred strains. This polymorphism predicts a difference in amino acid sequence (Ala-11 vs. Thr-11) within the extracellular amino-terminal region of the γ2 subunit. Analysis using BXD strain means for acute alcohol withdrawal severity suggests that the γ2 subunit polymorphism is genetically correlated with alcohol withdrawal severity. This is the first report that QTL mapping for an alcohol-related trait has successfully led to the identification of a polymorphic candidate gene product that is genetically associated with the trait. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Mammalian Genome Springer Journals

Genetic association of a GABAA receptor γ2 subunit variant with severity of acute physiological dependence on alcohol

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Publisher
Springer Journals
Copyright
Copyright © 1998 by Springer-Verlag New York Inc.
Subject
Life Sciences; Cell Biology; Animal Genetics and Genomics; Human Genetics
ISSN
0938-8990
eISSN
1432-1777
D.O.I.
10.1007/s003359900909
Publisher site
See Article on Publisher Site

Abstract

The ultimate goal of quantitative trait locus (QTL) mapping is to identify the genes affecting complex traits. Using animal models, we recently identified QTLs on mouse Chromosomes (Chrs) 1, 4, and 11 affecting genetic predisposition to acute alcohol withdrawal. Among mice derived from the C57BL/6J (B6) and DBA/2J (D2) inbred strains, the locus identified on Chr 11 (∼20 cM) accounted for 12% of the genetic variability in withdrawal liability. Candidate genes in proximity to this QTL encode the γ2, α1, and α6 subunits of GABAA receptors. The present studies identify a polymorphism between the B6 and D2 strains in the γ2 subunit gene, Gabrg2, and expand genotypic analysis to their BXD recombinant inbred strains. This polymorphism predicts a difference in amino acid sequence (Ala-11 vs. Thr-11) within the extracellular amino-terminal region of the γ2 subunit. Analysis using BXD strain means for acute alcohol withdrawal severity suggests that the γ2 subunit polymorphism is genetically correlated with alcohol withdrawal severity. This is the first report that QTL mapping for an alcohol-related trait has successfully led to the identification of a polymorphic candidate gene product that is genetically associated with the trait.

Journal

Mammalian GenomeSpringer Journals

Published: Dec 1, 1998

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