Summary |
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Variant origin |
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Variant description |
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Phenotypes |
View phenotypes and curated references for all genotypes (concatenated display).
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Notes |
Candidate Genes
Mpdz, a candidate gene for the alcohol withdrawal QTL Alcw2 on mouse Chromosome 4, was examined in this study. Short term selected lines were generated from a (C57BL/6J x DBA/2J)F2 intercross. Animals were selected for high alcohol withdrawal (HAW) or low alcohol withdrawal (LAW) phenotypes and bred for 4 generations. DBA/2J-derived alleles at Mpdz were enriched in the HAW population whereas C57BL/6J-derived alleles were enriched in the LAW population. This association is significant and exceeds that predicted from genetic drift. Microarray analysis was used to identify genes showing alcohol-induced differential expression between inbred strains C57BL/6J and DBA/2J. These genes were then correlated to alcohol-related QTLs to identify potential candidate genes. The experiment involved identifying genes expressed differentially in alcohol-induced and non-induced animals but the following list of candidate genes are only for alcohol-induced states. Microarray analysis was used to identify genes showing alcohol-induced differential expression between inbred strains C57BL/6J and DBA/2J. These genes were then correlated to 6 previously identified alcohol-related QTLs to identify potential candidate genes. Two different Affymetrix microarrays were used in the analysis. Brain expression data from parental strains and 56 (DBA/2J x C57BL/6J)F2 intercross animals were used for analysis. Mapping and Phenotype information for this QTL, its variants and associated markersJ:40532Authors localized quantitative trait loci involved with alcohol dependence/genetic predisposition to acute alcohol withdrawal in mice. BXD (C57BL/6J x DBA/2J) strains, B6D2 F2 animals, and HAW (high alcohol withdrawal) LAW (low alcohol withdrawal) animals was used to identify a QTL, Alcw2 (LOD = 5.6). This locus is in proximity to Tyrp1 on mouse Chromosome 4 approximately 40 cM from the centromere and accounts for about 6% of the total phenotypic variance in alcohol withdrawal between D2 and B6 strains (26% of the genetic variance). J:36168Linkage analysis was performed on 21 BXD (B=C57BL/6J; D=DBA/2J) recombinant inbred (RI) strains at a marker resolution of 1 cM to detect loci associated with alcohol withdrawal severity. Parental strain DBA/2J exhibits greater alcohol withdrawal severity compared to C57BL/6J. Loci contributing to high risk of withdrawal, Alcw1 and Alcw2, were detected at distal mouse Chromosome 1 with a LOD score of 5.8, and at 38 cM on mouse Chromosome 4 with a LOD score of 5.7 near the b locus (Tyrp1), respectively. DBA/2J-derived alleles confer increased alcohol withdrawal severity at Alcw1 and Alcw2. A locus contributing to protection from severe alcohol withdrawal mapped to 20 cM on mouse Chromosome 11 with a LOD score of 4.1 near D11Mit174. DBA/2J-derived alleles confer decreased alcohol withdrawal severity at Alcw3. |
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References |
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 10/29/2024 MGI 6.24 |
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