Alcw1^DBA/2J
QTL Variant Detail

Summary

• QTL variant: Alcw1^DBA/2J
• Name: alcohol withdrawal 1; DBA/2J
• MGI ID: MGI:2153882
• QTL: Alcw1 Location: Chr1:170868354-171966357 bp Genetic Position: Chr1, cM position of peak correlated region/allele: 80.33 cM
• QTL Note: genome coordinates based on the marker associated with the peak LOD score

Variant origin

• Strain of Specimen: DBA/2J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased alcohol withdrawal severity compared to C57BL/6J. (J:40532)
• Inheritance: Not Specified

Notes

Candidate Genes

J:98595

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.

On mouse Chromosome 1, several candidate genes were identified for Ap1q at 60 cM andAlcw1 at 95.8 cM. Candidate genes for Ap1q are Akp3 (51.7 cM), Gbx2 (65 cM), and Pam (57.5 cM). Candidate genes for Alcw1 are Adss, 2810484M10Rik, and Mark1.

J:98587

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.

On mouse Chromosome 1, several candidate genes were identified for Alcw1 at 95.8 cM, Alcdp1 (95.8 cM), and Actre1 (85 cM). The highest priority candidate genes identified for chromosome 1 ethanol-related QTLs are Myoc (83.6 cM), Pou2f1 (87.2 cM), Mgst3, Aldh9a1, Sdhc, Kcnj9 (94.2 cM), Darc (94 cM), and Srp9. Other candidate genes with a ranking of modest priority were identified but are not listed here.

Mapping and Phenotype information for this QTL, its variants and associated markers

J:40532

Authors 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, Alcw1 (LOD = 5.6). This locus is in proximity to D1Mit206 on mouse Chromosome 1 and accounts for about 6% of the total phenotypic variance in alcohol withdrawal between D2 and B6 strains (26% of the genetic variance).

J:36168

Linkage 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.

References

• Original: J:40532 Buck KJ, et al., Quantitative trait loci involved in genetic predisposition to acute alcohol withdrawal in mice. J Neurosci. 1997 May 15;17(10):3946-55
• All: 6 reference(s)