Alcdp1^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Alcdp1^C57BL/6J
• Name: alcohol dependency 1; C57BL/6J
• MGI ID: MGI:3050681
• QTL: Alcdp1 Location: unknown 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: C57BL/6J

Variant description

• Allele Type: QTL
• Inheritance: Dominant

Notes

Candidate Genes

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:91457

Linkage analysis was performed on 400 (C57BL/6J x DBA/2J)F2 animals to identify QTLs associated with alcohol withdrawal severity using 104 polymorphic markers spaced on average 13.1 cM apart. Animals were exposed to ethanol vapors for 72 hours and then assessed for handling-induced convulsions at different time points.

Significant linkage mapped to distal mouse Chromosome 1 near D1Mit206 (95.8 cM, LOD=7.6). This locus is named Alcdp1 (alcohol dependency 1). The confidence interval of Alcdp1 spans 86 cM-112 cM. Homozygosity for DBA/2J-derived alleles at Alcdp1 confers increased alcohol withdrawal severity compared to animals heterozygous or homozygous for C57BL/6J-derived alleles. Potential candidate genes that map to this region are Kcnj10 (93.5 cM) and Itpkb (100 cM). This locus explains 26% of the genetic variance and 12% of the phenotypic variance, and is syntenic to human Chromosome 1q21-43. Mapping of congenic strains narrowed the Alcdp1 QTL interval to 89 cM - 106.3 cM.

A second QTL showing linkage to alcohol withdrawal severity mapped to mid-distal mouse Chromosome 19 between D19Mit13 (33 cM) and D19Mit10 (47 cM) with LOD=5.3. This locus is named Alcdp2 and explains 19% of the genotypic variance and 8% of the phenotypic variance. DBA/2J-derived alleles confer increased alcohol withdrawal severity with an additive mode of inheritance. The confidence interval for Alcdp2 is very broad, from 36.5 cM - terminus. Potential candidate genes for Alcdp2 are Cyp17a1 (46 cM), Rbp4 (38 cM), Sorbs1 (36.5 cM), and Cyp2c29 (27 cM). Alcdp2 is syntenic to human Chromosome 10q23-26.

A provisional sex-dependent QTL mapped to 37 cM on mouse Chromosome 13 near D13Mit224 (LOD=2.9). DBA/2J-derived alleles confer increased alcohol withdrawal severity in male mice at this locus. This locus explains 17% of the genetic variance and 8% of the phenotypic variance. Congenic strains will be used to confirm this locus.

References

• Original: J:91457 Buck KJ, et al., Mapping murine loci for physical dependence on ethanol. Psychopharmacology (Berl). 2002 Apr;160(4):398-407
• All: 1 reference(s)