Etohc3^DBA/2J
QTL Variant Detail

Summary

• QTL variant: Etohc3^DBA/2J
• Name: ethanol consumption 3; DBA/2J
• MGI ID: MGI:2157400
• QTL: Etohc3 Location: Chr9:52034478-52034599 bp Genetic Position: Chr9, cM position of peak correlated region/allele: 28.62 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
• Inheritance: Other (see notes)

Notes

Etohc3 exhibits additive inheritance.

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

J:52468

B6D2F2 (C57BL/6J x DBA/2J) and BXD Recombinant Inbred (RI) stains were analyzed to discover QTLs that affect ethanol consumption in mice. Regions on mouse Chromosome 2 and mouse Chromosome 9 showed significant associations with a preference for ethanol. Mouse Chromosome 2 marker D9Mit4 showed a significant association with the phenotype with a combined LOD score of 6.7. The Chromosome 9 QTL is designated as Etohc3.

J:109029

Candidate genes for alcohol consumption loci were screened using microarray analysis. A panel of 107 microarrays were screened using mRNA from 3 inbred strains and 6 coisogenic strains with known differences in alcohol consumption. A large set of identified genes were further refined by analyzing mRNA from a congenic line carrying DBA/2J-derived DNA from 9 cM - 58 cM on a C57BL/6J genetic background.

Candidate genes Pknox2, Scn4b, 9030425E11Rik, and 111003A03Rik coincide with Etohc3, an alcohol consumption QTL at 29 cM (chr9).

Other candidate genes in the chromosome 9 congenic interval identified by microarray analysis included Arhgef12, Acad11 (formerly 5730439E10Rik) Carm1, Cryab, Cox5a, Dlat, Fxyd6, Limd1, Nicn1, Nmnat3, Rbp1, Sc5d, Tcf12, Vps11, and Zfp291.

J:20482

Linkage analysis was performed using female animals from 19 BXD/Ty (B=C57BL/6J; D=DBA/2J) recombinant inbred (RI) strains to identify loci associated with ethanol drinking phenotypes. Parental strain C57BL/6J exhibits increased consumption of unsweetened10% ethanol, saccharin sweetened 3% and 10% ethanol, and 0.2% saccharin solution compared to parental strain DBA/2J. C57BL/6J also exhibits increased preference for 10% ethanol and 0.2% saccharin over water compared to DBA/2J. QTL analysis identified several loci linked to sweetened and unsweetened ethanol consumption and saccharin consumption on several mouse Chromosomes.

Linkage to 3% ethanol consumption mapped to 14 cM on mouse Chromosome 1 near D1Mit1. Significant linkage to 3% ethanol consumption and saccharin consumption mapped to 34 cM near D1Mit5.1, Myl1, and D1Byu1. Significant linkage to sweetened 3% and 10% ethanol consumption mapped to 70 cM on mouse Chromosome 1 near Ren2. Linkage to sweetened 3% and 10% ethanol consumption mapped to 88 cM near D1Mit16.

Linkage to sweetened and unsweetened 10% ethanol consumption mapped to 49 cM on mouse Chromosome 2 near D2Mc2. This locus was verified in a subsequent study (Phillips et al. 1998; J:52468) is named Etohc2 (ethanol consumption 2).

Linkage to sweetened 3% and 10% ethanol consumption and saccharin consumption mapped to 24 cM on mouse Chromosome 3 near D3Mit5. Linkage to unsweetened 10% ethanol consumption and sweetened 3% and 10% ethanol consumption mapped to 72 cM - 75 cM near Pmv26, Iapls2-14, and Lamr1-rs4.

Linkage to unsweetened 3% and 10% ethanol consumption and sweetened 10% ethanol consumption mapped to 57 cM - 61 cM on mouse Chromosome 4 near Lck and Slc9h1 (formerly Nhe1). Aldh4a1 at 66 cM is a potential candidate gene. Linkage to saccharin consumption and sweetened 3% and 10% ethanol consumption mapped to 81 cM - 82 cM near Tas1r3 (formerly Sac), D4Bir1, and Tel4q.

Linkage to unsweetened 3% and 10% ethanol consumption mapped to 11 cM on mouse Chromosome 7 near Nudt19 (formerly D7Rp2). Linkage to unsweetened 3% and 10% ethanol consumption and sweetened 10% ethanol consumption mapped to 57 cM near Rasl4.

Linkage to unsweetened 3% ethanol consumption mapped to 23 cM near D8Bir2, and significant linkage to saccharin consumption mapped to 60 cM near Xmmv29. This locus maps near previously identified saccharin QTL Cons3 at 67 cM.

Linkage to unsweetened 10% ethanol consumption mapped to 27 cM - 28 cM on mouse Chromosome 9 near Drd2, Ncam1, and Xmmv2. This locus was verified in a subsequent study and is named Etohc3 (ethanol consumption 3). Animals with C57BL/6J-derived alleles at Etohc3 exhibit 2.5-fold increased ethanol consumption compared to animals with DBA/2J-derived alleles.

Linkage to saccharin consumption mapped to 40 cM - 48cM on mouse Chromosome 13 near D13Mit9, Rasa1, and Arsb (formerly As-1), and to 52 cM - 58 cM nearLth1 and D13Bir1.

Linkage to sweetened 10% ethanol consumption mapped to 37 on mouse Chromosome 15 near D15Mit3.

Linkage to unsweetened 3% ethanol consumption is associated with marker D0Tu8 (formerly D17Tu8). This marker may possibly reside on Chromosome 17 but a definitive location is unknown.

Linkage to saccharin consumption and sweetened 3% and 10% ethanol consumption mapped to 18 cM - 21 cM on mouseChromosome 18 near Iapls3-7, D18Mit14, and Nr3c1 (formerly Grl1).

References

• Original: J:52468 Phillips TJ, et al., Genes on mouse chromosomes 2 and 9 determine variation in ethanol consumption. Mamm Genome. 1998 Dec;9(12):936-41
• All: 2 reference(s)