Experiment
Linkage analysis was performed on male animals from a series of Recombinant QTL Introgression (RQI) strains (derived from BALB/cJ or CXBI donor DNA on a C57BL/6ByJ genetic background) to identify QTLs associated with alcohol consumption. Adult male animals from 43 B.C RQI strains and 35 B.I strains were analyzed using a 2-bottle choice test. Progenitor strains BALB/cJ and CXBI exhibit lower ethyl alcohol consumption (EAC) compared to progenitor strain C57BL/6ByJ. Three hundred ninety-six microsatellite markers were used for linkage analysis.
Composite interval mapping identified several significant linkages to ethyl alcohol consumption on mouse Chromosome 6 at 36.5 cM (Eac1, LOD=3.6, P<0.001), 42.5 cM (Eac2, LOD=3.11, P<0.001), 62.2 cM (Eac3, LOD=2.09,P<0.01), and 73.5 cM (Eac4, LOD=3.28, P<0.001). C57BL/6ByJ-derived alleles at Eac1, Eac2, Eac3, and Eac4 confer increased ethyl alcohol consumption.
The RQI donor block region for Eac1 and Eac2 spans 33.5 cM - 48.2 cM. Eila2 (36.5 cM), Etlm3 (30 cM), Rear1 (36.5 cM), Bits2 (37 cM), and Taste5 (48 cM) are previously identified behavior and preference QTLs mapping to this interval. Potential candidate genes for Eac1 and Eac2 include V1rb2 (37 cM), Lrrtm1, Lrrtm4, Grm7, Gpr175, Gpr27, Lrrn1, Prokr1 (formerly Gpr73), Grip2, and Chchd4.
The RQI donor block for Eac3 spans 46 cM - 65.5 cM. Potential candidate genes found within this interval include Camk1 (48.7 cM), Gnb3 (60.19 cM), Tas2r104 (62 cM), Tas2r105 (62 cM), Tas2r106 (62 cM), Tas2r107 (62 cM), Tas2r130 (62 cM), Tas2r102 (63.4 cM), Tas2r115 (63.4 cM), Tas2r120 (63.4 cM), and Grin2b (64.5 cM). Previously identified behavior and preference QTLs located near Eac3 include Taste5(48.1 cM), Taste8 (49.5 cM), Qui (50.5 cM), Aaj3 (52.5 cM), Btts (63.3 cM),Mop1 (63.3 cM), Soa (63.4 cM), and Etohcta6 (63.6 cM).
Kcnj8 at 70 cM is a potential candidate gene for Eac4.
On mouse Chromosome 12, significant linkage to ethyl alcohol consumption mapped to 51 cM (Eac5, LOD=2.94, P<0.01) using composite interval mapping. The RQI donor block for Eac5 spans 46 cM - 58 cM. Marq4 is a previously identified QTL mapping to this interval and Calm1 is a potential candidate gene for Eac5. A suggestive locus named Eac6 (LOD=2.36, P<0.2), later confirmed by multiple interval mapping, is located at 21 cM. The RQI donor block spans 16 cM - 29 cM. Potential candidate genes for Eac6 include Prkch-rs1 (29 cM), and Stxbp6. Previously identified QTLs mapping to this locus include Rear2 (16 cM), Cocia1 (23 cM), Drb5 (25 cM), Aaq2 (27 cM), and Vacq7 (1 cM). C57BL/6ByJ-derived alleles at Eac5 and Eac6 confer increased ethyl alcohol consumption.
Analysis Tools