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Confirmation and Genetic Dissection of a Major Quantitative Trait Locus for Alcohol Preference Drinking
Author(s) -
Ruf Cathy,
CarosoneLink Phyllis,
Springett Justin,
Bennett Beth
Publication year - 2004
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000145693.58448.95
Subject(s) - quantitative trait locus , congenic , genetics , biology , backcrossing , locus (genetics) , trait , phenotype , candidate gene , gene , genetic linkage , chromosome , chromosome 4 , family based qtl mapping , gene mapping , computer science , programming language
Objective: In previous work, we created congenic strains that carry the DBA/2IBG (D2) region for alcohol preference on chromosome 2, on an otherwise C57BL/6IBG (B6) background. Here, we report construction and testing of interval‐specific congenic recombinant strains (ISCRSs) for the purpose of narrowing the quantitative trait loci (QTL) interval. Methods: ISCRSs were derived by identifying mice that carry recombination events in the D2 interval, during the backcrossing for congenics. Recombinant mice were backcrossed to B6, and progeny that carry the reduced chromosome 2 region were tested for its effect on the alcohol preference phenotype. Results: We developed multiple ISCR strains, which spanned the QTL interval. Three of these showed the D2 phenotype of reduced alcohol consumption. The overlap of two of these strains reduced the QTL interval from 66.8 to 3.5 Mb. A third positive ISCRS suggests the possibility of a second, linked QTL. Conclusions: Use of ISCRSs can narrow a QTL region to a few Mb. This reduced interval size will facilitate identification of candidate genes, through bioinformatics, gene expression, and DNA sequencing strategies. Potential difficulties, including reduced power as a result of variable phenotypes or small effect size, are discussed.