Short-term selective breeding as a tool for QTL mapping: ethanol preference drinking in mice

Area of Science:

• Genetics
• Behavioral Neuroscience
• Animal Science

Background:

• Quantitative trait locus (QTL) mapping is crucial for understanding complex traits.
• Selective breeding offers an underutilized approach for QTL analysis and validation.
• Recombinant inbred (RI) lines are commonly used for QTL studies.

Purpose of the Study:

• To explore short-term selective breeding as a tool for QTL mapping.
• To validate QTL findings from BXD RI lines using a novel selection method.
• To identify genomic regions associated with alcohol preference in mice.

Main Methods:

• Utilized an F2 intercross between C57BL/6J (B6) and DBA/2J (D2) mice.
• Established bidirectionally selected lines for high and low 10% ethanol preference over four generations.
• Employed microsatellite markers to analyze allele frequency divergence between selected lines.

Main Results:

• Significant divergence in alcohol preference observed between high and low lines by the first generation (realized heritability = 0.32).
• Preference ratios doubled in the high line compared to the low line by generation 4.
• Identified a probable QTL on chromosome 3 (near adhl locus; LOD ~2.9) and additional QTLs (LOD 2.4-2.6) by integrating selection line and RI data.

Conclusions:

• Short-term selective breeding is an effective strategy for QTL mapping of alcohol preference.
• This method successfully confirmed and refined QTL locations previously identified in BXD RI lines.
• Genomic regions on chromosome 3 are strongly implicated in the regulation of alcohol preference.