Mapping novel genetic loci associated with female liver weight variations using Collaborative Cross mice

Area of Science:

• Genetics
• Animal Models
• Complex Trait Analysis

Background:

• Liver weight is a polygenic trait with population-specific variations.
• Understanding its genetic architecture is crucial for identifying genes related to hepatomegaly and associated diseases.

Purpose of the Study:

• To map quantitative trait loci (QTL) associated with baseline liver weight in mice using the Collaborative Cross (CC) resource.
• To investigate the genetic factors contributing to liver weight variation and potential sex differences.

Main Methods:

• Liver weight was measured in 506 mice from 39 Collaborative Cross (CC) lines.
• Genomic DNA was genotyped using high-density single nucleotide polymorphic markers.
• Quantitative trait locus (QTL) mapping was performed to identify genetic loci influencing liver weight.

Main Results:

• Significant variation in liver weight was observed between CC lines (P < 0.05).
• Broad-sense heritability (H^2) was 0.32, and genetic coefficient of variation (CVG) was 0.28.
• A significant QTL (LWL1) was identified on chromosome 8 in females; three suggestive QTL (LWL2-4) were mapped on chromosomes 4, 12, and 13.

Conclusions:

• This study is the first to use the CC resource for mapping QTL associated with baseline mouse liver weight.
• Liver weight is a complex trait influenced by multiple genetic factors.
• Significant sex differences in genetic control of liver weight were observed.