Genetic analysis of complex traits in the emerging Collaborative Cross.

Area of Science:

• Mammalian genetics
• Systems genetics
• Genomic research

Background:

• The Collaborative Cross (CC) is a novel mouse recombinant inbred strain panel designed for mammalian systems genetics.
• Partially inbred CC lines were utilized to assess the genetic properties and utility of this developing resource.

Purpose of the Study:

• To evaluate the genetic properties and utility of the Collaborative Cross (CC) mouse model for systems genetics.
• To demonstrate the enhanced ability to map causative loci for complex diseases using the CC resource.

Main Methods:

• Genome-wide analysis of incipient CC strains.
• Quantitative trait locus (QTL) mapping using inferred haplotypes.
• Expression QTL (eQTL) mapping at 1-Mb resolution.

Main Results:

• CC strains exhibit high genetic diversity, balanced allele frequencies, and dense recombination sites.
• Inferred haplotype analysis improved QTL mapping power and reduced false discovery rates.
• A record number of expression QTLs were discovered, with local eQTLs mapped at 1-Mb resolution.

Conclusions:

• The Collaborative Cross is an ideal resource for mammalian systems genetics due to its genetic and phenotypic diversity.
• The CC resource significantly enhances the ability to identify and prioritize candidate genes for complex traits and diseases.
• This study validates the utility of the CC for high-resolution mapping of genetic loci underlying complex traits.