Mouse inbred strain sequence information and yin-yang crosses for quantitative trait locus fine mapping

Area of Science:

• Genetics
• Genomics
• Bioinformatics

Background:

• Mouse inbred strains offer valuable resources for mapping quantitative trait loci (QTL) due to shared ancestry and available sequence/phenotype data.
• A key challenge in QTL mapping using sequence data is the ambiguous determination of the allelic state within a given strain.

Purpose of the Study:

• To propose and evaluate a general approach for improving quantitative trait loci (QTL) mapping resolution.
• To introduce and assess the efficacy of "yin-yang" crosses for fine mapping QTL in mouse models.

Main Methods:

• The study proposes a general approach involving crossing initial strains with new strains, termed "yin-yang" crosses.
• The publicly available single nucleotide polymorphism (SNP) database of mouse chromosome 16 was utilized to evaluate mapping resolution.
• The effectiveness of the yin-yang approach was assessed by analyzing the reduction in QTL-containing intervals.

Main Results:

• On average, using four inbred strains with the yin-yang approach resulted in a modest improvement in mapping resolution, reducing the QTL interval by at most half.
• Significant variability in mapping resolution was observed across different regions of chromosome 16.
• The study found that selecting a small subset of strains can substantially contribute to fine mapping QTL when a large number of strains are available.

Conclusions:

• The yin-yang crossing strategy offers a complementary approach to enhance the resolution of quantitative trait loci (QTL) mapping.
• While average resolution improvement may be moderate, the variability suggests potential for significant gains in specific genomic regions.
• This method holds promise for fine mapping QTL, particularly when leveraging a diverse panel of mouse inbred strains.