MouseFM

MouseFM provides methods for genetic finemapping in inbred mice by taking advantage of their very high homozygosity rate (>95%).

Key Features:

• Real-time variant querying: Public genome-wide genotype data covering more than 74 million variant sites is queried efficiently in real-time to provide variants compatible with observed phenotype differences between strains.
• Variant filtering: Variants can be filtered by molecular consequences and by corresponding molecular impact.
• Candidate gene generation: Candidate gene lists can be generated from variant lists on the fly.
• Finemapping with annotation: Fine-mapping together with annotation or filtering of results is provided within the package.

Scientific Applications:

• Expression quantitative trait loci analysis: Fine-mapping was assessed for about 10,000 genes in expression data sets from neutrophils and CD4+ T cells across 20 inbred mouse strains, identifying candidate variants and haplotypes for many previously reported eQTLs.
• Albinism candidate identification: MouseFM reports a missense variant in the Tyr gene as the only variant allele of moderate or high molecular impact shared by albino mice, matching the previously reported causal variant.
• Interfrontal bone formation analysis: Fine-mapping using four strains with and five strains without interfrontal bone results in 12 candidate genes, three of which are related to skull shaping abnormality.
• Dystrophic cardiac calcification mapping: Comparing nine strains showing the phenotype with eight strains lacking it identifies one moderate impact variant in the known causal gene Abcc6.

Methodology:

MouseFM uses genotypic data of 37 inbred mouse strains together with user-provided phenotypic data to propose candidate variants and genes for the phenotype under study.