Using mouse genetics to understand human skeletal disease

Abstract

Technological advances have enabled the study of the human genome in incredible detail with relative ease. However, our ability to interpret the functional significance of the millions of genetic variants present within each individual is limited. As a result, the confident assignment of disease-causing variant calls remains a significant challenge. Here we explore how mouse genetics can help address this deficit in functional genomic understanding. Underpinned by marked genetic correspondence, skeletal biology shows inter-species similarities which provide important opportunities to use data from mouse models to direct research into the genetic basis of skeletal pathophysiology. In this article we outline critical resources that may be used to establish genotype/phenotype relationships in skeletal tissue, identify genes with established skeletal effects and define the transcriptome of critical skeletal cell types. Finally, we outline how these mouse resources might be utilized to progress from a list of human sequence variants toward plausible gene candidates that contribute to skeletal disease.

Keywords: Genetic analysis; Genomics; Mouse genetics; Skeletal disease; Skeletal phenotyping; Skeleton.