Integrative genetics analysis of cartilage gene expression.

摘要

Most knowledge regarding the role of genes involved in the cartilage development has been derived from studies that provide insights only into the functions of individual genes or developmental pathways. I used systems genetics methods to study the development of cartilage in mice by integration of global cartilage gene expression profiles, bone phenotypic data and genetic perturbation. A co-expression network analysis was used to identify modules of co-expressed genes, which were then examined for relationships with bone geometry and density. One module (designated "salmon") exhibited significant correlation with femur length (r=0.42), anterio-posterior diameter (r=0.42), medial-lateral diameter (r=0.58) and bone mineral density (r=0.48). Genes from this module were also used to identify the potential regulators of chondrocyte development. Highly connected genes (n=28) in the modules were tested using in vitro experiments. Five genes were found to have function in chondrocyte differentiation. Two of these, Hspd1 and Cdkn1a, have previously known functions in chondrocyte development while the other three, Bhlhb9, Cugbp1 and Spcs3 (all salmon module genes), were novel genes. This integrative analysis provided a systems-level view of cartilage development and identified genes that may be involved in bone diseases.