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Publication : Systems genetics analysis of mouse chondrocyte differentiation.

First Author  Suwanwela J Year  2011
Journal  J Bone Miner Res Volume  26
Issue  4 Pages  747-60
PubMed ID  20954177 Mgi Jnum  J:184243
Mgi Id  MGI:5320540 Doi  10.1002/jbmr.271
Citation  Suwanwela J, et al. (2011) Systems genetics analysis of mouse chondrocyte differentiation. J Bone Miner Res 26(4):747-60
abstractText  One of the goals of systems genetics is the reconstruction of gene networks that underlie key processes in development and disease. To identify cartilage gene networks that play an important role in bone development, we used a systems genetics approach that integrated microarray gene expression profiles from cartilage and bone phenotypic data from two sets of recombinant inbred strains. Microarray profiles generated from isolated chondrocytes were used to generate weighted gene coexpression networks. This analysis resulted in the identification of subnetworks (modules) of coexpressed genes that then were examined for relationships with bone geometry and density. One module exhibited significant correlation with femur length (r = 0.416), anteroposterior diameter (r = 0.418), mediolateral diameter (r = 0.576), and bone mineral density (r = 0.475). Highly connected genes (n = 28) from this and other modules were tested in vitro using prechondrocyte ATDC5 cells and RNA interference. Five of the 28 genes were found to play a role in chondrocyte differentiation. Two of these, Hspd1 and Cdkn1a, were known previously to function in chondrocyte development, whereas the other three, Bhlhb9, Cugbp1, and Spcs3, are novel genes. Our integrative analysis provided a systems-level view of cartilage development and identified genes that may be involved in bone development.
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