Molecular genetics of chondrodysplasias, including clues to development, structure, and function

The extracellular matrix of cartilage consists of many macromolecules. Study of naturally occurring mutations in the genes that encode the chains of type II collagen (COL2A1) and type X collagen (COL10A1) in humans, engineered mutations in those genes in transgenic animals, and naturally occurring mutations in the chick aggrecan gene has identified important structural and functional aspects of these gene products. Direct biochemical studies, linkage analysis, and creation of transgenic animals containing mutations in matrix genes have provided considerable insight into the effects of mutations on normal structure and their role in joint disease.