A number of DNA sequences specific for collagen messenger RNAs and genes have been isolated, cloned in bacterial plasmids or bacteriophages, and studied in detail. Such sequences have been used to study regulatory mechanisms underlying the production of type I collagen in fibroblasts in culture, fibroblasts after viral transformation, and in tissues and organs during embryonic and fetal development. It is clear that a variety of mechanisms, transcriptional, translational and post-translational, are used by cells to regulate collagen production. The study of isolated collagen gene fragments coding for the alpha 2 collagen chain in sheep and chick have shown that many genes are very large, and are interrupted by as many as 50 intervening sequences. Additionally, the structure of the genes in the regions coding for the helical regions of the protein provides evidence that collagen genes may have arisen from the reduplication of a DNA segment containing a primordial collagen gene sequence. The availability of specific cloned collagen gene sequences will allow the precise chromosomal location of the collagen genes as well as the number and the linkage relationships between these genes. In addition, genetic disorders of connective tissue where alterations in collagen structure are implicated will now be amenable to analysis at the DNA level.
