Partial structure of the human alpha 2(IV) collagen chain and chromosomal localization of the gene (COL4A2).

We have isolated a 2.1-kb cDNA clone from a human placental library encoding part of the alpha 2 chain of collagen IV, a major structural protein of basement membranes. The DNA sequence encodes 446 amino acids in the triple-helical domain plus the 227 amino acids of the carboxy-terminal globular domain. The latter structure is composed of two homologous subdomains and is highly conserved between the alpha 1 and alpha 2 chains. The triple-helical domain contained seven interruptions of the Gly-X-Y repeat and these interruptions were in general larger than their counterparts in the alpha 1 chain. DNA from human rodent hybrid cell lines was analyzed under conditions in which there was no cross-hybridization of the alpha 2(IV) cDNA probe with the gene for the alpha 1(IV) collagen chain. An EcoRI fragment characteristic of the alpha 2 chain had a concordance of 0.97 with chromosome 13. This result was confirmed and extended with in situ localization of the gene at 13q34. Since the alpha 1(IV) gene has previously been localized to 13q34, the two type IV collagen genes reside in the same chromosome region (13q34), possibly in a gene cluster. The presence of the genes for type IV collagen chains on chromosome 13 excludes a primary role for these genes in adult polycystic kidney disease and X-linked forms of hereditary nephritis.