Chromosomal assignments of the genes coding for human types II, III, and IV collagen: a dispersed gene family.

Abstract

The human type II collagen gene, COL2A1, has been assigned to chromosome 12, the type III gene, COL3AI, to chromosome 2, and one of the type IV genes, COMA), to chromosome 13. These assignments were made by using cloned genes as probes on Southern blots of DNA from a panel of mouse/human somatic cell hybrids. The two genes of type I collagen, COLIAI and COL2AI, have been mapped previously to chromosomes 17 and 7, respectively. This family of conserved genes seems therefore to be dispersed throughout the genome.In vertebrates, the family of collagen proteins consists of a minimum of nine types of collagen molecules whose constituent chains are coded for by a minimum of 17 genes (1-5). Types I, II, and III, the so-called interstitial collagens, are the best characterized in terms of the amino acid and DNA sequences of their chains, and these data suggest that these chains are highly conserved evolutionarily. The genes coding for the interstitial chains have been isolated from several species and exhibit a very unusual and characteristic structure of a large number of relatively small exons [54 and 108 base pairs (bp)] at conserved positions along the length of the triple-helical Gly-X-Y portion (see ref. 6 for review). Type I collagen is a heteropolymer of two al(I) chains and one a2(I) chain, whereas types II and III are homopolymers of three al(II) and al(III) chains, respectively. These three interstitial collagen molecules each form highly ordered fibrils and are responsible for the tensile strength of tissue such as skin, bone, tendon (types I and III), and hyaline cartilage (type II) in which they are found.

Construction of a genetic map of human chromosome 17 by use of chromosome-mediated gene transfer.

“…The purified insert was radiolabeled with [32P]dCTP (Amersham) by the random-priming method (29). Hybridizations were done as described (30).…”

High recombination between two physically close human basement membrane collagen genes at the distal end of chromosome 13q.

“…The genes coding for these human collagen chains have been mapped to the distal region of chromosome 13q. The proal(IV) collagen gene (COMA)) was mapped to chromosome 13 (4,5) and localized to band q33-q34 by in situ hybridization (2,6), and the proa2(IV) collagen gene (COL4A2) was recently also mapped to band q33-q34 by in situ hybridization (7)(8)(9). Close localization of these genes has prompted the suggestion that they may be physically linked and perhaps be as close as the genes comprising the multigene clusters of a-and 8-globin (10).…”

Identification and characterization of the human type II collagen gene (COL2A1).

“…For example, the minor cartilage collagen chain 3a is highly homologous to al(II) collagen (25,41,42) and may or may not be genetically distinct. However, no evidence of other sequences homologous to CosHcoll has been found in Southern hybridizations, under conditions in which crosshybridization with the al(I) gene was visible (43), and copy number estimates are consistent with only one copy of the gene per haploid genome (R. Dalgleish, personal communication). It has been claimed that the 3a collagen chain differs from al(II) collagen in that it has a much larger peptide in place of the al(II) cyanogen bromide peptide CB9,7 (42).…”

“…The al(II) gene has been assigned to chromosome 12 (43,45). The gene is therefore not linked to the al(I) or a2(I) collagen genes, which map to chromosomes 17 and 7, respectively (4649), or to the al(III) or al(IV) collagen genes, which map to chromosomes 2 and 13, respectively (43).…”