HUMAN COL6A1 - GENOMIC CHARACTERIZATION OF THE GLOBULAR DOMAINS, STRUCTURAL AND EVOLUTIONARY COMPARISON WITH COL6A2

The alpha 1(VI) and alpha 2(VI) chains of type VI collagen (nonfibrill ar) are highly similar and are encoded by single-copy genes in close p roximity on human Chromosome (Chr) 21q22.3, a gene-rich region that ha s proved refractory to cloning. For the alpha 1(VI) chain, only the re gions encoding the triple-helical and the promoter have been character ized hitherto. To facilitate our study of the role of this gene in the phenotype of Down syndrome, we have cloned and sequenced the amino- a nd carboxyl-terminal globular domains of COL6A1. The aminoterminal dom ain consists of seven exons and, the carboxyl-terminal globular domain of nine exons. Together with the exons of the triple-helical domain, COL6A1 is encoded by a total of 36 exons spanning approximately 30 kb. Comparison of the genomic organization of COL6A1 and COL6A2 revealed that despite the similarity within their triple-helical domains, the i ntron-exon structures of their globular domains differ markedly. Conse rvation is limited to the exons encoding amino acids immediately adjac ent to the triple-helical region, including the cysteine residues esse ntial for the structure of mature collagen VI. The intron-exon structu res of these two genes are highly similar to the collagen VI genes of chicken. These data suggest that COL6A1 and COL6A2 arose from a gene d uplication before the divergence of the reptilian and mammalian lineag es.