Human COL6A1: Genomic characterization of the globular domains, structural and evolutionary comparison with COL6A2
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The αl(VI) and a2(VI) chains of type VI collagen (nonfibrillar) are highly similar and are encoded by single-copy genes in close proximity on human Chromosome (Chr) 21q22.3, a gene-rich region that has proved refractory to cloning. For the αl(VI) chain, only the regions encoding the triple-helical and the promoter have been characterized hitherto. To facilitate our study of the role of this gene in the phenotype of Down syndrome, we have cloned and sequenced the amino- and carboxyl-terminal globular domains of COL6A1. The amino-terminal domain 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 intron-exon structures of their globular domains differ markedly. Conservation is limited to the exons encoding amino acids immediately adjacent to the triple-helical region, including the cysteine residues essential for the structure of mature collagen VI. The intron-exon structures 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 duplication before the divergence of the reptilian and mammalian lineages.
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- Chu M-L, Pan T-C, Conway D, Kuo HJ, Glanville RW, Timpl R, Mann K, Deutzmann R (1989) Sequence analysis of αl(VI) and α2(VI) chains of human type VI collagen reveals internal triplication of globular domains similar to the domains of von Willebrand factor and two α2(VI) chain variants that differ in the carboxy terminus. EMBO J 8, 1939–1946PubMedGoogle Scholar
- Sambrook J, Fritsch EF, Maniatis T (1989) Molecular Cloning: A Laboratory Manual, 2nd ed. (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press)Google Scholar
- Timpl R, Engel J (1987) Type VI collagen. In Structure and Function of Collagen Types, R Mayne, RE Burgeson, eds. (Orlando, FL: Academic Press), pp 105–143Google Scholar