title: Human COL6A1: genomic characterization of the globular domains, structural and evolutionary comparison with COL6A2.
abstract: The alpha1(VI) and alpha2(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 alpha1(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.
authors.affiliation: Academic Unit of Medical and Community Genetics (Imperial College School of Medicine), Kennedy Galton Centre, Level 8V, Northwick Park and St Mark's NHS Trust, Harrow HA1 3UJ, England, UK.
authors.forename: D
authors.initials: D
authors.lastname: Trikka
authors.forename: T
authors.initials: T
authors.lastname: Davis
authors.forename: V
authors.initials: V
authors.lastname: Lapenta
authors.forename: C
authors.initials: C
authors.lastname: Brahe
authors.forename: A M
authors.initials: AM
authors.lastname: Kessling
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002645:Chickens; D002874:Chromosome Mapping; D003094:Collagen / Q000737:chemistry* / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D015394:Molecular Structure; D005810:Multigene Family; D013045:Species Specificity
chemical_list: D018076:DNA, Complementary; D003094:Collagen