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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Structure of the human type IV collagen COL4A6 gene, which is mutated in Alport syndrome-associated leiomyomatosis.

Basement membrane (type IV) collagen, a subfamily of the collagen protein family, is encoded by six distinct genes in mammals. Three of those, COL4A3, COL4A4, and COL4A5, are linked with Alport syndrome (hereditary nephritis). Patients with leimoyomatosis associated with Alport syndrome have been shown to have deletions in the 5' end of the COL4A6 gene, in addition to having deletions in COL4A5 (Zhou et al., Science 261: 1167-1169, 1993). The human COL4A6 gene is reported to be 425 kb as determined by mapping of overlapping YAC clones by probes for its 5' and 3' ends. In the present study we describe the complete exon/intron size pattern of the human COL4A6 gene. The 12 lambda phage clones characterized in the study spanned a total of 110 kb, including 85 kb of the actual gene and 25 kb of flanking sequences. The overlapping clones contained all 46 exons of the gene and all introns, except for intron 2. Since the total size of the exons and all introns except for intron 2 is about 85 kb, intron 2 must be about 340 kb. All exons of the gene were assigned to EcoRI restriction fragments to facilitate analysis of the gene in patients with leiomyomatosis associated with Alport syndrome. The exon size pattern of COL4A6 is highly homologous with that of the human and mouse COL4A2 genes, with 27 of the 46 exons of COL4A6 being identical in size between the genes.[1]


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