Disease relevance of COL9A1

• A mutation in COL9A1 causes multiple epiphyseal dysplasia: further evidence for locus heterogeneity [1].
• Evidence for a role of the genomic region of the gene encoding for the alpha1 chain of type IX collagen (COL9A1) in hip osteoarthritis: A population-based study [2].
• Transient-transfection analyses performed in rat chondrosarcoma (RCS) cells, human chondrosarcoma (HTB) cells, and NIH/3T3 cells showed that the COL9A1 promoter was active in RCS cells but not HTB or NIH/3T3 cells [3].
• These data may facilitate linkage studies with COL9A1 (or Col9a1) as a candidate gene for hereditary chondrodysplasias and osteoarthritis [4].

High impact information on COL9A1

• We considered the COL9A1 gene, located on chromosome 6q13, to be a candidate gene on the basis of the structural association with collagen types II and XI and because of the high expression in the human inner ear indicated by cDNA microarray [5].
• The analysis resulted in identification of three mutations in COMP and one in COL9A1, but none in the other two collagen IX genes [1].
• Screening of COL9A1 for mutations in the two probands from the families in which this gene was not involved in the recombinations failed to identify any disease-causing mutations [1].
• CONCLUSION: Our data suggest that susceptibility for hip OA is conferred within or close to the COL9A1 gene in linkage disequilibrium with the COL9A1 509-8B2 marker [2].
• Regulation of human COL9A1 gene expression. Activation of the proximal promoter region by SOX9 [3].

Biological context of COL9A1

• The COL9A1 gene is about 90 kb and consists of 38 exons [6].
• The COL9A1 gene contains two promoter regions, one driving expression of a long alpha1(IX) chain in cartilage (upstream) and one driving expression of a shorter chain in the cornea and vitreous (downstream) [3].
• A general drop of methylation in COL9A1 was apparent in tumors, when compared with blood and healthy breast tissue [7].
• Previously, COL19A1 was mapped to human chromosome 6q12-q14, where COL9A1 is also located [8].
• We identified and then genotyped twenty common single nucleotide polymorphisms (SNPs) from within COL9A1 in the 146 probands from our female THR-families and in 215 age-matched female controls [9].

Anatomical context of COL9A1

• The sequence encoded by exon 7, predicted from human COL9A1, is absent from both short and long forms of alpha1(IX) from bovine nucleus pulposus and articular cartilage [10].
• RT-PCR analysis using primers specific to COL9A1 isoforms 1 and 2 detected expression of both isoforms in human fetal cochlea [11].

Other interactions of COL9A1

• Here we report the complete structure for the human COL9A1 and the complete sequence for the human COL9A2 genes [6].
• Type IX collagen is composed of three polypeptides derived from the human genes COL9A1, COL9A2, and COL9A3 that assemble to form a mature collagen molecule with the structure alpha 1(IX)alpha 2(IX)alpha 3(IX) [12].
• Association of COL1A2, COL2A1 and COL9A1 and primary osteoarthritis in a founder population [13].
• The COL9A1 locus shows no recombination with the marker D6Z1 (Z = 27.61 at theta = O) and identifies the most likely locus order of KRAS1P-[D6Z1-COL9A1]-D6S30 [4].

Analytical, diagnostic and therapeutic context of COL9A1

• In this paper we confirm the mapping of the human COL9A1 gene to chromosome 6q12-q13 by fluorescence in situ hybridization utilizing two genomic clones which also contain short tandem repeat polymorphisms [4].
• Physical and linkage mapping of the human and murine genes for the alpha 1 chain of type IX collagen (COL9A1) [4].

References