Disease relevance of COL9A2

• Exon skipping mutation in the COL9A2 gene in a family with multiple epiphyseal dysplasia [1].
• Recently associations of COL9A2 (Trp2 allele) and COL9A3 (Trp3 allele) polymorphisms with lumbar disc disease characterized by sciatica have been reported [2].
• An allelic variation of the COL9A2 gene encoding the alpha(2)-chain of collagen IX has recently been identified as a genetic risk factor for intervertebral disc prolapse, resulting in a tryptophane (Trp) substitution at position 326 of the protein [3].
• The test statistics did not reach the significance threshold of 5% and so we could not show an association of COL9A2 with equine osteochondrosis [4].
• The most frequent mutation is R279W, which in a homozygous state results in rMED with bilateral clubfoot, MED, and "double layered" patella [5].

High impact information on COL9A2

• A mutation in the gene encoding the alpha 2 chain of the fibril-associated collagen IX, COL9A2, causes multiple epiphyseal dysplasia (EDM2) [6].
• An allele of COL9A2 associated with intervertebral disc disease [7].
• A tryptophan (Trp) allele (Trp2) was recently discovered in the COL9A2 gene that is associated with dominantly inherited LDD but is only present in about 4% of Finnish patients with LDD [8].
• Because of the exclusion of the EDM1 and EDM2 loci in some families, the existence of a third locus has been postulated [9].
• Type IX collagen is a heterotrimer of pro-alpha chains derived from three distinct genes-COL9A1, COL9A2, and COL9A3 [10].

Chemical compound and disease context of COL9A2

• Treatment of medulloblastoma (Daoy and D283 MED) and glioma (U-251MG, C6, and RG2) cell lines resulted in a dose-dependent decline in DNA synthesis and cell proliferation, associated with accumulation in the G0/G1 phase of the cell cycle [11].

Biological context of COL9A2

• The second locus, EDM2, maps to chromosome 1, in a region spanning COL9A2 [9].
• The COL9A2 gene is only about 15 kb, and it contains 32 exons [12].
• Localization of the COL9A2 gene to human chromosome 1 was subsequently performed using a panel of DNAs from human/rodent somatic cell hybrids [13].
• Mutation screening of candidate regions revealed a novel point mutation at position -1 in the COL9A2 exon 3/intron 3 splicing region [14].
• To illustrate the utility of this method, we showed that the gene for receptor tyrosine kinase TIE lies centromeric to COL9A2, RLF, and L-MYC genes at 1p32 [15].

Associations of COL9A2 with chemical compounds

• Previously, a dominantly inherited defect was identified in the COL9A2 gene that changed a codon for glutamine to that for tryptophan in the alpha2 chain of collagen IX (Trp2 allele) [16].

Other interactions of COL9A2

• Here we report the complete structure for the human COL9A1 and the complete sequence for the human COL9A2 genes [12].
• Linkage to candidate genes COL9A1, COL9A2, and COL11A2 was tested and excluded for both genetic models in this family [17].
• Using this family, we have identified an MED locus on the short arm of chromosome 1, in a region containing the gene (COL9A2) that encodes the alpha 2 chain of type IX collagen, a structural component of the cartilage extracellular matrix [18].
• In a Finnish population, a single nucleotide polymorphism (SNP) causing an amino-acid substitution (Trp2 allele) in COL9A2, which encodes the alpha2 (IX) chain of type IX collagen, has been reported to associate with LDD [19].
• The relationship between the COL9A2 gene polymorphism and clinical manifestations of RA was evaluated [20].

Analytical, diagnostic and therapeutic context of COL9A2

• Molecular cloning of the human alpha 2(IX) collagen cDNA and assignment of the human COL9A2 gene to chromosome 1 [13].
• COL9A2 was mapped to human chromosome 1p32.3-p33 using fluorescence in situ hybridization [21].

References