Completion of the intron-exon structure of the gene for human type II procollagen (COL2A1): variations in the nucleotide sequences of the alleles from three chromosomes.

A new procedure for preparing cosmid libraries was used to isolate three alleles for the human gene for type II procollagen (COL2A1). Over 20,000 bp of one allele were completely sequenced and over 10,000 bp of the two other alleles were sequenced. The data located and defined 26 exons and introns of the gene not previously analyzed. The results completed the structure of the gene except for the newly discovered exon 2A that undergoes alternative splicing (Ryan et al., 1990, Trans. Ann. Meet. Orthop. Res. Soc. 15:65). As a result, it is the most completely known structure of a gene for a human fibrillar collagen. The results confirm the previous impression that exon sizes are highly conserved among the genes for the three major fibrillar collagens. Comparison of clones from the three alleles defined five neutral variations in coding sequences and seven variations in the intron that also are probably neutral variations. The normal sequences and the variations in sequences will be important for identifying different alleles and haplotypes of the gene and for the analysis of genetic mutations in the gene that cause diseases of cartilage such as chondrodysplasias and osteoarthritis.