Intron-mediated recombination may cause a deletion in an alpha 1 type I collagen chain in a lethal form of osteogenesis imperfecta.

Publisher Website
Google Scholar
Abstract
To understand the nature of the mutation in type I collagen genes in cells from an infant with the perinatal lethal form of osteogenesis imperfecta (type II), almost 2 kilobases of a normal .alpha.1(I) collagen gene and the corresponding region of a mutant .alpha.1(I) gene from cell strain CRL 1262 were cloned and sequenced. The mutant gene had undergone recombination between 2 non-homologous introns, which resulted in the loss of 3 exons coding for 84 amino acids in the triple-helical domain. The deletion predicted the loss of amino acid residues surrounding and including the Met at the junction between the CNBr peptides .alpha.1(I) CB8 and .alpha.1(I) CB3, a result confirmed by analysis of the cleavage peptides from the product of the mutant gene. Although large deletions form collagen genes are uncommon causes of the osteogenesis imperfecta type II phenotype, analysis of the de novo change in gene structure in this cell strain suggests that similar rearrangements may have occurred during the evolution of the large collagen genes.