Cloning of human type VII collagen. Complete primary sequence of the alpha 1(VII) chain and identification of intragenic polymorphisms.

Type VII collagen is the major, if not the exclusive, component of the anchoring fibrils, attachment structures at the dermal-epidermal basement membrane zone. In this study, we have isolated overlapping cDNA clones which correspond to full-length human type VII collagen mRNA of approximately 9.2 kilobases. The full-length cDNA sequence contains an 8,833 nucleotide open reading frame encoding 2,944 amino acids. The deduced amino acid sequence revealed the presence of a central collagenous domain flanked by a large NH2-terminal non-collagenous (NC-1) domain which consists of submodules with homology to known adhesive proteins, including nine fibronectin type III-like segments (FNIII), and a smaller COOH-terminal non-collagenous (NC-2) domain. In addition, we report six intragenic polymorphisms in the type VII collagen gene (COL7A1) which can be detected by restriction enzyme digestion of polymerase chain reaction-amplified segments. The complete cDNA sequence and polymorphisms in COL7A1 will facilitate mutational analysis and prenatal diagnosis for patients with the dystrophic forms of epidermolysis bullosa, in which mutations in COL7A1 have been demonstrated.