Assignment of a type I collagen structural gene to human chromosome 7

Abstract

COLLAGEN is the major extracellular protein of the body, and forms the fibres which impart tensile strength to all of its structural elements, including skin, bone, tendon and cartilage. It occurs as a family of molecules with closely related structures but distinctive tissue distributions¹. Four types have been described with varying degrees of precision; the most abundant and best studied (type I) is a heteropolymer of three polypeptides, two identical (α₁(I)), and a third (α₂(I)) which differs slightly in primary structure. Types II-IV are homopolymers of the general formula (α₁(X))₃, where the designation α₁ reflects the close sequence homologies shared with α₁(I), although this relationship is only tentative in the case of α₁(IV). These collagens are probably the products of at least five non-allelic structural genes, and knowledge of their linkage would be useful in view of their possible origin by duplication and divergence from an ancestral collagen gene. Quantitative variations in the expression of these genes are important in normal tissue development, and defective expression has been implied in two inherited disorders, Ehlers-Danlos IV² and osteogenesis imperfecta³. The chromosomal assignment of these structural genes is a first step towards discovering their linkage relationship and perhaps towards understanding more about their differential expression. Because collagen is readily synthesised by cells in vitro, the problem of chromosome assignments may be investigated by the techniques of somatic cell genetics. When mouse and human cells are fused, random loss of human chromosomes occur, while the full set of mouse chromosomes is usually retained. Assignment of a gene to the chromosome carrying it can be achieved by examining sets of hybrids for expression of the human gene product and ascertaining the segregation of this phenotype with a particular human chromosome. We have examined a series of human–mouse hybrid clones for the production of collagen and report here the consistent segregation of human collagen with human chromosome 7.