Colocalization of the genes for the α3(IV) and α4(IV) chains of type IV collagen to chromosome 2 bands q35–q37

Abstract

Each type of basement membrane in man contains between two and five genetically distinct type IV collagens: α1(IV)–α5(IV). Genes for α1(IV), α2(IV), α3(IV), and α5(IV) have been isolated. We have recently isolated partial cDNAs for the fifth member of the family, designated α4(IV). On the basis of comparison of the deduced peptide sequences of all five chains, the type IV collagens can be divided into two families: α1-like, comprising α1(IV), α3(IV), and α5(IV); and α2-like, comprising α2(IV) and α4(IV). Genes encoding the α1(IV) and α2(IV) chains (COL4A1 and COL4A2) both map to human chromosome 13q34 and have been shown to be transcribed from opposite DNA strands using a common bidirectional promoter that allows coordinate regulation of the two chains. Indeed, these two chains are commonly found together in basement membrane and form [ α1] 2·[ α2] heterotrimers. Whereas α1(IV) and α2(IV) have been found in all basement membranes studied hitherto, it has been shown that α3(IV) and α4(IV) are found in only a subset of basement membranes. In basement membranes where either of these molecules is present, however, they are found together. In view of this relationship and the structural similarities between α1(IV) and α3(IV) and between α2(IV) and α4(IV), we hypothesized that COL4A3 and COL4A4, the genes encoding α3(IV) and α4(IV), respectively, have a genomic organization similar to that of COL4A1 and COL4A2. As a first test of this hypothesis we decided to determine whether COL4A3 and COL4A4 map to the same region of the human genome. We have previously shown that COL4A3 maps to chromosome 2 band q35–q37. Here we show, by somatic cell hybrid analysis and in situ hybridization, that COL4A4 colocalizes with COL4A3. Further experiments will be required to determine the genomic organization of these genes.