Regional localization of the human Rα2(I) collagen gene on chromosome 7 by molecular hybridization

The multigene procollagen family encodes probably >20 genetically distinct but structurally related polypeptide chains. Recent characterization of human procollagen clones has allowed determination of functional domains within the proteins, genomic organization, and chromosomal location. Previously, we assigned the coordinately expressed type I genes (al and a2) to chromosomes 17 and 7, respectively, and now other investigators have mapped the type II gene to chromosome 12 [Strom, C. M., Eddy, R. L. & Shows, T. B. (1984) Somatic CeU Genet. 10, 651-655]. Recently, we isolated cDNA clones encoding the fourth interstitial procollagen, type III, and the a2 chain of the type V cytoskeletal components. To determine whether these genes were clustered with al(I), a2(I), or al(II) or were further dispersed in the genome, in situ hybridization of the a1(Ill) and a2(V) probes to metaphase chromosomes was carried out. Here we report a fourth autosome with procollagen gene loci but the first cytological evidence for linkage. By using normal and translocated cell lines, our results show that both the ail(llI) and a2(V) procollagen genes map to the q24.3--q31 region of chromosome 2.The procollagens constitute a group of proteins responsible for the structural integrity of connective tissue (see refs. 1-4 for reviews). The polypeptide chains are generally composed of a large collagenous domain with the repeating Gly-X-Y sequence flanked by smaller amino-and carboxyl-extension peptides. More than five major and five minor types of collagen have been identified, which consist of one, two, or three different chains folded into a triple-helical molecule (1-9). While several types have a unique tissue distribution (II in cartilage and IV in basement membrane), others (I, III, and V) are usually coexpressed but at different levels depending on the cell type (1-4). We have been studying the structure and regulation of these latter three collagens normally found together in the proportion I > III > V. Whereas type I is the major collagen species in skin, bone, tendon, placenta, lung, and liver, type III appears to predominate in blood vessels and internal organs (1-4, 10, 11). Little is currently known about the minor component, type V, except for its distribution in pericellular regions (12).Isolation of DNA clones encoding different procollagen chains has allowed determination of the amino acid sequence, genomic organization, and chromosomal assignment (see refs. 4 and 13 for reviews). For example, the sizes of the al(I) and a2(I) genes (13-15) are inversely proportional to the 2:1 ratio of the mRNAs in cultured fibroblasts, reflecting the subunit composition of type I collagen (16). Interestingly, these two carefully regulated coding units, both interrupted by -50 introns, are located on the long arm of chromosomes 17 and 7, respectively, as determined from somatic cell and in situ hybridization (17)(18)(19)(20). Since the collagens seem to have arisen by duplication of a 54-base-pair (bp) primordial unit (21), it had been ...

mentioning

confidence: 99%

Human alpha 1(III) and alpha 2(V) procollagen genes are located on the long arm of chromosome 2.

Emanuel¹,

Cannizzaro²,

Seyer³

et al. 1985

“…4 contains chromosomes 7 and 13 as its only karyotypically visible human material. Hybrid C121 (track 2) contains chromosome 7 as its only human material and is clearly negative, suggesting that the gene coding for the al(IV) gene is on chromosome 13 and not on chromosome 7 with the a2(I) gene. Hybrid PCTBA1.8 (Table 1) contains chromosome 17 as its only human material and is negative, so the al(IV) gene is not on the same chromosome as the al(I) gene.…”

Section: Resultsmentioning

confidence: 99%

“…It has been known for some time that in humans the genes for the two chains of type I are not on the same chromosome; the al(I) chain is coded for by a gene, COLIAI, on chromosome 17 (11)(12)(13), whereas the a2(I) gene, COLJA2, is on chromosome 7 (14,15). In this paper we present evidence that the genes encoding type II collagen (COL2AJ), type III collagen (COL3AJ), and al(IV) collagen (COL4A]) are on different chromosomes and not in a cluster on chromosome 7 or 17.…”

mentioning

confidence: 99%

Chromosomal assignments of the genes coding for human types II, III, and IV collagen: a dispersed gene family.

Solomon¹,

Hiorns²,

Spurr³

et al. 1985

The human type II collagen gene, COL2A1, has been assigned to chromosome 12, the type III gene, COL3AI, to chromosome 2, and one of the type IV genes, COMA), to chromosome 13. These assignments were made by using cloned genes as probes on Southern blots of DNA from a panel of mouse/human somatic cell hybrids. The two genes of type I collagen, COLIAI and COL2AI, have been mapped previously to chromosomes 17 and 7, respectively. This family of conserved genes seems therefore to be dispersed throughout the genome.In vertebrates, the family of collagen proteins consists of a minimum of nine types of collagen molecules whose constituent chains are coded for by a minimum of 17 genes (1-5). Types I, II, and III, the so-called interstitial collagens, are the best characterized in terms of the amino acid and DNA sequences of their chains, and these data suggest that these chains are highly conserved evolutionarily. The genes coding for the interstitial chains have been isolated from several species and exhibit a very unusual and characteristic structure of a large number of relatively small exons [54 and 108 base pairs (bp)] at conserved positions along the length of the triple-helical Gly-X-Y portion (see ref. 6 for review). Type I collagen is a heteropolymer of two al(I) chains and one a2(I) chain, whereas types II and III are homopolymers of three al(II) and al(III) chains, respectively. These three interstitial collagen molecules each form highly ordered fibrils and are responsible for the tensile strength of tissue such as skin, bone, tendon (types I and III), and hyaline cartilage (type II) in which they are found.

“…Finding a fifth chromosome with collagen gene loci was not surprising since even the genes encoding the structurally related types I (al and a2), II, III, and a2(V) chains are almost entirely dispersed (29,(31)(32)(33)(34)(35)(36). The type I genes, al and a2, are present on chromosomes 17 (32,33) and 7 (31,34), respectively, and the al(II) gene is located on chromosome 12 (29,35). Of the collagen genes mapped to date, only the al(III) and a2(V) genes are known to share the same genomic site-i.e., the q24.3-*q31 region of chromosome 2 (36).…”

mentioning

confidence: 99%

Human collagen genes encoding basement membrane alpha 1 (IV) and alpha 2 (IV) chains map to the distal long arm of chromosome 13.

Griffin¹,

Emanuel²,

Hansen³

et al. 1987

At least 20 genes encode the structurally related collagen chains that comprise >10 homo-or heterotrimeric types. Six members of this multigene family have been assigned to five chromosomes in the human genome. The two type I genes, al and a2, are located on chromosomes 17 and 7, respectively, and the al(ll) gene is located on chromosome 12. Our recent mapping of the al(llI) and a2(V) genes to the q24.3-*q31 region of chromosome 2 provided the only evidence that the collagen genes are not entirely dispersed. To further determine their organization, we and others localized the al(IV) gene to chromosome 13 and in our experiments sublocalized the gene to band q34 by in situ hybridization. Here we show the presence of the ci2 type IV locus also on the distal long arm of chromosome 13 by hybridizing a human a2(IV) cDNA clone to rodent-human hybrids and to metaphase chromosomes. To our knowledge, these studies represent the only demonstration of linkage between genes encoding both polypeptide chains of the same collagen type.