Complete nucleotide sequence of the region encompassing the first twenty-five exons of the human proα 1(I) collagen gene (COL1A1)

D’Alessio, Marina; Bernard, Michael P.; Pretorious, Petrus J.; Wet, W de; Ramirez, Francesco

doi:10.1016/0378-1119(88)90013-3

Cited by 82 publications

(20 citation statements)

References 22 publications

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“…COL1A1 and COL1A2 (GDB Accession numbers 119061 and 119062, respectively) are large genes, located on chromosomes 17 and 7, respectively (Sunder Raj et al 1977, Junien et al 1982. Both genes comprise 52 exons distributed over 18 (COL1A1) (D'Alessio et al 1988) and 38 (COL1A2) (de Wet et al 1987) Kb of genomic DNA. Mutations in the genes encoding type I collagen were first described in the early 1980s (Chu et al 1983, Pihlajaniemi et al 1984).…”

Section: Introductionmentioning

confidence: 99%

Thirty-three novel COL1A1 and COL1A2 mutations in patients with osteogenesis imperfecta types I-IV

et al. 2001

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Osteogenesis imperfecta (OI) is a heritable disease of bone characterized by low bone mass and bone fragility. Six different types of OI have been described to date, based on clinical phenotype and histological findings. The genetic defect in many patients with OI types I-IV is due to mutations in the genes encoding type I collagen, while patients with OI types V and VI show no evidence of mutations in the COL1A1/COL1A2 genes. Here we report thirty-three novel mutations in patients with types I-IV OI. Sixteen mutations were in COL1A1 and seventeen were in COL1A2. Most mutations resulted in substitutions for glycine: one of these, a doublet GG>CC transversion, created a unique Gly-->Pro missense mutation in the triple helical domain of COL1A2. Two rare triple helical Gly-->Glu substitutions in COL1A2 are also described. In addition, there were six single-base deletion mutations resulting in frameshifts, seven splice junction mutations, and a 9-bp triple helix insertion associated with a severe (OI II) phenotype. The variety of mutations described in the COL1A1/COL1A2 genes giving rise to an OI phenotype is in accordance with the clinical heterogeneity of the disease. Hum Mutat 17:434, 2001.

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Section: Introductionmentioning

confidence: 99%

Thirty-three novel COL1A1 and COL1A2 mutations in patients with osteogenesis imperfecta types I-IV

et al. 2001

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“…The dominant one was of the ␣1(I) Ctelopeptide (32) beginning at phenylalanine. The second sequence was seven residues in length, at about half the molar yield of the C-telopeptide sequence, and came from the ␣1(I) N-helix cross-linking site at residue 87 (33). The counterpart peptide containing the ␣2(I) chain cross-linking site at residue 87 (34) was not found in any of the DEAE-5PW column fractions ( Fig.…”

Section: Nh 2 -Terminal Proteinmentioning

confidence: 99%

Molecular Site Specificity of Pyridinoline and Pyrrole Cross-links in Type I Collagen of Human Bone

Hanson

Eyre

1996

Journal of Biological Chemistry

166

125

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Compared with soft tissue collagens, bone type I collagen displays a distinctive pattern of covalent cross-linking, with evidence of preferred sites of molecular interaction and a prominence of both immature, divalent crosslinks and mature, trivalent cross-links in the adult tissue. In this study the site-specificity of the mature cross-links in human bone collagen was examined. Peptides containing fluorescent pyridinoline cross-links and Ehrlich's-reactive pyrrole cross-links were isolated from a bacterial collagenase digest of demineralized bone matrix. The digest was fractionated by molecular sieve chromatography, monitoring for peptide absorbance, pyridinoline fluorescence, pyrroles by Ehrlich's reagent, and immunoassay for crosslinked N-telopeptides. Individual cross-linked peptides were resolved by ion-exchange and reverse-phase HPLC. Structures were established by NH 2 -terminal microsequencing, cross-link analysis, electrospray mass spectrometry, and immunoassay. Two, about equally occupied, sites of pyridinoline cross-linking were identified, N-telopeptide to helix and C-telopeptide to helix. Pyrroles were alternative cross-linking products at the same sites, but concen- The chemistry of lysine-mediated intermolecular cross-linking in the fibrillar collagens is understood in some detail (1-4). The three principal collagens, types I, II, and III, have four cross-linking sites at equivalent locations in their molecules, one in each telopeptide and two others at sites in the triplehelical domains at or close to residues 87 and 930. The initial intermolecular cross-links in new fibrils are borohydride-reducible residues that are condensation products between aldehyde side chains formed on the telopeptides by lysyl oxidase, and hydroxylysine or lysine residues in helical domains of adjacent molecules. Both N-telopeptide-to-helix and C-telopeptide-tohelix cross-links occur (5-12). However, as young connective tissues mature, borohydride-reducible cross-links disappear, progressing to more stable, non-reducible compounds (13). The best characterized and most widely distributed mature crosslinks are the fluorescent compound, hydroxylysylpyridinoline (HP) 1 (14) and its deoxy analog, lysylpyridinoline (LP; Ref. 15), also referred to as pyridinoline (Pyr) and deoxypyridinoline (16), respectively. HP is widely distributed in the collagens of most internal, vertebrate connective tissues, whereas LP, although widely distributed, features most prominently in bone and dentin. The pattern of cross-linking in bone collagen is also strikingly different from that of soft tissue collagens in other respects, including retention of a significant pool of the borohydride-reducible, initial cross-links throughout adult life (4). The distinctive pattern of cross-linking interactions in bone collagen may be a result of or, as proposed, a necessary requirement for its mineralization (11,12).In recent years, the pyridinoline residues HP and LP have become widely adopted in clinical studies as urinary markers of bone resorption. The...

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“…Transcription of both genes is up-regulated during fibrogenesis, and their expression is enhanced by a various post-transcriptional regulatory elements. Of particular note is the presence of a stem-loop structure located in the 5Ј-UTR of the two genes (31,32), as well as in the 5Ј-UTR of the ␣1(III) gene (33). This SL encompasses the translation initiation codon (34) and is evolutionarily conserved from sea urchins (35) to zebrafish (36) to chicks (14) to frogs and humans (15), thus implicating a vital role for this structure in collagen gene expression and providing a possible therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

Mutation of the 5′-Untranslated Region Stem-Loop Structure Inhibits α1(I) Collagen Expression in Vivo

Parsons

Stefanovic

Seki

et al. 2011

Journal of Biological Chemistry

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Type I collagen is a heterotrimeric extracellular matrix protein consisting of two ␣1(I) chains and one ␣2(I) chain. During liver fibrosis, activated hepatic stellate cells (HSCs) are the major source of the type I collagen that accumulates in the damaged tissue. Expression of ␣1(I) and ␣2(I) collagen mRNA is increased 60-fold compared with quiescent stellate cells and is due predominantly to post-transcriptional message regulation. Specifically, a stem-loop structure in the 5-untranslated region of ␣1(I) collagen mRNA may regulate mRNA expression in activated HSCs through its interaction with stem-loop binding proteins. The stem-loop may also be necessary for efficient production and folding of the type I collagen heterotrimer. To assess the role of the stem-loop in type I collagen expression in vivo, we generated a knock-in mouse harboring a mutation that abolished the stem-loop structure. Heterozygous and homozygous knock-in mice exhibited a normal phenotype. However, steadystate levels of ␣1(I) collagen mRNA decreased significantly in homozygous mutant MEFs as well as HSCs; intracellular and secreted type I collagen protein levels also decreased. Homozygous mutant mice developed less liver fibrosis. These results confirm an important role of the 5 stem-loop in regulating type I collagen mRNA and protein expression and provide a mouse model for further study of collagen-associated diseases.The collagen family is a group of extracellular matrix proteins involved in a variety of biological processes, including providing structural support to connective tissue and forming the basement membrane of organs (1, 2). Type I collagen is a heterotrimeric protein comprised of two ␣1(I) collagen chains and one ␣2(I) collagen chain, and although located on different chromosomes, these genes are coordinately regulated in a developmental, tissue-specific, and inducible manner (3, 4). The three peptide chains form a triple-helical structure, with several post-translational modifications resulting in multiple inter-and intrachain interactions, providing the protein with increased stability (5, 6). Increased expression and deposition of type I collagen are the most dramatic aspects of liver fibrosis, although expression of other collagens, including type III, is also increased (4). Activated hepatic stellate cells (HSCs) 2 are the major source of type I collagen in the fibrotic liver (7). Expression of type I collagen is very low in quiescent HSCs, which act as a storage site of vitamin A and regulate blood flow through the hepatic sinusoid. However, following a fibrogenic stimulus, HSCs undergo an activation process, characterized by a loss of the vitamin A stores; increased cellular proliferation, migration, and contractility; and increased synthesis of both ␣1(I) and ␣2(I) collagen mRNA and type I collagen protein (8).Type I collagen biosynthesis is a complex process that is regulated at both the transcriptional and post-transcriptional levels. Many of these regulatory processes differ in the quiescent versus activated HSC...

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Complete nucleotide sequence of the region encompassing the first twenty-five exons of the human proα 1(I) collagen gene (COL1A1)

Cited by 82 publications

References 22 publications

Thirty-three novel COL1A1 and COL1A2 mutations in patients with osteogenesis imperfecta types I-IV

Thirty-three novel COL1A1 and COL1A2 mutations in patients with osteogenesis imperfecta types I-IV

Molecular Site Specificity of Pyridinoline and Pyrrole Cross-links in Type I Collagen of Human Bone

Mutation of the 5′-Untranslated Region Stem-Loop Structure Inhibits α1(I) Collagen Expression in Vivo

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