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Published in: Arthritis Research & Therapy 3/2005

Open Access 01-03-2005 | Research article

A web tool for finding gene candidates associated with experimentally induced arthritis in the rat

Authors: Lars Andersson, Greta Petersen, Per Johnson, Fredrik Ståhl

Published in: Arthritis Research & Therapy | Issue 3/2005

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Abstract

Rat models are frequently used for finding genes contributing to the arthritis phenotype. In most studies, however, limitations in the number of animals result in a low resolution. As a result, the linkage between the autoimmune experimental arthritis phenotype and the genomic region, that is, the quantitative trait locus, can cover several hundred genes. The purpose of this work was to facilitate the search for candidate genes in such regions by introducing a web tool called Candidate Gene Capture (CGC) that takes advantage of free text data on gene function. The CGC tool was developed by combining genomic regions in the rat, associated with the autoimmune experimental arthritis phenotype, with rat/human gene homology data, and with descriptions of phenotypic gene effects and selected keywords. Each keyword was assigned a value, which was used for ranking genes based on their description of phenotypic gene effects. The application was implemented as a web-based tool and made public at http://​ratmap.​org/​cgc. The CGC application ranks gene candidates for 37 rat genomic regions associated with autoimmune experimental arthritis phenotypes. To evaluate the CGC tool, the gene ranking in four regions was compared with an independent manual evaluation. In these sample tests, there was a full agreement between the manual ranking and the CGC ranking for the four highest-ranked genes in each test, except for one single gene. This indicates that the CGC tool creates a ranking very similar to that made by human inspection. The exceptional gene, which was ranked as a gene candidate by the CGC tool but not in the manual evaluation, was found to be closely associated with rheumatoid arthritis in additional literature studies. Genes ranked by the CGC tools as less likely gene candidates, as well as genes ranked low, were generally rated in a similar manner to those done manually. Thus, to find genes contributing to experimentally induced arthritis, we consider the CGC application to be a helpful tool in facilitating the evaluation of large amounts of textual information.
Literature
1.
go back to reference Felson DT: Epidemiology of rheumatic diseases. Arthritis and Allied Conditions – A Textbook of Rheumatology. Edited by: Koopman WJ. 1997, Baltimore, MD: Williams & Williams, 3-10. Felson DT: Epidemiology of rheumatic diseases. Arthritis and Allied Conditions – A Textbook of Rheumatology. Edited by: Koopman WJ. 1997, Baltimore, MD: Williams & Williams, 3-10.
2.
go back to reference Wilder RL: Rheumatoid arthritis: epidemiology, pathology, and pathogenesis. Primer on the Rheumatic Diseases. Edited by: Schumacher HR Jr, Klippel JH, Koopman WJ. 1993, Atlanta: Arthritis Foundation, 86-89. 10 Wilder RL: Rheumatoid arthritis: epidemiology, pathology, and pathogenesis. Primer on the Rheumatic Diseases. Edited by: Schumacher HR Jr, Klippel JH, Koopman WJ. 1993, Atlanta: Arthritis Foundation, 86-89. 10
3.
go back to reference Deighton CM, Walker DJ, Griffiths ID, Roberts DF: The contribution of HLA to rheumatoid arthritis. Clin Genet. 1989, 36: 178-182.CrossRefPubMed Deighton CM, Walker DJ, Griffiths ID, Roberts DF: The contribution of HLA to rheumatoid arthritis. Clin Genet. 1989, 36: 178-182.CrossRefPubMed
4.
go back to reference Wilder RL, Griffiths MM, Cannon GW, Caspi R, Remmers EF: Susceptibility to autoimmune disease and drug addiction in inbred rats. Are there mechanistic factors in common related to abnormalities in hypothalamic–pituitary–adrenal axis and stress response function?. Ann NY Acad Sci. 2000, 917: 784-796.CrossRefPubMed Wilder RL, Griffiths MM, Cannon GW, Caspi R, Remmers EF: Susceptibility to autoimmune disease and drug addiction in inbred rats. Are there mechanistic factors in common related to abnormalities in hypothalamic–pituitary–adrenal axis and stress response function?. Ann NY Acad Sci. 2000, 917: 784-796.CrossRefPubMed
5.
go back to reference Griffiths MM, Remmers EF: Genetic analysis of collagen-induced arthritis in rats: a polygenic model for rheumatoid arthritis predicts a common framework of cross-species inflammatory/autoimmune disease loci. Immunol Rev. 2001, 184: 172-183. 10.1034/j.1600-065x.2001.1840116.x.CrossRefPubMed Griffiths MM, Remmers EF: Genetic analysis of collagen-induced arthritis in rats: a polygenic model for rheumatoid arthritis predicts a common framework of cross-species inflammatory/autoimmune disease loci. Immunol Rev. 2001, 184: 172-183. 10.1034/j.1600-065x.2001.1840116.x.CrossRefPubMed
6.
go back to reference Holmdahl R: Dissection of the genetic complexity of arthritis using animal models. J Autoimmun. 2003, 21: 99-103. 10.1016/S0896-8411(03)00096-9.CrossRefPubMed Holmdahl R: Dissection of the genetic complexity of arthritis using animal models. J Autoimmun. 2003, 21: 99-103. 10.1016/S0896-8411(03)00096-9.CrossRefPubMed
12.
go back to reference Khani-Hanjani A, Lacaille D, Hoar D, Chalmers A, Horsman D, Anderson M, Balshaw R, Keown PA: Association between dinucleotide repeat in non-coding region of interferon-gamma gene and susceptibility to, and severity of, rheumatoid arthritis. Lancet. 2000, 356: 820-825. 10.1016/S0140-6736(00)02657-X.CrossRefPubMed Khani-Hanjani A, Lacaille D, Hoar D, Chalmers A, Horsman D, Anderson M, Balshaw R, Keown PA: Association between dinucleotide repeat in non-coding region of interferon-gamma gene and susceptibility to, and severity of, rheumatoid arthritis. Lancet. 2000, 356: 820-825. 10.1016/S0140-6736(00)02657-X.CrossRefPubMed
13.
go back to reference Xie MH, Aggarwal S, Ho WH, Foster J, Zhang Z, Stinson J, Wood WI, Goddard AD, Gurney AL: Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R. J Biol Chem. 2000, 275: 31335-31339. 10.1074/jbc.M005304200.CrossRefPubMed Xie MH, Aggarwal S, Ho WH, Foster J, Zhang Z, Stinson J, Wood WI, Goddard AD, Gurney AL: Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R. J Biol Chem. 2000, 275: 31335-31339. 10.1074/jbc.M005304200.CrossRefPubMed
14.
go back to reference Krause A, Scaletta N, Ji JD, Ivashkiv LB: Rheumatoid arthritis synoviocyte survival is dependent on Stat3. J Immunol. 2002, 169: 6610-6616.CrossRefPubMed Krause A, Scaletta N, Ji JD, Ivashkiv LB: Rheumatoid arthritis synoviocyte survival is dependent on Stat3. J Immunol. 2002, 169: 6610-6616.CrossRefPubMed
15.
go back to reference Chen F, Castranova V, Shi X, Demers LM: New insights into the role of nuclear factor-kappa-B, a ubiquitous transcription factor in the initiation of diseases. Clin Chem. 1999, 45: 7-17.PubMed Chen F, Castranova V, Shi X, Demers LM: New insights into the role of nuclear factor-kappa-B, a ubiquitous transcription factor in the initiation of diseases. Clin Chem. 1999, 45: 7-17.PubMed
16.
go back to reference Neu E, von Mikecz AH, Hemmerich PH, Peter HH, Fricke M, Deicher H, Genth E, Krawinkel U: Autoantibodies against eukaryotic protein L7 in patients suffering from systemic lupus erythematosus and progressive systemic sclerosis: frequency and correlation with clinical, serological and genetic parameters. The SLE Study Group. Clin Exp Immun. 1995, 100: 198-204.PubMedCentralCrossRefPubMed Neu E, von Mikecz AH, Hemmerich PH, Peter HH, Fricke M, Deicher H, Genth E, Krawinkel U: Autoantibodies against eukaryotic protein L7 in patients suffering from systemic lupus erythematosus and progressive systemic sclerosis: frequency and correlation with clinical, serological and genetic parameters. The SLE Study Group. Clin Exp Immun. 1995, 100: 198-204.PubMedCentralCrossRefPubMed
18.
go back to reference Carter RA, O'Donnell K, Sachthep S, Cicuttini F, Boyd AW, Wicks IP: Characterization of a human synovial cell antigen: VCAM-1 and inflammatory arthritis. Immunol Cell Biol. 2001, 79: 419-428. 10.1046/j.1440-1711.2001.01019.x.CrossRefPubMed Carter RA, O'Donnell K, Sachthep S, Cicuttini F, Boyd AW, Wicks IP: Characterization of a human synovial cell antigen: VCAM-1 and inflammatory arthritis. Immunol Cell Biol. 2001, 79: 419-428. 10.1046/j.1440-1711.2001.01019.x.CrossRefPubMed
19.
go back to reference Gonzalez-Alvaro I, Ortiz AM, Garcia-Vicuna R, Balsa A, Pascual-Salcedo D, Laffon A: Increased serum levels of interleukin-15 in rheumatoid arthritis with long-term disease. Clin Exp Rheumatol. 2003, 21: 639-642.PubMed Gonzalez-Alvaro I, Ortiz AM, Garcia-Vicuna R, Balsa A, Pascual-Salcedo D, Laffon A: Increased serum levels of interleukin-15 in rheumatoid arthritis with long-term disease. Clin Exp Rheumatol. 2003, 21: 639-642.PubMed
20.
go back to reference Kataoka K, Handa H, Nishizawa M: Induction of cellular antioxidative stress genes through heterodimeric transcription factor Nrf2/small Maf by antirheumatic gold(I) compounds. J Biol Chem. 2001, 276: 34074-34081. 10.1074/jbc.M105383200.CrossRefPubMed Kataoka K, Handa H, Nishizawa M: Induction of cellular antioxidative stress genes through heterodimeric transcription factor Nrf2/small Maf by antirheumatic gold(I) compounds. J Biol Chem. 2001, 276: 34074-34081. 10.1074/jbc.M105383200.CrossRefPubMed
21.
go back to reference Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, Delohery T, Chen Y, Mitchell RA, Bucala R: MIF signal transduction initiated by binding to CD74. J Exp Med. 2003, 197: 1467-1476. 10.1084/jem.20030286.PubMedCentralCrossRefPubMed Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, Delohery T, Chen Y, Mitchell RA, Bucala R: MIF signal transduction initiated by binding to CD74. J Exp Med. 2003, 197: 1467-1476. 10.1084/jem.20030286.PubMedCentralCrossRefPubMed
22.
go back to reference Superti-Furga A, Neumann L, Riebel T, Eich G, Steinmann B, Spranger J, Kunze J: Recessively inherited multiple epiphyseal dysplasia with normal stature, club foot, and double layered patella caused by a DTDST mutation. J Med Genet. 1999, 36: 621-624.PubMedCentralPubMed Superti-Furga A, Neumann L, Riebel T, Eich G, Steinmann B, Spranger J, Kunze J: Recessively inherited multiple epiphyseal dysplasia with normal stature, club foot, and double layered patella caused by a DTDST mutation. J Med Genet. 1999, 36: 621-624.PubMedCentralPubMed
23.
go back to reference Hastbacka J, de la Chapelle A, Mahtani MM, Clines G, Reeve-Daly MP, Daly M, Hamilton BA, Kusumi K, Trivedi B, Weaver A: The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping. Cell. 1994, 78: 1073-1087. 10.1016/0092-8674(94)90281-X.CrossRefPubMed Hastbacka J, de la Chapelle A, Mahtani MM, Clines G, Reeve-Daly MP, Daly M, Hamilton BA, Kusumi K, Trivedi B, Weaver A: The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping. Cell. 1994, 78: 1073-1087. 10.1016/0092-8674(94)90281-X.CrossRefPubMed
24.
go back to reference Hastbacka J, Superti-Furga A, Wilcox WR, Rimoin DL, Cohn DH, Lander ES: Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias. Am J Hum Genet. 1996, 58: 255-262.PubMedCentralPubMed Hastbacka J, Superti-Furga A, Wilcox WR, Rimoin DL, Cohn DH, Lander ES: Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias. Am J Hum Genet. 1996, 58: 255-262.PubMedCentralPubMed
25.
go back to reference Superti-Furga A, Hastbacka J, Wilcox WR, Cohn DH, van der Harten HJ, Rossi A, Blau N, Rimoin DL, Steinmann B, Lander ES, et al: Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene. Nat Genet. 1996, 12: 100-102. 10.1038/ng0196-100.CrossRefPubMed Superti-Furga A, Hastbacka J, Wilcox WR, Cohn DH, van der Harten HJ, Rossi A, Blau N, Rimoin DL, Steinmann B, Lander ES, et al: Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene. Nat Genet. 1996, 12: 100-102. 10.1038/ng0196-100.CrossRefPubMed
26.
go back to reference Neeck G, Kluter A, Dotzlaw H, Eggert M: Involvement of the glucocorticoid receptor in the pathogenesis of rheumatoid arthritis. Ann NY Acad Sci. 2002, 966: 491-495.CrossRefPubMed Neeck G, Kluter A, Dotzlaw H, Eggert M: Involvement of the glucocorticoid receptor in the pathogenesis of rheumatoid arthritis. Ann NY Acad Sci. 2002, 966: 491-495.CrossRefPubMed
27.
go back to reference Horneff G, Sack U, Kalden JR, Emmrich F, Burmester GR: Reduction of monocyte-macrophage activation markers upon anti-CD4 treatment: decreased levels of IL-1, IL-6, neopterin and soluble CD14 in patients with rheumatoid arthritis. Clin Exp Immunol. 1993, 91: 207-213.PubMedCentralCrossRefPubMed Horneff G, Sack U, Kalden JR, Emmrich F, Burmester GR: Reduction of monocyte-macrophage activation markers upon anti-CD4 treatment: decreased levels of IL-1, IL-6, neopterin and soluble CD14 in patients with rheumatoid arthritis. Clin Exp Immunol. 1993, 91: 207-213.PubMedCentralCrossRefPubMed
28.
go back to reference Yu S, Nakashima N, Xu BH, Matsuda T, Izumihara A, Sunahara N, Nakamura T, Tsukano M, Matsuyama T: Pathological significance of elevated soluble CD14 production in rheumatoid arthritis: in the presence of soluble CD14, lipopolysaccharides at low concentrations activate RA synovial fibroblasts. Rheumatol Int. 1998, 17: 237-243. 10.1007/s002960050041.CrossRefPubMed Yu S, Nakashima N, Xu BH, Matsuda T, Izumihara A, Sunahara N, Nakamura T, Tsukano M, Matsuyama T: Pathological significance of elevated soluble CD14 production in rheumatoid arthritis: in the presence of soluble CD14, lipopolysaccharides at low concentrations activate RA synovial fibroblasts. Rheumatol Int. 1998, 17: 237-243. 10.1007/s002960050041.CrossRefPubMed
29.
go back to reference Olofsson P, Holmberg J, Tordsson J, Lu S, Akerstrom B, Holmdahl R: Positional identification of Ncf1 as a gene that regulates arthritis severity in rats. Nat Genet. 2003, 33: 25-32. 10.1038/ng1058.CrossRefPubMed Olofsson P, Holmberg J, Tordsson J, Lu S, Akerstrom B, Holmdahl R: Positional identification of Ncf1 as a gene that regulates arthritis severity in rats. Nat Genet. 2003, 33: 25-32. 10.1038/ng1058.CrossRefPubMed
30.
go back to reference van Driel MA, Cuelenaere K, Kemmeren PP, Leunissen JA, Brunner HG: A new web-based data mining tool for the identification of candidate genes for human genetic disorders. Eur J Hum Genet. 2003, 11: 57-63. 10.1038/sj.ejhg.5200918.CrossRefPubMed van Driel MA, Cuelenaere K, Kemmeren PP, Leunissen JA, Brunner HG: A new web-based data mining tool for the identification of candidate genes for human genetic disorders. Eur J Hum Genet. 2003, 11: 57-63. 10.1038/sj.ejhg.5200918.CrossRefPubMed
31.
go back to reference Turner FS, Clutterbuck DR, Semple CA: POCUS: mining genomic sequence annotation to predict disease genes. Genome Biol. 2003, 4: R75-10.1186/gb-2003-4-11-r75.PubMedCentralCrossRefPubMed Turner FS, Clutterbuck DR, Semple CA: POCUS: mining genomic sequence annotation to predict disease genes. Genome Biol. 2003, 4: R75-10.1186/gb-2003-4-11-r75.PubMedCentralCrossRefPubMed
32.
go back to reference Perez-Iratxeta C, Bork P, Andrade MA: Association of genes to genetically inherited diseases using data mining. Nat Genet. 2002, 31: 316-319.PubMed Perez-Iratxeta C, Bork P, Andrade MA: Association of genes to genetically inherited diseases using data mining. Nat Genet. 2002, 31: 316-319.PubMed
Metadata
Title
A web tool for finding gene candidates associated with experimentally induced arthritis in the rat
Authors
Lars Andersson
Greta Petersen
Per Johnson
Fredrik Ståhl
Publication date
01-03-2005
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 3/2005
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar1700

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