• 1
    Seldin MF, Amos CI, Ward R, Gregersen PK. The genetics revolution and the assault on rheumatoid arthritis. Arthritis Rheum 1999; 42: 10719.
  • 2
    MacGregor AJ, Snieder H, Rigby AS, Koskenvuo M, Kaprio J, Aho K, et al. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum 2000; 43: 307.
  • 3
    Jawaheer D, Seldin MF, Amos CI, Chen WV, Shigeta R, Etzel C, et al. Screening the genome for rheumatoid arthritis susceptibility genes: a replication study and combined analysis of 512 multicase families. Arthritis Rheum 2003; 48: 90616.
  • 4
    Jawaheer D, Seldin MF, Amos CI, Chen WV, Shigeta R, Monteiro J, et al. A genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases. Am J Hum Genet 2001; 68: 92736.
  • 5
    Cornelis F, Faure S, Martinez M, Prud'homme JF, Fritz P, Dib C, et al. New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study. Proc Natl Acad Sci U S A 1998; 95: 1074650.
  • 6
    Shiozawa S, Hayashi S, Tsukamoto Y, Goko H, Kawasaki H, Wada T, et al. Identification of the gene loci that predispose to rheumatoid arthritis. Int Immunol 1998; 10: 18915.
  • 7
    MacKay K, Eyre S, Myerscough A, Milicic A, Barton A, Laval S, et al. Whole-genome linkage analysis of rheumatoid arthritis susceptibility loci in 252 affected sibling pairs in the United Kingdom. Arthritis Rheum 2002; 46: 6329.
  • 8
    Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, et al. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet 2003; 34: 395402.
  • 9
    Okamoto K, Makino S, Yoshikawa Y, Takaki A, Nagatsuka Y, Ota M, et al. Identification of IκBL as the second major histocompatibility complex-linked susceptibility locus for rheumatoid arthritis. Am J Hum Genet 2003; 72: 30312.
  • 10
    Cordell HJ. Epistasis: what it means, what it doesn't mean, and statistical methods to detect it in humans. Hum Mol Genet 2002; 11: 24638.
  • 11
    Joe B, Cannon GW, Griffiths MM, Dobbins DE, Gulko PS, Wilder RL, et al. Evaluation of quantitative trait loci regulating severity of mycobacterial adjuvant-induced arthritis in monocongenic and polycongenic rats: identification of a new regulatory locus on rat chromosome 10 and evidence of overlap with rheumatoid arthritis susceptibility loci. Arthritis Rheum 2002; 46: 107585.
  • 12
    Joe B, Remmers EF, Dobbins DE, Salstrom JL, Furuya T, Dracheva S, et al. Genetic dissection of collagen-induced arthritis in chromosome 10 quantitative trait locus speed congenic rats: evidence for more than one regulatory locus and sex influences. Immunogenetics 2000; 51: 93044.
  • 13
    Remmers EF, Joe B, Griffiths MM, Dobbins DE, Dracheva SV, Hashiramoto A, et al. Modulation of multiple experimental arthritis models by collagen-induced arthritis quantitative trait loci isolated in congenic rat lines: different effects of non–major histocompatibility complex quantitative trait loci in males and females. Arthritis Rheum 2002; 46: 222534.
  • 14
    Adarichev VA, Nesterovitch AB, Bardos T, Biesczat D, Chandrasekaran R, Vermes C, et al. Sex effect on clinical and immunologic quantitative trait loci in a murine model of rheumatoid arthritis. Arthritis Rheum 2003; 48: 170820.
  • 15
    Vingsbo-Lundberg C, Nordquist N, Olofsson P, Sundvall M, Saxne T, Pettersson U, et al. Genetic control of arthritis onset, severity and chronicity in a model for rheumatoid arthritis in rats. Nat Genet 1998; 20: 4014.
  • 16
    Remmers EF, Longman RE, Du Y, O'Hare A, Cannon GW, Griffiths MM, et al. A genome scan localizes five non-MHC loci controlling collagen-induced arthritis in rats. Nat Genet 1996; 14: 825.
  • 17
    Gulko PS, Kawahito Y, Remmers EF, Reese VR, Wang J, Dracheva SV, et al. Identification of a new non–major histocompatibility complex genetic locus on chromosome 2 that controls disease severity in collagen-induced arthritis in rats. Arthritis Rheum 1998; 41: 212231.
  • 18
    Lorentzen JC, Glaser A, Jacobsson L, Galli J, Fakhrai-rad H, Klareskog L, et al. Identification of rat susceptibility loci for adjuvant-oil-induced arthritis. Proc Natl Acad Sci U S A 1998; 95: 63837.
  • 19
    Otto JM, Chandrasekeran R, Vermes C, Mikecz K, Finnegan A, Rickert SE, et al. A genome scan using a novel genetic cross identifies new susceptibility loci and traits in a mouse model of rheumatoid arthritis. J Immunol 2000; 165: 527886.
  • 20
    Otto JM, Cs-Szabo G, Gallagher J, Velins S, Mikecz K, Buzas EI, et al. Identification of multiple loci linked to inflammation and autoantibody production by a genome scan of a murine model of rheumatoid arthritis. Arthritis Rheum 1999; 42: 252431.
  • 21
    Olofsson P, Lu S, Holmberg J, Song T, Wernhoff P, Pettersson U, et al. A comparative genetic analysis between collagen-induced arthritis and pristane-induced arthritis. Arthritis Rheum 2003; 48: 233242.
  • 22
    Olofsson P, Wernhoff P, Holmberg J, Holmdahl R. Two-loci interaction confirms arthritis-regulating quantitative trait locus on rat chromosome 6. Genomics 2003; 82: 6529.
  • 23
    Wester L, Olofsson P, Ibrahim SM, Holmdahl R. Chronicity of pristane-induced arthritis in rats is controlled by genes on chromosome 14. J Autoimmun 2003; 21: 30513.
  • 24
    Griffiths MM, Cannon GW, Leonard PA, Reese VR. Induction of autoimmune arthritis in rats by immunization with homologous rat type II collagen is restricted to the RT1av1 haplotype. Arthritis Rheum 1993; 36: 2548.
  • 25
    Kawahito Y, Cannon G, Gulko P, Remmers E, Longman R, Reese V, et al. Localization of quantitative trait loci regulating adjuvant induced arthritis in rats: evidence for genetic factors common to multiple autoimmune diseases. J Immunol 1998; 161: 44119.
  • 26
    Griffiths MM, Cremer MA, Harper DS, McCall S, Cannon GW. Immunogenetics of collagen-induced arthritis in rats: both MHC and non-MHC gene products determine the epitope specificity of immune response to bovine and chick type II collagens. J Immunol 1992; 149: 30916.
  • 27
    Griffiths MM, DeWitt CW. Genetic control of collagen-induced arthritis in rats: the immune response to type II collagen among susceptible and resistant strains and evidence for multiple gene control. J Immunol 1984; 132: 28306.
  • 28
    Wilder RL, Remmers EF, Wilder JM, Dobbins D, Dracheva T, Hashiramoto A, et al. National Institute of Arthritis and Musculoskeletal and Skin Diseases, Arthritis and Rheumatism Branch, Rat Genetic Database. URL:
  • 29
    Pasko D. Rat Genome Database. URL:
  • 30
    Remmers E, Goldmuntz E, Zha H, Crofford L, Cash J, Mathern P. Linkage map of seven polymorphic markers on rat chromosome 18. Mam Genome 1993; 4: 26570.
  • 31
    Lander ES, Green P, Abrahamson J, Barlow A, Daly MJ, Lincoln SE, et al. MapMaker: an interactive computer package for constructing primary genetic linkage maps of experimental and natural populations. Genomics 1987; 1: 17481.
  • 32
    Lincoln SE, Lander ES. Systematic detection of errors in genetic linkage data. Genomics 1992; 14: 60410.
  • 33
    Bihoreau MT, Gauguier D, Kato N, Hyne G, Lindpaintner K, Rapp JP, et al. A linkage map of the rat genome derived from three F2 crosses. Genome Res 1997; 7: 43440.
  • 34
    Jacob HJ, Brown DM, Bunker RK, Daly MJ, Dzau VJ, Goodman A, et al. A genetic linkage map of the laboratory rat, Rattus norvegicus. Nat Genet 1995; 9: 639.
  • 35
    Brown DM, Matise TC, Koike G, Simon JS, Winer ES, Zangen S, et al. An integrated genetic linkage map of the laboratory rat. Mamm Genome 1998; 9: 52130.
  • 36
    Serikawa T, Kuramoto T, Hilbert P, Mori M, Yamada J, Dubay CJ, et al. Rat gene mapping using PCR-analyzed microsatellites. Genetics 1992; 131: 70121.
  • 37
    Lander E, Botstein D. Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 1989; 21: 18599.
  • 38
    Darvasi A. The effect of selective genotyping on QTL mapping accuracy. Mamm Genome 1997; 8: 678.
  • 39
    Lincoln S, Daly M, Lander E. Mapping genes controlling quantitative traits with MapMaker/QTL 1.1. The Whitehead Institute Technical Report. 2nd ed. Cambridge (MA): The Whitehead Institute; 1992.
  • 40
    Paterson AH, Lander ES, Hewitt JD, Peterson S, Lincoln SE, Tanksley SD. Resolution of quantitative traits into Mendelian factors by using a complete linkage map of restriction fragment length polymorphisms. Nature 1988; 335: 7216.
  • 41
    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: 2532.
  • 42
    Dahlman I, Wallstrom E, Weissert R, Storch M, Kornek B, Jacobsson L, et al. Linkage analysis of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in the rat identifies a locus controlling demyelination on chromosome 18. Hum Mol Genet 1999; 8: 218390.
  • 43
    Becker KG, Simon RM, Bailey-Wilson JE, Freidlin B, Biddison WE, McFarland HF, et al. Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases. Proc Natl Acad Sci U S A 1998; 95: 997984.
  • 44
    Merriman TR, Cordell HJ, Eaves IA, Danoy PA, Coraddu F, Barber R, et al. Suggestive evidence for association of human chromosome 18q12-q21 and its orthologue on rat and mouse chromosome 18 with several autoimmune diseases. Diabetes 2001; 50: 18494.
  • 45
    Furuya T, Salstrom JL, McCall-Vining S, Cannon GW, Joe B, Remmers EF, et al. Genetic dissection of a rat model for rheumatoid arthritis: significant gender influences on autosomal modifier loci. Hum Mol Genet 2000; 9: 224150.
  • 46
    Bateson W. Mendel's principles of heredity. Cambridge: Cambridge University Press; 1909.
  • 47
    Dracheva SV, Remmers EF, Gulko PS, Kawahito Y, Longman RE, Reese VR, et al. Identification of a new quantitative trait locus on chromosome 7 controlling disease severity of collagen-induced arthritis in rats. Immunogenetics 1999; 49: 78791.
  • 48
    Wernhoff P, Olofsson P, Holmdahl R. The genetic control of rheumatoid factor production in a rat model of rheumatoid arthritis. Arthritis Rheum 2003; 48: 358496.
  • 49
    Olofsson P, Nordquist N, Vingsbo-Lundberg C, Larsson A, Falkenberg C, Pettersson U, et al. Genetic links between the acute-phase response and arthritis development in rats. Arthritis Rheum 2002; 46: 25968.
  • 50
    Holm BC, Wei Xu H, Jacobsson L, Larsson A, Luthman H, Lorentzen JC. Rats made congenic for Oia3 on chromosome 10 become susceptible to squalene-induced arthritis. Hum Mol Genet 2001; 10: 56572.
  • 51
    Barton A, Eyre S, Myerscough A, Brintnell B, Ward D, Ollier WE, et al. High resolution linkage and association mapping identifies a novel rheumatoid arthritis susceptibility locus homologous to one linked to two rat models of inflammatory arthritis. Hum Mol Genet 2001; 10: 19016.
  • 52
    Wilder R, Remmers E, Kawahito Y, Gulko P, Cannon G, Griffiths M. Genetic factors regulating experimental arthritis in mice and rats. In: TheophilopoulosA, editor. Current directions in autoimmunity. Basel: Karger; 1999. p. 12165.
  • 53
    Holmdahl R, Vingsbo C, Malmstrom V, Jansson L, Holmdahl M. Chronicity of arthritis induced with homologous type II collagen (CII) in rats is associated with anti-CII B-cell activation. J Autoimmun 1994; 7: 73952.
  • 54
    Griffiths MM, Wang J, Joe B, Dracheva S, Kawahito Y, Shepard JS, et al. Identification of four new quantitative trait loci regulating arthritis severity and one new quantitative trait locus regulating autoantibody production in rats with collagen-induced arthritis. Arthritis Rheum 2000; 43: 127889.
  • 55
    Adarichev VA, Valdez JC, Bardos T, Finnegan A, Mikecz K, Glant TT. Combined autoimmune models of arthritis reveal shared and independent qualitative (binary) and quantitative trait loci. J Immunol 2003; 170: 228392.
  • 56
    Listwak S, Barrientos RM, Koike G, Ghosh S, Gomez M, Misiewicz B, et al. Identification of a novel inflammation-protective locus in the Fischer rat. Mamm Genome 1999; 10: 3625.
  • 57
    Klaff LS, Koike G, Jiang J, Wang Y, Bieg S, Pettersson A, et al. BB rat diabetes susceptibility and body weight regulation genes colocalize on chromosome 2. Mamm Genome 1999; 10: 8837.
  • 58
    Lander E, Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 1995; 11: 2417.
  • 59
    Olofsson P, Holmberg J, Pettersson U, Holmdahl R. Identification and isolation of dominant susceptibility loci for pristane-induced arthritis. J Immunol 2003; 171: 40716.
  • 60
    Sun SH, Silver PB, Caspi RR, Du Y, Chan CC, Wilder RL, et al. Identification of genomic regions controlling experimental autoimmune uveoretinitis in rats. Int Immunol 1999; 11: 52934.
  • 61
    Bergsteinsdottir K, Yang HT, Pettersson U, Holmdahl R. Evidence for common autoimmune disease genes controlling onset, severity, and chronicity based on experimental models for multiple sclerosis and rheumatoid arthritis. J Immunol 2000; 164: 15648.
  • 62
    Kloting I, Vogt L, Serikawa T. Locus on chromosome 18 cosegregates with diabetes in the BB/OK rat subline. Diabetes Metab 1995; 21: 33844.
  • 63
    Weis JJ, McCracken BA, Ma Y, Fairbairn D, Roper RJ, Morrison TB, et al. Identification of quantitative trait loci governing arthritis severity and humoral responses in the murine model of Lyme disease. J Immunol 1999; 162: 94856.
  • 64
    Kono DH, Burlingame RW, Owens DG, Kuramochi A, Balderas RS, Balomenos D, et al. Lupus susceptibility loci in New Zealand mice. Proc Natl Acad Sci U S A 1994; 91: 1016872.
  • 65
    Wu J, Longmate JA, Adamus G, Hargrave PA, Wakeland EK. Interval mapping of quantitative trait loci controlling humoral immunity to exogenous antigens: evidence that non-MHC immune response genes may also influence susceptibility to autoimmunity. J Immunol 1996; 157: 2498505.
  • 66
    Mahler M, Bristol IJ, Sundberg JP, Churchill GA, Birkenmeier EH, Elson CO, et al. Genetic analysis of susceptibility to dextran sulfate sodium-induced colitis in mice. Genomics 1999; 55: 14756.
  • 67
    Baker D, Rosenwasser OA, O'Neill JK, Turk JL. Genetic analysis of experimental allergic encephalomyelitis in mice. J Immunol 1995; 155: 404651.
  • 68
    Blankenhorn EP, Butterfield RJ, Rigby R, Cort L, Giambrone D, McDermott P, et al. Genetic analysis of the influence of pertussis toxin on experimental allergic encephalomyelitis susceptibility: an environmental agent can override genetic checkpoints. J Immunol 2000; 164: 34205.
  • 69
    Gaffney PM, Ortmann WA, Selby SA, Shark KB, Ockenden TC, Rohlf KE, et al. Genome screening in human systemic lupus erythematosus: results from a second Minnesota cohort and combined analyses of 187 sib-pair families. Am J Hum Genet 2000; 66: 54756.
  • 70
    Xu C, Dai Y, Fredrikson S, Hillert J. Association and linkage analysis of candidate chromosomal regions in multiple sclerosis: indication of disease genes in 12q23 and 7ptr-15. Eur J Hum Genet 1999; 7: 1106.
  • 71
    Satsangi J, Parkes M, Louis E, Hashimoto L, Kato N, Welsh K, et al. Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12. Nat Genet 1996; 14: 199202.
  • 72
    Davies JL, Kawaguchi Y, Bennett ST, Copeman JB, Cordell HJ, Pritchard LE, et al. A genome-wide search for human type 1 diabetes susceptibility genes. Nature 1994; 371: 1306.
  • 73
    Shai R, Quismorio FP Jr, Li L, Kwon OJ, Morrison J, Wallace DJ, et al. Genome-wide screen for systemic lupus erythematosus susceptibility genes in multiplex families. Hum Mol Genet 1999; 8: 63944.
  • 74
    Tienari PJ, Wikstrom J, Sajantila A, Palo J, Peltonen L. Genetic susceptibility to multiple sclerosis linked to myelin basic protein gene. Lancet 1992; 340: 98791.
  • 75
    Merriman T, Twells R, Merriman M, Eaves I, Cox R, Cucca F, et al. Evidence by allelic association-dependent methods for a type 1 diabetes polygene (IDDM6) on chromosome 18q21. Hum Mol Genet 1997; 6: 100310.
  • 76
    Vaidya B, Imrie H, Perros P, Young ET, Kelly WF, Carr D, et al. Evidence for a new Graves disease susceptibility locus at chromosome 18q21. Am J Hum Genet 2000; 66: 17104.
  • 77
    Yamada R, Tanaka T, Unoki M, Nagai T, Sawada T, Ohnishi Y, et al. Association between a single-nucleotide polymorphism in the promoter of the human interleukin-3 gene and rheumatoid arthritis in Japanese patients, and maximum-likelihood estimation of combinatorial effect that two genetic loci have on susceptibility to the disease. Am J Hum Genet 2001; 68: 67485.