Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus.

Genetic susceptibility confers significant risk for systemic lupus erythematosus (SLE). The MHC region and other polymorphic loci have been associated with SLE. Because more compelling evidence for an involvement of a genetic locus includes linkage, we tested a candidate region homologous to a murine SLE susceptibility region in 52 SLE-affected sibpairs from three ethnic groups. We analyzed seven microsatellite markers from the human chromosome 1q31-q42 region corresponding to the telomeric end of mouse chromosome 1, the region where specific manifestations of murine lupus, including glomerulonephritis and IgG antichromatin, have been mapped. Comparing the mean allele sharing in affected sibpairs of each of these seven markers to their expected values of 0.50, only the five markers located at 1q41-q42 showed evidence for linkage (P = 0.0005-0.08). Serum levels of IgG antichromatin also showed evidence for linkage to two of these five markers (P = 0.04), suggesting that this phenotype is conserved between mice and humans. Compared to the expected random distribution, the trend of increased sharing of haplotypes was observed in affected sibpairs from three ethnic groups (P < 0.01). We concluded that this candidate 1q41-q42 region probably contains a susceptibility gene(s) that confers risk for SLE in multiple ethnic groups.

[1]  J. Green,et al.  Sibling Method for Detecting HLA-linked genes in disease. , 2008, Tissue antigens.

[2]  B. Hahn.  Antibodies to DNA. , 1998, The New England journal of medicine.

[3]  C. Mohan,et al.  Genetic dissection of SLE pathogenesis. Sle1 on murine chromosome 1 leads to a selective loss of tolerance to H2A/H2B/DNA subnucleosomes. , 1998, The Journal of clinical investigation.

[4]  Leena Peltonen,et al.  A putative vulnerability locus to multiple sclerosis maps to 5p14–p12 in a region syntenic to the murine locus Eae2 , 1996, Nature Genetics.

[5]  John A Todd,et al.  Genetic Analysis of Autoimmune Disease , 1996, Cell.

[6]  W. Sheu,et al.  Quantitative trait locus mapping of human blood pressure to a genetic region at or near the lipoprotein lipase gene locus on chromosome 8p22. , 1996, The Journal of clinical investigation.

[7]  D. Isenberg,et al.  FcγRIIa polymorphism in systemic lupus erythematosus (SLE): no association with disease , 1996 .

[8]  F. Arnett,et al.  Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans. , 1996, The Journal of clinical investigation.

[9]  J. Todd,et al.  Multifactorial inheritance in type 1 diabetes. , 1995, Trends in genetics : TIG.

[10]  C. Kallenberg,et al.  Skewed distribution of IgG Fc receptor IIa (CD32) polymorphism is associated with renal disease in systemic lupus erythematosus patients. , 1995, Arthritis and rheumatism.

[11]  L. M. Srivastava,et al.  Hind III genomic polymorphism of the C3b receptor (CR1) in patients with SLE: Low erythrocyte CR1 expression is an acquired phenomenon , 1995, Immunology and cell biology.

[12]  C. Berry,et al.  Modulation of disease activity in murine systemic lupus erythematosus by cytokine gene delivery , 1995, Lupus.

[13]  A. Theofilopoulos.  The basis of autoimmunity: Part II. Genetic predisposition. , 1995, Immunology today.

[14]  C. Drake,et al.  Analysis of the New Zealand Black contribution to lupus-like renal disease. Multiple genes that operate in a threshold manner. , 1995, Journal of immunology.

[15]  M. B. Frank,et al.  The location of a disease-associated polymorphism and genomic structure of the human 52-kDa Ro/SSA locus (SSA1). , 1994, Genomics.

[16]  J. Harley,et al.  Systemic lupus erythematosus: considerations for a genetic approach. , 1994, The Journal of investigative dermatology.

[17]  R. Balderas,et al.  Lupus susceptibility loci in New Zealand mice. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[18]  G. Thomson.  Identifying complex disease genes: progress and paradigms , 1994, Nature Genetics.

[19]  M. Walport,et al.  Hereditary C1q deficiency and systemic lupus erythematosus. , 1994, QJM : monthly journal of the Association of Physicians.

[20]  R. Burlingame,et al.  The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus. , 1994, The Journal of clinical investigation.

[21]  B. Tsao,et al.  Comparison of pathogenic and non-pathogenic murine antibodies to DNA: antigen binding and structural characteristics. , 1994, International immunology.

[22]  E. Wakeland,et al.  Polygenic control of susceptibility to murine systemic lupus erythematosus. , 1994, Immunity.

[23]  Lee Js,et al.  Altered poly(ADP-ribose) metabolism in family members of patients with systemic lupus erythematosus. , 1994 .

[24]  C. Drake,et al.  Genetic analysis of the NZB contribution to lupus-like autoimmune disease in (NZB x NZW)F1 mice. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[25]  C. Mohan,et al.  Nucleosome: a major immunogen for pathogenic autoantibody-inducing T cells of lupus , 1993, The Journal of experimental medicine.

[26]  D. Agus,et al.  A human homeobox gene, HB24, inhibits development of CD4+ T cells and impairs thymic involution in transgenic mice. , 1993, The Journal of biological chemistry.

[27]  J. Murray,et al.  Linkage localization of TGFB2 and the human homeobox gene HLX1 to chromosome 1q. , 1993, Genomics.

[28]  M. Seldin,et al.  Genetic analysis of MRL-lpr mice: relationship of the Fas apoptosis gene to disease manifestations and renal disease-modifying loci , 1992, The Journal of experimental medicine.

[29]  M. Teitell,et al.  Failed self-tolerance and autoimmunity in IgG anti-DNA transgenic mice. , 1992, Journal of immunology.

[30]  M. Kazatchkine,et al.  Increased frequency of the long (S) allotype of CR1 (the C3b/C4b receptor, CD35) in patients with systemic lupus erythematosus , 1992, Clinical and Experimental Immunology.

[31]  A Collins,et al.  Algorithms for a location database , 1992, Annals of human genetics.

[32]  J. Hewett,et al.  Association of immunoglobulin Km and Gm allotypes with specific antinuclear antibodies and disease susceptibility among connective tissue disease patients. , 1991, Arthritis and rheumatism.

[33]  R. Burlingame,et al.  Subnucleosome structures as substrates in enzyme-linked immunosorbent assays. , 1990, Journal of immunological methods.

[34]  P. Schur,et al.  Association between a T cell receptor restriction fragment length polymorphism and systemic lupus erythematosus. , 1990, The Journal of clinical investigation.

[35]  M. Hochberg,et al.  Systemic lupus erythematosus. , 1990, Rheumatic diseases clinics of North America.

[36]  D. Bell,et al.  Immunogenic DNA-related factors. Nucleosomes spontaneously released from normal murine lymphoid cells stimulate proliferation and immunoglobulin synthesis of normal mouse lymphocytes. , 1990, The Journal of clinical investigation.

[37]  N. Risch.  Linkage strategies for genetically complex traits. II. The power of affected relative pairs. , 1990, American journal of human genetics.

[38]  H. Mcdevitt,et al.  Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythematosus. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[39]  B. Zabel,et al.  Human nuclear NAD+ ADP-ribosyltransferase: localization of the gene on chromosome 1q41-q42 and expression of an active human enzyme in Escherichia coli. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[40]  B. Haendler,et al.  Complementary DNA for human glioblastoma‐derived T cell suppressor factor, a novel member of the transforming growth factor‐beta gene family. , 1987, The EMBO journal.

[41]  F. Althaus,et al.  Poly(ADP-ribose) may signal changing metabolic conditions to the chromatin of mammalian cells. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[42]  K. Shi,et al.  [The epidemiology of systemic lupus erythematosus in Shanghai]. , 1985, Zhonghua nei ke za zhi.

[43]  P. Schur,et al.  Gm allotypes in white patients with systemic lupus erythematosus. , 1985, Arthritis and rheumatism.

[44]  J. Ott.  Analysis of Human Genetic Linkage , 1985 .

[45]  R. Elston,et al.  The investigation of linkage between a quantitative trait and a marker locus , 1972, Behavior genetics.

[46]  B. Kotzin.  Systemic lupus erythematosus. , 1996, Cell.

[47]  J. Gauthier,et al.  The 8.5-kb PstI allele of the stress protein gene, Hsp70-2: an independent risk factor for systemic lupus erythematosus in African Americans? , 1996, Human immunology.

[48]  J. Klinenberg,et al.  A greater variability in the 3' flanking region of the IL-6 gene in patients with systemic lupus erythematosus (SLE). , 1996, Autoimmunity.

[49]  W. Thomson,et al.  Mannose-binding protein gene polymorphism in systemic lupus erythematosus. , 1995, Arthritis and rheumatism.

[50]  J. Todd,et al.  Linkage disequilibrium mapping of a type 1 diabetes susceptibility gene (IDDM7) to chromosome 2q31–q33 , 1995, Nature Genetics.

[51]  J. S. Lee,et al.  Altered poly(ADP-ribose) metabolism in family members of patients with systemic lupus erythematosus. , 1994, Journal of Rheumatology.

[52]  E. Lander,et al.  Genetic dissection of complex traits science , 1994 .

[53]  R. Cantor.  A linkage test with identity-by-descent marker data from pairs of affected relatives. , 1989, Progress in clinical and biological research.

[54]  Canto Rm.  A linkage test with identity-by-descent marker data from pairs of affected relatives. , 1989 .

[55]  R. Derynck,et al.  Chromosomal mapping of genes for transforming growth factors beta 2 and beta 3 in man and mouse: dispersion of TGF-beta gene family. , 1988, Oncogene research.

[56]  N Risch,et al.  Assessing the role of HLA-linked and unlinked determinants of disease. , 1987, American journal of human genetics.

[57]  R. Elston,et al.  A comparison of sib‐pair linkage tests for disease susceptibility loci , 1985, Genetic epidemiology.

[58]  Blackwelder Wc,et al.  A comparison of sib-pair linkage tests for disease susceptibility loci , 1985 .

[59]  Stanley L. Lee,et al.  The epidemiology of systemic lupus erythematosus. , 1973, Seminars in arthritis and rheumatism.