Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Full Paper
  • Published:

Fine mapping chromosome 16q12 in a collection of 231 systemic lupus erythematosus sibpair and multiplex families

Genes & Immunity volume 6, pages 19–23 (2005)Cite this article

Abstract

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disorder influenced by multiple genetic and environmental factors. Linkage of SLE to chromosome 16q12–13 (LOD score=3.85) was first identified in pedigrees collected at the University of Minnesota, and has been replicated in several independent SLE collections. We performed fine mapping using microsatellites to further refine the susceptibility region(s), and the best evidence for linkage was identified at marker D16S3396 (LOD=2.28, P=0.0006). Evidence of association was suggested in the analysis of all families (D16S3094, P=0.0516) and improved to the level of significance (P=0.0106) when only the Caucasian families were analyzed. Subsets of pedigrees were then selected on the basis of clinical manifestations, and these subsets showed evidence for association with several markers: GATA143D05 (renal, P=0.0064), D16S3035 (renal, P=0.0418), D16S3117 (renal, P=0.0366), D16S3071 (malar rash, P=0.03638; neuropsychiatric, P=0.0349; oral ulcers, P=0.0459), D16S3094 (hematologic, P=0.0226), and D16S3089 (arthritis, P=0.0141). Together, these data provide further evidence that an important susceptibility gene(s) for SLE is located at 16q12.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Hochberg MC . The epidemiology of systemic lupus erythematosus. In: Wallace DJ, Hahn BH (eds). Dubois' Lupus Erythematosus. Williams & Wilkins: Baltimore, 1997, pp 49–65.

    Google Scholar 

  2. Michet Jr CJ, McKenna CH, Elveback LR, Kaslow RA, Kurland LT . Epidemiology of systemic lupus erythematosus and other connective tissue diseases in Rochester, Minnesota 1950 through 1979. Mayo Clin Proc 1985; 60: 105–113.

    Article  Google Scholar 

  3. Lawrence RC, Helmick CG, Arnett FC et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1998; 41: 778–799.

    Article  CAS  Google Scholar 

  4. Hart HH, Grigor RR, Caughey DE . Ethnic difference in the prevalence of systemic lupus erythematosus. Ann Rhuem Dis 1983; 42: 529–532.

    Article  CAS  Google Scholar 

  5. Serdula MK, Rhoads GG . Frequency of systemic lupus erythematosus in different ethnic groups in Hawaii. Arthritis Rheum 1979; 22: 328–333.

    Article  CAS  Google Scholar 

  6. Hochberg MC . The application of genetic epidemiology to systemic lupus erythematosus. J Rheumatol 1987; 14: 867–869.

    CAS  PubMed  Google Scholar 

  7. Vyse TJ, Todd JA . Genetic analysis of autoimmune disease. Cell 1996; 85: 311–318.

    Article  CAS  Google Scholar 

  8. Lawrence JS, Martins CL, Drake GL . A family survey of lupus erythematosus. 1. Heritability. J Rheumatol 1987; 14: 913–921.

    CAS  PubMed  Google Scholar 

  9. Block SR, Winfield JB, Lockshin MD, D'Angelo WA, Christian CL . Studies of twins with systemic lupus erythematosus. A review of the literature and presentation of 12 additional sets. Am J Med 1975; 59: 533–552.

    Article  CAS  Google Scholar 

  10. Deapen D, Escalante A, Weinrib L et al. A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis Rheum 1992; 35: 311–318.

    Article  CAS  Google Scholar 

  11. Mongey AB, Hess EV . The role of the environment in systemic lupus erythematosus and associated disorders. In: Wallace DJ, Hahn BH (eds). Dubois' Lupus Erythematosus. Williams & Wilkins: Baltimore, 1997, pp 33–64.

    Google Scholar 

  12. Lander E, Kruglyak L . Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 1995; 11: 241–247.

    Article  CAS  Google Scholar 

  13. Tsao BP, Cantor RM, Kalunian KC et al. Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus. J Clin Invest 1997; 99: 725–731.

    Article  CAS  Google Scholar 

  14. Moser KL, Neas BR, Salmon JE et al. Genome scan of human systemic lupus erythematosus: evidence for linkage on chromosome 1q in African-American pedigrees. Proc Natl Acad Sci USA 1998; 95: 14869–14874.

    Article  CAS  Google Scholar 

  15. Gaffney PM, Kearns GM, Shark KB et al. A genome-wide search for susceptibility genes in human systemic lupus erythematosus sib-pair families. Proc Natl Acad Sci USA 1998; 95: 14875–14879.

    Article  CAS  Google Scholar 

  16. Shai R, Quismorio Jr FP, Li L et al. Genome-wide screen for systemic lupus erythematosus susceptibility genes in multiplex families. Hum Mol Genet 1999; 8: 639–644.

    Article  CAS  Google Scholar 

  17. Moser KL, Gray-McGuire C, Kelly J et al. Confirmation of genetic linkage between human systemic lupus erythematosus and chromosome 1q41. Arthritis Rheum 1999; 42: 1902–1907.

    Article  CAS  Google Scholar 

  18. Gaffney PM, Ortmann WA, Selby SA 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: 547–556.

    Article  CAS  Google Scholar 

  19. Lindqvist AK, Steinsson K, Johanneson B et al. A susceptibility locus for human systemic lupus erythematosus (hSLE1) on chromosome 2q. J Autoimmun 2000; 14: 169–178.

    Article  CAS  Google Scholar 

  20. Gray-McGuire C, Moser KL, Gaffney PM et al. Genome scan of human systemic lupus erythematosus by regression modeling: evidence of linkage and epistasis at 4p16–15.2. Am J Hum Genet 2000; 67: 1460–1469.

    Article  CAS  Google Scholar 

  21. Johanneson B, Lima G, von Salome J, Alarcon-Segovia D, Alarcon-Riquelme ME . A major susceptibility locus for systemic lupus erythematosus maps to chromosome 1q31. Am J Hum Genet 2002; 71: 1060–1071.

    Article  CAS  Google Scholar 

  22. Tsao BP, Cantor RM, Grossman JM et al. Linkage and interaction of loci on 1q23 and 16q12 may contribute to susceptibility to systemic lupus erythematosus. Arthritis Rheum 2002; 46: 2928–2936.

    Article  CAS  Google Scholar 

  23. Nath SK, Kelly JA, Namjou B et al. Evidence for a susceptibility gene, SLEV1, on chromosome 17p13 in families with vitiligo-related systemic lupus erythematosus. Am J Hum Genet 2001; 69: 1401–1406.

    Article  CAS  Google Scholar 

  24. Nath SK, Namjou B, Hutchings D et al. Systemic lupus erythematosus (SLE) and chromosome 16: confirmation of linkage to 16q12–13 and evidence for genetic heterogeneity. Eur J Hum Genet 2004; 12: 1–5.

    Article  Google Scholar 

  25. Feng XB, Shen N, Chen SL et al. Susceptibility gene of systemic lupus erythematosus in 16q12 in Chinese cohort. Chinese J Med Genet 2003; 20: 27–30.

    CAS  Google Scholar 

  26. Abecasis GR, Cherny SS, Cookson WO, Cardon LR . Merlin-rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 2002; 30: 97–101.

    Article  CAS  Google Scholar 

  27. Nath SK, Quintero-Del-Rio AI, Kilpatrick J, Feo L, Ballesteros M, Harley JB . Linkage at 12q24 with systemic lupus erythematosus (SLE) is established and confirmed in Hispanic and European American families. Am J Hum Genet 2004; 74: 73–82.

    Article  CAS  Google Scholar 

  28. Hochberg MC . Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725.

    Article  CAS  Google Scholar 

  29. Tan EM, Cohen AS, Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–1277.

    Article  CAS  Google Scholar 

  30. Ogura Y, Bonen D, Inohara N et al. A frame shift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 2001; 411: 603–606.

    Article  CAS  Google Scholar 

  31. Karason A, Gudjonsson JE, Upmanyu R et al. A susceptibility gene for psoriatic arthritis maps to chromosome 16q: evidence for imprinting. Am J Hum Genet 2003; 72: 125–131.

    Article  CAS  Google Scholar 

  32. Rahman P, Bartlett S, Siannis F et al. Pleiotropic CARD15: a pleiotropic autoimmune gene that confers susceptibility to psoriatic arthritis. Am J Hum Genet 2003; 73: 677–681.

    Article  CAS  Google Scholar 

  33. Orgura Y, Inohara N, Benito A, Chen FF, Yamaoka S, Nunez G . Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-κB. J Biol Chem 2001; 276: 4812–4818.

    Article  Google Scholar 

  34. Gergely Jr P, Grossman C, Niland B et al. Mitochondrial hyperpolarization and ATP depletion in patients with systemic lupus erythematosus. Arthritis Rheum 2002; 46: 175–190.

    Article  CAS  Google Scholar 

  35. Casciola-Rosen LA, Anhalt G, Rosen A . Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med 1994; 179: 1317–1330.

    Article  CAS  Google Scholar 

  36. Utz PJ, Hottelet M, Schur PM, Anderson P . Proteins phosphorylated during stress-induced apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus. J Exp Med 1997; 185: 843–854.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to the patients and their families for their participation. This work was supported by grants from the National Institutes of Health RO1 AR043274 (to TWB), a JV Satterfield Arthritis Investigator Award from the National Arthritis Foundation (KLM), and the Lupus Foundation of Minnesota (KLM).

Author information

Authors and Affiliations

  1. Department of Molecular, Cellular, Developmental Biology and Genetics, University of Minnesota, Minneapolis, MN, USA

    C D Gillett, P M Gaffney, T W Behrens & K L Moser

  2. Department of Medicine and the Center for Lupus Research, University of Minnesota, Minneapolis, MN, USA

    C D Gillett, W A Ortmann, P R Rodine, S A Selby, P M Gaffney, T W Behrens & K L Moser

  3. Department of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, NC, USA

    C D Langefeld & A H Williams

  4. Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    R R Graham

Authors
  1. C D Gillett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C D Langefeld
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A H Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W A Ortmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R R Graham
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P R Rodine
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S A Selby
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P M Gaffney
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. T W Behrens
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. K L Moser
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K L Moser.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gillett, C., Langefeld, C., Williams, A. et al. Fine mapping chromosome 16q12 in a collection of 231 systemic lupus erythematosus sibpair and multiplex families. Genes Immun 6, 19–23 (2005). https://doi.org/10.1038/sj.gene.6364145

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6364145

Keywords

This article is cited by

Search

Advanced search

Quick links