The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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Clinical implications of copy number variations in autoimmune disorders

  • Yim, Seon-Hee (Department of Medical Education, College of Medicine, The Catholic University of Korea) ;
  • Jung, Seung-Hyun (Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea) ;
  • Chung, Boram (Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea) ;
  • Chung, Yeun-Jun (Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea)
  • Received : 2015.03.25
  • Accepted : 2015.03.30
  • Published : 2015.05.01
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Abstract

Human genetic variation is represented by the genetic differences both within and among populations, and most genetic variants do not cause overt diseases but contribute to disease susceptibility and influence drug response. During the last century, various genetic variants, such as copy number variations (CNVs), have been associated with diverse human disorders. Here, we review studies on the associations between CNVs and autoimmune diseases to gain some insight. First, some CNV loci are commonly implicated in various autoimmune diseases, such as $Fc{\gamma}$ receptors in patients with systemic lupus erythemoatosus or idiopathic thrombocytopenic purpura and ${\beta}-defensin$ genes in patients with psoriasis or Crohn's disease. This means that when a CNV locus is associated with a particular autoimmune disease, we should examine its potential associations with other diseases. Second, interpopulation or interethnic differences in the effects of CNVs on phenotypes exist, including disease susceptibility, and evidence suggests that CNVs are important to understand susceptibility to and pathogenesis of autoimmune diseases. However, many findings need to be replicated in independent populations and different ethnic groups. The validity and reliability of detecting CNVs will improve quickly as genotyping technology advances, which will support the required replication.

Keywords

Acknowledgement

Supported by : Ministry for Health and Welfare

References

  1. Goodnow CC. Multistep pathogenesis of autoimmune disease. Cell 2007;130:25-35. https://doi.org/10.1016/j.cell.2007.06.033
  2. Ohno S, Wolf U, Atkin NB. Evolution from fish to mammals by gene duplication. Hereditas 1968;59:169-187.
  3. Rioux JD, Abbas AK. Paths to understanding the genetic basis of autoimmune disease. Nature 2005;435:584-589. https://doi.org/10.1038/nature03723
  4. Astorga GP, Williams RC Jr. Altered reactivity in mixed lymphocyte culture of lymphocytes from patients with rheumatoid arthritis. Arthritis Rheum 1969;12:547-554. https://doi.org/10.1002/art.1780120602
  5. Robinson PC, Brown MA. Genetics of ankylosing spondylitis. Mol Immunol 2014;57:2-11. https://doi.org/10.1016/j.molimm.2013.06.013
  6. International HapMap Consortium. A haplotype map of the human genome. Nature 2005;437:1299-1320. https://doi.org/10.1038/nature04226
  7. McCarroll SA, Altshuler DM. Copy-number variation and association studies of human disease. Nat Genet 2007;39(7 Suppl):S37-S42. https://doi.org/10.1038/ng2080
  8. Yim SH, Kim TM, Hu HJ, et al. Copy number variations in East-Asian population and their evolutionary and functional implications. Hum Mol Genet 2010;19:1001-1008. https://doi.org/10.1093/hmg/ddp564
  9. Hirschhorn JN, Daly MJ. Genome-wide association studies for common diseases and complex traits. Nat Rev Genet 2005;6:95-108.
  10. Wellcome Trust Case Control Consortium, Craddock N, Hurles ME, et al. Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature 2010;464:713-720. https://doi.org/10.1038/nature08979
  11. Stahl EA, Raychaudhuri S, Remmers EF, et al. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet 2010;42:508-514. https://doi.org/10.1038/ng.582
  12. Graham RR, Cotsapas C, Davies L, et al. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet 2008;40:1059-1061. https://doi.org/10.1038/ng.200
  13. Jung SH, Yim SH, Hu HJ, et al. Genome-wide copy number variation analysis identifies deletion variants associated with ankylosing spondylitis. Arthritis Rheumatol 2014;66:2103-2112. https://doi.org/10.1002/art.38650
  14. Kim JH, Jung SH, Bae JS, et al. Deletion variants of RABGAP1L, 10q21.3, and C4 are associated with the risk of systemic lupus erythematosus in Korean women. Arthritis Rheum 2013;65:1055-1063. https://doi.org/10.1002/art.37854
  15. Okada Y, Wu D, Trynka G, et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 2014;506:376-381. https://doi.org/10.1038/nature12873
  16. McCarroll SA, Hadnott TN, Perry GH, et al. Common deletion polymorphisms in the human genome. Nat Genet 2006;38:86-92. https://doi.org/10.1038/ng1696
  17. Iafrate AJ, Feuk L, Rivera MN, et al. Detection of largescale variation in the human genome. Nat Genet 2004;36:949-951. https://doi.org/10.1038/ng1416
  18. Sebat J, Lakshmi B, Troge J, et al. Large-scale copy number polymorphism in the human genome. Science 2004;305:525-528. https://doi.org/10.1126/science.1098918
  19. Feuk L, Carson AR, Scherer SW. Structural variation in the human genome. Nat Rev Genet 2006;7:85-97.
  20. Human Genome Structural Variation Working Group, Eichler EE, Nickerson DA, et al. Completing the map of human genetic variation. Nature 2007;447:161-165. https://doi.org/10.1038/447161a
  21. The Centre for Applied Genomics. Database of genomic variants [Internet]. Toronto (ON): The Centre for Applied Genomics, 2014 [cited 2015 Feb 2]. Available from: http://dgv.tcag.ca/dgv/app/statistics?ref=.
  22. Kidd JM, Cooper GM, Donahue WF, et al. Mapping and sequencing of structural variation from eight human genomes. Nature 2008;453:56-64. https://doi.org/10.1038/nature06862
  23. Chen L, Zhou W, Zhang L, Zhang F. Genome architecture and its roles in human copy number variation. Genomics Inform 2014;12:136-144. https://doi.org/10.5808/GI.2014.12.4.136
  24. van Ommen GJ. Frequency of new copy number variation in humans. Nat Genet 2005;37:333-334. https://doi.org/10.1038/ng0405-333
  25. Aten E, White SJ, Kalf ME, et al. Methods to detect CNVs in the human genome. Cytogenet Genome Res 2008;123:313-321. https://doi.org/10.1159/000184723
  26. Kim TM, Yim SH, Chung YJ. Copy number variations in the human genome: potential source for individual diversity and disease association studies. Genomics Inform 2008;6:1-7. https://doi.org/10.5808/GI.2008.6.1.001
  27. Lin CF, Naj AC, Wang LS. Analyzing copy number variation using SNP array data: protocols for calling CNV and association tests. Curr Protoc Hum Genet 2013;79:Unit 1.27.
  28. Wang J, Wang W, Li R, et al. The diploid genome sequence of an Asian individual. Nature 2008;456:60-65. https://doi.org/10.1038/nature07484
  29. Kim JI, Ju YS, Park H, et al. A highly annotated whole-genome sequence of a Korean individual. Nature 2009; 460:1011-1015. https://doi.org/10.1038/nature08211
  30. Abel HJ, Duncavage EJ. Detection of structural DNA variation from next generation sequencing data: a review of informatic approaches. Cancer Genet 2013;206:432-440. https://doi.org/10.1016/j.cancergen.2013.11.002
  31. Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G. Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 2002;30:e57. https://doi.org/10.1093/nar/gnf056
  32. Shin GW, Jung SH, Yim SH, Chung B, Yeol Jung G, Chung YJ. Stuffer-free multiplex ligation-dependent probe amplification based on conformation-sensitive capillary electrophoresis: a novel technology for robust multiplex determination of copy number variation. Electrophoresis 2012;33:3052-3061. https://doi.org/10.1002/elps.201200334
  33. Zerrahn J, Held W, Raulet DH. The MHC reactivity of the T cell repertoire prior to positive and negative selection. Cell 1997;88:627-636. https://doi.org/10.1016/S0092-8674(00)81905-4
  34. Cho JH, Gregersen PK. Genomics and the multifactorial nature of human autoimmune disease. N Engl J Med 2011;365:1612-1623. https://doi.org/10.1056/NEJMra1100030
  35. Chung EK, Yang Y, Rupert KL, et al. Determining the one, two, three, or four long and short loci of human complement C4 in a major histocompatibility complex haplotype encoding C4A or C4B proteins. Am J Hum Genet 2002;71:810-822. https://doi.org/10.1086/342778
  36. Yang Y, Chung EK, Wu YL, et al. Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European Americans. Am J Hum Genet 2007;80:1037-1054. https://doi.org/10.1086/518257
  37. Lv Y, He S, Zhang Z, et al. Confirmation of C4 gene copy number variation and the association with systemic lupus erythematosus in Chinese Han population. Rheumatol Int 2012;32:3047-3053. https://doi.org/10.1007/s00296-011-2023-7
  38. Boteva L, Morris DL, Cortes-Hernandez J, Martin J, Vyse TJ, Fernando MM. Genetically determined partial complement C4 deficiency states are not independent risk factors for SLE in UK and Spanish populations. Am J Hum Genet 2012;90:445-456. https://doi.org/10.1016/j.ajhg.2012.01.012
  39. Rigby WF, Wu YL, Zan M, et al. Increased frequency of complement C4B deficiency in rheumatoid arthritis. Arthritis Rheum 2012;64:1338-1344. https://doi.org/10.1002/art.33472
  40. Nimmerjahn F, Ravetch JV. Fc-receptors as regulators of immunity. Adv Immunol 2007;96:179-204. https://doi.org/10.1016/S0065-2776(07)96005-8
  41. Kocher M, Siegel ME, Edberg JC, Kimberly RP. Cross-linking of Fc gamma receptor IIa and Fc gamma receptor IIIb induces different proadhesive phenotypes on human neutrophils. J Immunol 1997;159:3940-3948.
  42. Aitman TJ, Dong R, Vyse TJ, et al. Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature 2006;439:851-855. https://doi.org/10.1038/nature04489
  43. Fanciulli M, Norsworthy PJ, Petretto E, et al. FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity. Nat Genet 2007;39:721-723. https://doi.org/10.1038/ng2046
  44. Mamtani M, Anaya JM, He W, Ahuja SK. Association of copy number variation in the FCGR3B gene with risk of autoimmune diseases. Genes Immun 2010;11:155-160. https://doi.org/10.1038/gene.2009.71
  45. Morris DL, Roberts AL, Witherden AS, et al. Evidence for both copy number and allelic (NA1/NA2) risk at the FCGR3B locus in systemic lupus erythematosus. Eur J Hum Genet 2010;18:1027-1031. https://doi.org/10.1038/ejhg.2010.56
  46. McKinney C, Fanciulli M, Merriman ME, et al. Association of variation in Fcgamma receptor 3B gene copy number with rheumatoid arthritis in Caucasian samples. Ann Rheum Dis 2010;69:1711-1716. https://doi.org/10.1136/ard.2009.123588
  47. Robinson JI, Carr IM, Cooper DL, et al. Confirmation of association of FCGR3B but not FCGR3A copy number with susceptibility to autoantibody positive rheumatoid arthritis. Hum Mutat 2012;33:741-749. https://doi.org/10.1002/humu.22031
  48. McKinney C, Merriman TR. Meta-analysis confirms a role for deletion in FCGR3B in autoimmune phenotypes. Hum Mol Genet 2012;21:2370-2376. https://doi.org/10.1093/hmg/dds039
  49. McKinney C, Merriman ME, Chapman PT, et al. Evidence for an inf luence of chemokine ligand 3-like 1 (CCL3L1) gene copy number on susceptibility to rheumatoid arthritis. Ann Rheum Dis 2008;67:409-413.
  50. Gonzalez E, Kulkarni H, Bolivar H, et al. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 2005;307:1434-1440. https://doi.org/10.1126/science.1101160
  51. Mamtani M, Rovin B, Brey R, et al. CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus. Ann Rheum Dis 2008;67:1076-1083. https://doi.org/10.1136/ard.2007.078048
  52. Burns JC, Shimizu C, Gonzalez E, et al. Genetic variations in the receptor-ligand pair CCR5 and CCL3L1 are important determinants of susceptibility to Kawasaki disease. J Infect Dis 2005;192:344-349. https://doi.org/10.1086/430953
  53. Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 2003;3:710-720. https://doi.org/10.1038/nri1180
  54. Yang D, Chertov O, Bykovskaia SN, et al. Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 1999;286:525-528. https://doi.org/10.1126/science.286.5439.525
  55. Niyonsaba F, Ogawa H, Nagaoka I. Human beta-defensin-2 functions as a chemotactic agent for tumour necrosis factor-alpha-treated human neutrophils. Immunology 2004;111:273-281. https://doi.org/10.1111/j.0019-2805.2004.01816.x
  56. Hollox EJ, Huffmeier U, Zeeuwen PL, et al. Psoriasis is associated with increased beta-defensin genomic copy number. Nat Genet 2008;40:23-25. https://doi.org/10.1038/ng.2007.48
  57. Wehkamp J, Harder J, Weichenthal M, et al. Inducible and constitutive beta-defensins are differentially expressed in Crohn's disease and ulcerative colitis. Inflamm Bowel Dis 2003;9:215-223. https://doi.org/10.1097/00054725-200307000-00001
  58. Fellermann K, Stange DE, Schaeffeler E, et al. A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am J Hum Genet 2006;79:439-448. https://doi.org/10.1086/505915
  59. Bentley RW, Pearson J, Gearry RB, et al. Association of higher DEFB4 genomic copy number with Crohn's disease. Am J Gastroenterol 2010;105:354-359. https://doi.org/10.1038/ajg.2009.582
  60. Aldhous MC, Abu Bakar S, Prescott NJ, et al. Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn's disease. Hum Mol Genet 2010;19:4930-4938. https://doi.org/10.1093/hmg/ddq411
  61. Zhou XJ, Cheng FJ, Lv JC, et al. Higher DEFB4 genomic copy number in SLE and ANCA-associated small vasculitis. Rheumatology (Oxford) 2012;51:992-995. https://doi.org/10.1093/rheumatology/ker419
  62. Singh SB, Davis AS, Taylor GA, Deretic V. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 2006;313:1438-1441. https://doi.org/10.1126/science.1129577
  63. Parkes M, Barrett JC, Prescott NJ, et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat Genet 2007;39:830-832. https://doi.org/10.1038/ng2061
  64. McCarroll SA, Huett A, Kuballa P, et al. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease. Nat Genet 2008;40:1107-1112. https://doi.org/10.1038/ng.215
  65. Brest P, Lapaquette P, Souidi M, et al. A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn's disease. Nat Genet 2011;43:242-245. https://doi.org/10.1038/ng.762
  66. Prescott NJ, Dominy KM, Kubo M, et al. Independent and population-specific association of risk variants at the IRGM locus with Crohn's disease. Hum Mol Genet 2010;19:1828-1839. https://doi.org/10.1093/hmg/ddq041
  67. Viau M, Zouali M. B-lymphocytes, innate immunity, and autoimmunity. Clin Immunol 2005;114:17-26. https://doi.org/10.1016/j.clim.2004.08.019
  68. Zouali M. Transcriptional and metabolic pre-B cell receptor-mediated checkpoints: implications for autoimmune diseases. Mol Immunol 2014;62:315-320. https://doi.org/10.1016/j.molimm.2014.01.009
  69. Yim SH, Chung YJ, Jin EH, et al. The potential role of VPREB1 gene copy number variation in susceptibility to rheumatoid arthritis. Mol Immunol 2011;48:1338-1343. https://doi.org/10.1016/j.molimm.2010.11.009

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