Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs
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- 作者：Steven G. Friedenberg ; Greg Buhrman ; Lhoucine Chdid ; Natasha J. Olby…
- 关键词：Canine ; Immune ; mediated disease ; Dog leukocyte antigen ; Major histocompatibility complex class Ib
- 刊名：Immunogenetics
- 出版年：2016
- 出版时间：March 2016
- 年：2016
- 卷：68
- 期：3
- 页码：205-217
- 全文大小：2,029 KB
- 参考文献：Adams PD, Afonine PV, Bunkóczi G et al (2010) PHENIX: a comprehensive python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66:213–221. doi:10.1107/S0907444909052925 PubMedCentral CrossRef PubMed
Allen RL, Hogan L (2013) Non- classical MHC class I molecules (MHC-Ib). In: eLS. Wiley, Chichester. http://www.els.net . doi:10.1002/9780470015902.a0024246
Arnold K, Bordoli L, Kopp J, Schwede T (2006) The SWISS-MODEL workspace: a Web-based environment for protein structure homology modelling. Bioinformatics 22:195–201. doi:10.1093/bioinformatics/bti770 CrossRef PubMed
Barber RM, Schatzberg SJ, Corneveaux JJ et al (2011) Identification of risk loci for necrotizing meningoencephalitis in Pug dogs. J Hered 102(Suppl 1):S40–S46. doi:10.1093/jhered/esr048 CrossRef PubMed
Bayer AL, Pugliese A, Malek TR (2013) The IL-2/IL-2R system: from basic science to therapeutic applications to enhance immune regulation. Immunol Res 57:197–209. doi:10.1007/s12026-013-8452-5 PubMedCentral CrossRef PubMed
Benkert P, Biasini M, Schwede T (2011) Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics 27:343–350. doi:10.1093/bioinformatics/btq662 PubMedCentral CrossRef PubMed
Biasini M, Bienert S, Waterhouse A et al (2014) SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res 42:W252–W258. doi:10.1093/nar/gku340 PubMedCentral CrossRef PubMed
Bogdanos DP, Smyk DS, Rigopoulou EI et al (2012) Twin studies in autoimmune disease: genetics, gender and environment. J Autoimmun 38:J156–J169. doi:10.1016/j.jaut.2011.11.003 CrossRef PubMed
Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30:2114–2120. doi:10.1093/bioinformatics/btu170 PubMedCentral CrossRef PubMed
Brenke R, Kozakov D, Chuang G-Y et al (2009) Fragment-based identification of druggable “hot spots” of proteins using Fourier domain correlation techniques. Bioinformatics 25:621–627. doi:10.1093/bioinformatics/btp036 PubMedCentral CrossRef PubMed
Buhrman G, O’Connor C, Zerbe B et al (2011) Analysis of binding site hot spots on the surface of Ras GTPase. J Mol Biol 413:773–789. doi:10.1016/j.jmb.2011.09.011 PubMedCentral CrossRef PubMed
Burnett RC, Geraghty DE (1995) Structure and expression of a divergent canine class I gene. J Immunol 155:4278–4285PubMed
Callan MB, Werner P, Mason NJ et al (2013) Polymorphisms in canine platelet glycoproteins identify potential platelet antigens. Comp Med 63:348–354PubMedCentral PubMed
Carr AP, Panciera DL, Kidd L (2002) Prognostic factors for mortality and thromboembolism in canine immune-mediated hemolytic anemia: a retrospective study of 72 dogs. J Vet Intern Med 16:504–509CrossRef PubMed
Castiblanco J, Arcos-Burgos M, Anaya J-M (2013) What is next after the genes for autoimmunity? BMC Med 11:197–206. doi:10.1186/1741-7015-11-197 PubMedCentral CrossRef PubMed
Catchpole B, Adams JP, Holder AL et al (2013) Genetics of canine diabetes mellitus: are the diabetes susceptibility genes identified in humans involved in breed susceptibility to diabetes mellitus in dogs? Vet J 195:139–147. doi:10.1016/j.tvjl.2012.11.013 CrossRef PubMed
Chase K, Sargan D, Miller K et al (2006) Understanding the genetics of autoimmune disease: two loci that regulate late onset Addison’s disease in Portuguese water dogs. Int J Immunogenet 33:179–184. doi:10.1111/j.1744-313X.2006.00593.x PubMedCentral CrossRef PubMed
Cho JH, Gregersen PK (2011) Genomics and the multifactorial nature of human autoimmune disease. N Engl J Med 365:1612–1623. doi:10.1056/NEJMra1100030 CrossRef PubMed
Cingolani P, Platts A, Wang LL et al (2012) A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly (Austin) 6:80–92. doi:10.4161/fly.19695 CrossRef
Clements DN, Gear RNA, Tattersall J et al (2004) Type I immune-mediated polyarthritis in dogs: 39 cases (1997–2002). J Am Vet Med Assoc 224:1323–1327CrossRef PubMed
Corato A, Shen CR, Mazza G et al (1997) Proliferative responses of peripheral blood mononuclear cells from normal dogs and dogs with autoimmune haemolytic anaemia to red blood cell antigens. Vet Immunol Immunopathol 59:191–204CrossRef PubMed
Costenbader KH, Gay S, Alarcón-Riquelme ME et al (2012) Autoimmunity reviews. Autoimmun Rev 11:604–609. doi:10.1016/j.autrev.2011.10.022 CrossRef PubMed
Cotsapas C, Hafler DA (2013) Immune-mediated disease genetics: the shared basis of pathogenesis. Trends Immunol 34:22–26. doi:10.1016/j.it.2012.09.001 CrossRef PubMed
Cotsapas C, Voight BF, Rossin E et al (2011) Pervasive sharing of genetic effects in autoimmune disease. PLoS Genet 7, e1002254. doi:10.1371/journal.pgen.1002254 PubMedCentral CrossRef PubMed
Day MJ (1999) Antigen specificity in canine autoimmune haemolytic anaemia. Vet Immunol Immunopathol 69:215–224CrossRef PubMed
de Almeida DE, Holoshitz J (2011) MHC molecules in health and disease: at the cusp of a paradigm shift. Self Nonself 2:43–48. doi:10.4161/self.2.1.15757 PubMedCentral CrossRef PubMed
DePristo MA, Banks E, Poplin R et al (2011) A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet 43:491–498. doi:10.1038/ng.806 PubMedCentral CrossRef PubMed
Eames HL, Corbin AL, Udalova IA (2015) Interferon regulatory factor 5 in human autoimmunity and murine models of autoimmune disease. Transl Res. doi:10.1016/j.trsl.2015.06.018 PubMed
Emsley P, Lohkamp B, Scott WG, Cowtan K (2010) Features and development of Coot. Acta Crystallogr D Biol Crystallogr 66:486–501. doi:10.1107/S0907444910007493 PubMedCentral CrossRef PubMed
Ettinger R, Kuchen S, Lipsky PE (2008) Interleukin 21 as a target of intervention in autoimmune disease. Ann Rheum Dis 67(Suppl 3):iii83–iii86. doi:10.1136/ard.2008.098400 CrossRef PubMed
Famula TR, Belanger JM, Oberbauer AM (2003) Heritability and complex segregation analysis of hypoadrenocorticism in the standard poodle. J Small Anim Pract 44:8–12CrossRef PubMed
Gee K, Guzzo C, Che Mat NF et al (2009) The IL-12 family of cytokines in infection, inflammation and autoimmune disorders. Inflamm Allergy Drug Targets 8:40–52CrossRef PubMed
Ghoreschi K, Laurence A, O’Shea JJ (2009) Janus kinases in immune cell signaling. Immunol Rev 228:273–287. doi:10.1111/j.1600-065X.2008.00754.x PubMedCentral CrossRef PubMed
Graumann MB, DeRose SA, Ostrander EA, Storb R (1998) Polymorphism analysis of four canine MHC class I genes. Tissue Antigens 51:374–381CrossRef PubMed
Greer KA, Wong AK, Liu H et al (2010) Necrotizing meningoencephalitis of Pug dogs associates with dog leukocyte antigen class II and resembles acute variant forms of multiple sclerosis. Tissue Antigens 76:110–118. doi:10.1111/j.1399-0039.2010.01484.x PubMed
Gregersen PK, Diamond B, Plenge RM (2012) GWAS implicates a role for quantitative immune traits and threshold effects in risk for human autoimmune disorders. Curr Opin Immunol 24:538–543. doi:10.1016/j.coi.2012.09.003 CrossRef PubMed
Guex N, Peitsch MC, Schwede T (2009) Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: a historical perspective. Electrophoresis 30(Suppl 1):S162–S173. doi:10.1002/elps.200900140 CrossRef PubMed
Hoof I, Peters B, Sidney J et al (2009) NetMHCpan, a method for MHC class I binding prediction beyond humans. Immunogenetics 61:1–13. doi:10.1007/s00251-008-0341-z PubMedCentral CrossRef PubMed
Huang AA, Moore GE, Scott-Moncrieff JC (2012) Idiopathic immune-mediated thrombocytopenia and recent vaccination in dogs. J Vet Intern Med 26:142–148. doi:10.1111/j.1939-1676.2011.00850.x CrossRef PubMed
Iyer SS, Cheng G (2012) Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol 32:23–63PubMedCentral CrossRef PubMed
Jiang H, Ware R, Stall A et al (1995) Murine CD8+ T cells that specifically delete autologous CD4+ T cells expressing V beta 8 TCR: a role of the Qa-1 molecule. Immunity 2:185–194CrossRef PubMed
Jiang H, Wu Y, Liang B et al (2005) An affinity/avidity model of peripheral T cell regulation. J Clin Invest 115:302–312. doi:10.1172/JCI23879 PubMedCentral CrossRef PubMed
Johnson KC, Mackin A (2012) Canine immune-mediated polyarthritis: part 1: pathophysiology. J Am Anim Hosp Assoc 48:12–17. doi:10.5326/JAAHA-MS-5744 CrossRef PubMed
Kennedy LJ, Barnes A, Ollier WER, Day MJ (2006a) Association of a common dog leucocyte antigen class II haplotype with canine primary immune-mediated haemolytic anaemia. Tissue Antigens 68:502–508. doi:10.1111/j.1399-0039.2006.00715.x CrossRef PubMed
Kennedy LJ, Quarmby S, Happ GM et al (2006b) Association of canine hypothyroidism with a common major histocompatibility complex DLA class II allele. Tissue Antigens 68:82–86. doi:10.1111/j.1399-0039.2006.00614.x CrossRef PubMed
Kiefer F, Arnold K, Künzli M et al (2009) The SWISS-MODEL Repository and associated resources. Nucleic Acids Res 37:D387–D392. doi:10.1093/nar/gkn750 PubMedCentral CrossRef PubMed
Kim H-J, Wang X, Radfar S et al (2011) CD8+ T regulatory cells express the Ly49 class I MHC receptor and are defective in autoimmune prone B6-Yaa mice. Proc Natl Acad Sci 108:2010–2015. doi:10.1073/pnas.1018974108 PubMedCentral CrossRef PubMed
Korman BD, Kastner DL, Gregersen PK, Remmers EF (2008) STAT4: genetics, mechanisms, and implications for autoimmunity. Curr Allergy Asthma Rep 8:398–403PubMedCentral CrossRef PubMed
Kozakov D, Hall DR, Chuang G-Y et al (2011) Structural conservation of druggable hot spots in protein-protein interfaces. Proc Natl Acad Sci 108:13528–13533. doi:10.1073/pnas.1101835108 PubMedCentral CrossRef PubMed
Lee B, Richards FM (1971) The interpretation of protein structures: estimation of static accessibility. J Mol Biol 55:379–400CrossRef PubMed
Lewis DC, Meyers KM (1996) Canine idiopathic thrombocytopenic purpura. J Vet Intern Med 10:207–218CrossRef PubMed
Li L, Bouvier M (2004) Structures of HLA-A*1101 complexed with immunodominant nonamer and decamer HIV-1 epitopes clearly reveal the presence of a middle, secondary anchor residue. J Immunol 172:6175–6184. doi:10.4049/jimmunol.172.10.6175 CrossRef PubMed
Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25:1754–1760. doi:10.1093/bioinformatics/btp324 PubMedCentral CrossRef PubMed
London N, London N, Raveh B et al (2011) Rosetta FlexPepDock web server—high resolution modeling of peptide-protein interactions. Nucleic Acids Res 39:W249–W253. doi:10.1093/nar/gkr431 PubMedCentral CrossRef PubMed
Massey J, Boag A, Short AD et al (2013a) MHC class II association study in eight breeds of dog with hypoadrenocorticism. Immunogenetics 65:291–297. doi:10.1007/s00251-013-0680-2 CrossRef PubMed
Massey J, Rothwell S, Rusbridge C et al (2013b) Association of an MHC class II haplotype with increased risk of polymyositis in Hungarian Vizsla dogs. PLoS One 8, e56490. doi:10.1371/journal.pone.0056490 PubMedCentral CrossRef PubMed
Massey J, Short AD, Catchpole B et al (2014) Genetics of canine anal furunculosis in the German Shepherd dog. Immunogenetics 66:311–324. doi:10.1007/s00251-014-0766-5 CrossRef PubMed
McCullough S (2003) Immune-mediated hemolytic anemia: understanding the nemesis. Vet Clin North Am Small Anim Pract 33:1295–1315. doi:10.1016/S0195-5616(03)00123-2 CrossRef PubMed
McKenna A, Hanna M, Banks E et al (2010) The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20:1297–1303. doi:10.1101/gr.107524.110 PubMedCentral CrossRef PubMed
McLaren W, Pritchard B, Rios D et al (2010) Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor. Bioinformatics 26:2069–2070. doi:10.1093/bioinformatics/btq330 PubMedCentral CrossRef PubMed
McPhee CG, Sproule TJ, Shin D-M et al (2011) MHC class I family proteins retard systemic lupus erythematosus autoimmunity and B cell lymphomagenesis. J Immunol 187:4695–4704. doi:10.4049/jimmunol.1101776 PubMedCentral CrossRef PubMed
Nielsen M, Lundegaard C, Blicher T et al (2007) NetMHCpan, a method for quantitative predictions of peptide binding to any HLA-A and -B locus protein of known sequence. PLoS One 2, e796. doi:10.1371/journal.pone.0000796 PubMedCentral CrossRef PubMed
Nuttall T, Uri M, Halliwell R (2013) Canine atopic dermatitis—what have we learned? Vet Rec 172:201–207. doi:10.1136/vr.f1134 CrossRef PubMed
Olivry T, DeBoer DJ, Favrot C et al (2010) Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis. Vet Dermatol 21:233–248. doi:10.1111/j.1365-3164.2010.00889.x CrossRef PubMed
O’Marra SK, Delaforcade AM, Shaw SP (2011) Treatment and predictors of outcome in dogs with immune-mediated thrombocytopenia. J Am Vet Med Assoc 238:346–352. doi:10.2460/javma.238.3.346 CrossRef PubMed
Parkes M, Cortes A, van Heel DA, Brown MA (2013) Genetic insights into common pathways and complex relationships among immune-mediated diseases. Nat Rev Genet 14:661–673. doi:10.1038/nrg3502 CrossRef PubMed
Pedersen NC, Liu H, Greenfield DL, Echols LG (2012a) Multiple autoimmune diseases syndrome in Italian Greyhounds: preliminary studies of genome-wide diversity and possible associations within the dog leukocyte antigen (DLA) complex. Vet Immunol Immunopathol 145:264–276. doi:10.1016/j.vetimm.2011.11.015 CrossRef PubMed
Pedersen NC, Liu H, McLaughlin B, Sacks BN (2012b) Genetic characterization of healthy and sebaceous adenitis affected standard poodles from the United States and the United Kingdom. Tissue Antigens 80:46–57. doi:10.1111/j.1399-0039.2012.01876.x CrossRef PubMed
Piek CJ (2011) Canine idiopathic immune-mediated haemolytic anaemia: a review with recommendations for future research. Vet Q 31:129–141. doi:10.1080/01652176.2011.604979 CrossRef PubMed
Raveh B, London N, Schueler-Furman O (2010) Sub-angstrom modeling of complexes between flexible peptides and globular proteins. Proteins 78:2029–2040. doi:10.1002/prot.22716 PubMed
Rawlings DJ, Dai X, Buckner JH (2015) The role of PTPN22 risk variant in the development of autoimmunity: finding common ground between mouse and human. J Immunol 194:2977–2984. doi:10.4049/jimmunol.1403034 CrossRef PubMed
Reich NC (2013) STATs get their move on. JAKSTAT 2:e27080. doi:10.4161/jkst.27080 PubMedCentral PubMed
Rodgers JR, Cook RG (2005) MHC class Ib molecules bridge innate and acquired immunity. Nat Rev Immunol 5:459–471. doi:10.1038/nri1635 CrossRef PubMed
Romo-Tena J, Gómez-Martín D, Alcocer-Varela J (2013) CTLA-4 and autoimmunity: new insights into the dual regulator of tolerance. Autoimmun Rev 12:1171–1176. doi:10.1016/j.autrev.2013.07.002 CrossRef PubMed
Saff EB, Kuijlaars ABJ (1997) Distributing many points on a sphere. Math Intell 19:5–11. doi:10.1007/BF03024331 CrossRef
Salzmann CA, Olivry TJM, Nielsen DM et al (2011) Genome-wide linkage study of atopic dermatitis in West Highland White Terriers. BMC Genet 12:37. doi:10.1186/1471-2156-12-37 PubMedCentral CrossRef PubMed
Schrauwen I, Barber RM, Schatzberg SJ et al (2014) Identification of novel genetic risk loci in Maltese dogs with necrotizing meningoencephalitis and evidence of a shared genetic risk across toy dog breeds. PLoS One 9, e112755. doi:10.1371/journal.pone.0112755 PubMedCentral CrossRef PubMed
Selmi C, Lu Q, Humble MC (2012) Heritability versus the role of the environment in autoimmunity. J Autoimmun 39:249–252. doi:10.1016/j.jaut.2012.07.011 CrossRef PubMed
Sharma R, Fu SM, Ju S-T (2011) IL-2: a two-faced master regulator of autoimmunity. J Autoimmun 36:91–97. doi:10.1016/j.jaut.2011.01.001 PubMedCentral CrossRef PubMed
Short AD, Saleh NM, Catchpole B et al (2010) CTLA4 promoter polymorphisms are associated with canine diabetes mellitus. Tissue Antigens 75:242–252. doi:10.1111/j.1399-0039.2009.01434.x CrossRef PubMed
Short AD, Boag A, Catchpole B et al (2013) A candidate gene analysis of canine hypoadrenocorticism in 3 dog breeds. J Hered 104:807–820. doi:10.1093/jhered/est051 CrossRef PubMed
Sorrentino R (2013) Genetics of autoimmunity: an update. Immunol Lett 158:116–119. doi:10.1016/j.imlet.2013.12.005 CrossRef PubMed
Stanford SM, Bottini N (2014) PTPN22: the archetypal non-HLA autoimmunity gene. Nat Rev Rheumatol 10:602–611. doi:10.1038/nrrheum.2014.109 PubMedCentral CrossRef PubMed
Temajo NO, Howard N (2014) The mosaic of environment involvement in autoimmunity: the abrogation of viral latency by stress, a non-infectious environmental agent, is an intrinsic prerequisite prelude before viruses can rank as infectious environmental agents that trigger autoimmune diseases. Autoimmun Rev 13:635–640. doi:10.1016/j.autrev.2013.12.003 CrossRef PubMed
Van der Auwera GA, Carneiro MO, Hartl C et al (2013) From FastQ data to high confidence variant calls: the genome analysis toolkit best practices pipeline. Curr Protoc Bioinforma 11:11.10.1–11.10.33. doi:10.1002/0471250953.bi1110s43
Venkataraman GM, Geraghty D, Fox J et al (2013) Canine DLA-79 gene: an improved typing method, identification of new alleles and its role in graft rejection and graft-versus-host disease. Tissue Antigens 81:204–211. doi:10.1111/tan.12094 PubMedCentral CrossRef PubMed
Visscher PM, Brown MA, McCarthy MI, Yang J (2012) Five years of GWAS discovery. Am J Hum Genet 90:7–24. doi:10.1016/j.ajhg.2011.11.029 PubMedCentral CrossRef PubMed
Voight BF, Cotsapas C (2012) Human genetics offers an emerging picture of common pathways and mechanisms in autoimmunity. Curr Opin Immunol 24:552–557. doi:10.1016/j.coi.2012.07.013 CrossRef PubMed
Wang P, Zangerl B, Werner P et al (2011) Familial cutaneous lupus erythematosus (CLE) in the German shorthaired pointer maps to CFA18, a canine orthologue to human CLE. Immunogenetics 63:197–207. doi:10.1007/s00251-010-0499-z PubMedCentral CrossRef PubMed
Weinkle TK, Center SA, Randolph JF et al (2005) Evaluation of prognostic factors, survival rates, and treatment protocols for immune-mediated hemolytic anemia in dogs: 151 cases (1993–2002). J Am Vet Med Assoc 226:1869–1880CrossRef PubMed
Whitley NT, Day MJ (2011) Immunomodulatory drugs and their application to the management of canine immune-mediated disease. J Small Anim Pract 52:70–85. doi:10.1111/j.1748-5827.2011.01024.x CrossRef PubMed
Wilbe M, Jokinen P, Hermanrud C et al (2009) MHC class II polymorphism is associated with a canine SLE-related disease complex. Immunogenetics 61:557–564. doi:10.1007/s00251-009-0387-6 CrossRef PubMed
Wilbe M, Jokinen P, Truvé K et al (2010a) Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex. Nat Genet 42:250–254. doi:10.1038/ng.525 CrossRef PubMed
Wilbe M, Sundberg K, Hansen IR et al (2010b) Increased genetic risk or protection for canine autoimmune lymphocytic thyroiditis in Giant Schnauzers depends on DLA class II genotype. Tissue Antigens 75:712–719. doi:10.1111/j.1399-0039.2010.01449.x CrossRef PubMed
Wilbe M, Ziener ML, Aronsson A et al (2010c) DLA class II alleles are associated with risk for canine symmetrical lupoid onychodystropy (SLO). PLoS One 5, e12332. doi:10.1371/journal.pone.0012332.t004 PubMedCentral CrossRef PubMed
Ymer SI, Huang D, Penna G et al (2002) Polymorphisms in the Il12b gene affect structure and expression of IL-12 in NOD and other autoimmune-prone mouse strains. Genes Immun 3:151–157. doi:10.1038/sj.gene.6363849 CrossRef PubMed - 作者单位：Steven G. Friedenberg (1) (3)
Greg Buhrman (2)
Lhoucine Chdid (1)
Natasha J. Olby (1) (3)
Thierry Olivry (1) (3)
Julien Guillaumin (5)
Theresa O’Toole (6)
Robert Goggs (7)
Lorna J. Kennedy (4)
Robert B. Rose (2) (3)
Kathryn M. Meurs (1) (3)
1. Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27607, USA
3. Comparative Medicine Institute, North Carolina State University, Raleigh, NC, 27607, USA
2. Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, 27695, USA
5. Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, 43210, USA
6. Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, 01536, USA
7. Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA
4. Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK, M13 9PT - 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biomedicine
Immunology
Allergology
Cell Biology - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-1211
文摘
Immune-mediated diseases are common and life-threatening disorders in dogs. Many canine immune-mediated diseases have strong breed predispositions and are believed to be inherited. However, the genetic mutations that cause these diseases are mostly unknown. As many immune-mediated diseases in humans share polymorphisms among a common set of genes, we conducted a candidate gene study of 15 of these genes across four immune-mediated diseases (immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis (IMPA), and atopic dermatitis) in 195 affected and 206 unaffected dogs to assess whether causative or predictive polymorphisms might exist in similar genes in dogs. We demonstrate a strong association (Fisher’s exact p = 0.0004 for allelic association, p = 0.0035 for genotypic association) between two polymorphic positions (10 bp apart) in exon 2 of one allele in DLA-79, DLA-79*001:02, and multiple immune-mediated diseases. The frequency of this allele was significantly higher in dogs with immune-mediated disease than in control dogs (0.21 vs. 0.12) and ranged from 0.28 in dogs with IMPA to 0.15 in dogs with atopic dermatitis. This allele has two non-synonymous substitutions (compared with the reference allele, DLA-79*001:01), resulting in F33L and N37D amino acid changes. These mutations occur in the peptide-binding pocket of the protein, and based upon our computational modeling studies, are likely to affect critical interactions with the peptide N-terminus. Further studies are warranted to confirm these findings more broadly and to determine the specific mechanism by which the identified variants alter canine immune system function.