Advertisement

Immunogenetics

, Volume 66, Issue 5, pp 311–324 | Cite as

Genetics of canine anal furunculosis in the German shepherd dog

  • Jonathan Massey
  • Andrea D. Short
  • Brian Catchpole
  • Arthur House
  • Michael J. Day
  • Hannes Lohi
  • William E. R. Ollier
  • Lorna J. Kennedy
Original Paper

Abstract

Canine anal furunculosis (AF) is characterised by ulceration and fistulation of perianal tissue and is a disease that particularly affects German shepherd dogs (GSDs). There are some similarities between AF and perianal Crohn’s disease (CD) in man. An immune-mediated aetiopathogenesis for AF has been suggested due to tissue pathology, a major histocompatibility complex (MHC) association and clinical response to ciclosporin. Genome-wide association studies (GWAS) can be conducted in dogs with fewer markers and individuals than would be required in a human study. A discovery GWAS was performed on 21 affected and 25 control GSDs from the UK. No SNPs reached genome-wide significance levels at this stage. However, 127 nominally associated SNPs were genotyped in further 76 cases and 191 controls from the UK and Finland. Sequencing of these regions was undertaken to discover novel genetic variation. Association testing of these variants in the UK and Finnish cohorts revealed nine significantly associated SNPs, six of which cause non-synonymous changes in protein sequence. The ADAMTS16 and CTNND2 gene regions were most significantly associated with disease. Members of the butyrophilin protein family, important in intestinal inflammatory regulation, were also associated with disease, but their independence from the MHC region remains to be established. The CTNND2 gene region is also interesting as this locus was implicated in human ulcerative colitis and CD, albeit at a different candidate gene: DAP. We suggest that this represents a common association between inflammatory bowel disease-related conditions in both species and believe that future studies will strengthen this link.

Keywords

Canine anal furunculosis German shepherd dog Crohn’s disease Perianal Inflammatory bowel disease 

Notes

Acknowledgments

We would like to acknowledge the Kennel Club (UK) for funding the GWAS, the American Kennel Club for funding the GWAS replication and sequencing and the University of Manchester for funding the sequencing confirmation study (through an ‘Investing in Success’ award made to JM). We thank Turlough O’Neill for diagnosing many of the UK samples and Hazel Platt for assistance with genotyping. We would also like to extend thanks to the technical staff supporting the UK DNA Archive for Companion Animals.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

251_2014_766_MOESM1_ESM.pdf (143 kb)
ESM 1 (PDF 143 kb)
251_2014_766_MOESM2_ESM.pdf (144 kb)
ESM 2 (PDF 144 kb)
251_2014_766_MOESM3_ESM.pdf (111 kb)
ESM 3 (PDF 110 kb)
251_2014_766_MOESM4_ESM.pdf (159 kb)
ESM 4 (PDF 158 kb)
251_2014_766_MOESM5_ESM.pdf (11 kb)
ESM 5 (PDF 10 kb)
251_2014_766_MOESM6_ESM.pdf (116 kb)
ESM 6 (PDF 116 kb)

References

  1. Alkim H, Ayaz S, Alkim C, Ulker A, Sahin B (2011) Continuous active state of coagulation system in patients with nonthrombotic inflammatory bowel disease. Clin Appl Thromb Hemost 17(6):600–604. doi: 10.1177/1076029611405034 PubMedCrossRefGoogle Scholar
  2. Anderson CA, Boucher G, Lees CW, Franke A, D'Amato M, Taylor KD, Lee JC, Goyette P, Imielinski M, Latiano A, Lagace C, Scott R, Amininejad L, Bumpstead S, Baidoo L, Baldassano RN, Barclay M, Bayless TM, Brand S, Buning C, Colombel JF, Denson LA, De Vos M, Dubinsky M, Edwards C, Ellinghaus D, Fehrmann RS, Floyd JA, Florin T, Franchimont D, Franke L, Georges M, Glas J, Glazer NL, Guthery SL, Haritunians T, Hayward NK, Hugot JP, Jobin G, Laukens D, Lawrance I, Lemann M, Levine A, Libioulle C, Louis E, McGovern DP, Milla M, Montgomery GW, Morley KI, Mowat C, Ng A, Newman W, Ophoff RA, Papi L, Palmieri O, Peyrin-Biroulet L, Panes J, Phillips A, Prescott NJ, Proctor DD, Roberts R, Russell R, Rutgeerts P, Sanderson J, Sans M, Schumm P, Seibold F, Sharma Y, Simms LA, Seielstad M, Steinhart AH, Targan SR, van den Berg LH, Vatn M, Verspaget H, Walters T, Wijmenga C, Wilson DC, Westra HJ, Xavier RJ, Zhao ZZ, Ponsioen CY, Andersen V, Torkvist L, Gazouli M, Anagnou NP, Karlsen TH, Kupcinskas L, Sventoraityte J, Mansfield JC, Kugathasan S, Silverberg MS, Halfvarson J, Rotter JI, Mathew CG, Griffiths AM, Gearry R, Ahmad T, Brant SR, Chamaillard M, Satsangi J, Cho JH, Schreiber S, Daly MJ, Barrett JC, Parkes M, Annese V, Hakonarson H, Radford-Smith G, Duerr RH, Vermeire S, Weersma RK, Rioux JD (2011) Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet 43(3):246–252. doi: 10.1038/ng.764 PubMedCentralPubMedCrossRefGoogle Scholar
  3. Arnett HA, Escobar SS, Viney JL (2009) Regulation of costimulation in the era of butyrophilins. Cytokine 46(3):370–375. doi: 10.1016/j.cyto.2009.03.009 PubMedCrossRefGoogle Scholar
  4. Aulchenko YS, Ripke S, Isaacs A, van Duijn CM (2007) GenABEL: an R library for genome-wide association analysis. Bioinformatics 23(10):1294–1296. doi: 10.1093/bioinformatics/btm108 PubMedCrossRefGoogle Scholar
  5. Barnes A, O'Neill T, Kennedy LJ, Short AD, Catchpole B, House A, Binns M, Fretwell N, Day MJ, Ollier WE (2009) Association of canine anal furunculosis with TNFA is secondary to linkage disequilibrium with DLA-DRB1*. Tissue Antigens 73(3):218–224PubMedCrossRefGoogle Scholar
  6. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265. doi: 10.1093/bioinformatics/bth457 PubMedCrossRefGoogle Scholar
  7. Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, Brant SR, Silverberg MS, Taylor KD, Barmada MM, Bitton A, Dassopoulos T, Datta LW, Green T, Griffiths AM, Kistner EO, Murtha MT, Regueiro MD, Rotter JI, Schumm LP, Steinhart AH, Targan SR, Xavier RJ, Libioulle C, Sandor C, Lathrop M, Belaiche J, Dewit O, Gut I, Heath S, Laukens D, Mni M, Rutgeerts P, Van Gossum A, Zelenika D, Franchimont D, Hugot JP, de Vos M, Vermeire S, Louis E, Cardon LR, Anderson CA, Drummond H, Nimmo E, Ahmad T, Prescott NJ, Onnie CM, Fisher SA, Marchini J, Ghori J, Bumpstead S, Gwilliam R, Tremelling M, Deloukas P, Mansfield J, Jewell D, Satsangi J, Mathew CG, Parkes M, Georges M, Daly MJ (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet 40(8):955–962. doi: 10.1038/ng.175 PubMedCentralPubMedCrossRefGoogle Scholar
  8. Boyko AR (2011) The domestic dog: man's best friend in the genomic era. Genome Biol 12(2):216. doi: 10.1186/gb-2011-12-2-216 PubMedCentralPubMedCrossRefGoogle Scholar
  9. Burger MJ, Tebay MA, Keith PA, Samaratunga HM, Clements J, Lavin MF, Gardiner RA (2002) Expression analysis of delta-catenin and prostate-specific membrane antigen: their potential as diagnostic markers for prostate cancer. Int J Cancer 100(2):228–237. doi: 10.1002/ijc.10468 PubMedCrossRefGoogle Scholar
  10. Day MJ (1993) Immunopathology of Anal Furunculosis in the Dog. J Small Anim Pract 34(8):381–389. doi: 10.1111/j.1748-5827.1993.tb02726.x CrossRefGoogle Scholar
  11. Day MJ, Weaver BMQ (1992) Pathology of surgically resected tissue from 305 cases of anal furunculosis in the dog. J Small Anim Pract 33(12):583–589CrossRefGoogle Scholar
  12. De Strooper B, Saftig P, Craessaerts K, Vanderstichele H, Guhde G, Annaert W, Von Figura K, Van Leuven F (1998) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391(6665):387–390. doi: 10.1038/34910 PubMedCrossRefGoogle Scholar
  13. DeBusk LM, Boelte K, Min Y, Lin PC (2010) Heterozygous deficiency of delta-catenin impairs pathological angiogenesis. J Exp Med 207(1):77–84. doi: 10.1084/jem.20091097 PubMedCentralPubMedCrossRefGoogle Scholar
  14. DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, Philippakis AA, del Angel G, Rivas MA, Hanna M, McKenna A, Fennell TJ, Kernytsky AM, Sivachenko AY, Cibulskis K, Gabriel SB, Altshuler D, Daly MJ (2011) A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet 43(5):491–498. doi: 10.1038/ng.806 PubMedCentralPubMedCrossRefGoogle Scholar
  15. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314(5804):1461–1463PubMedCrossRefGoogle Scholar
  16. Galandiuk S, Kimberling J, Al-Mishlab TG, Stromberg AJ (2005) Perianal Crohn disease: predictors of need for permanent diversion. Ann Surg 241(5):796–801, discussion 801-792PubMedCentralPubMedCrossRefGoogle Scholar
  17. Gopalakrishnan K, Kumarasamy S, Abdul-Majeed S, Kalinoski AL, Morgan EE, Gohara AF, Nauli SM, Filipiak WE, Saunders TL, Joe B (2012) Targeted disruption of Adamts16 gene in a rat genetic model of hypertension. Proc Natl Acad Sci U S A 109(50):20555–20559. doi: 10.1073/pnas.1211290109 PubMedCentralPubMedCrossRefGoogle Scholar
  18. Harkin KR, Walshaw R, Mullaney TP (1996) Association of perianal fistula and colitis in the German shepherd dog: response to high-dose prednisone and dietary therapy. J Am Anim Hosp Assoc 32(6):515–520PubMedGoogle Scholar
  19. He Y, Kim H, Ryu T, Kang Y, Kim JA, Kim BH, Lee JH, Kang K, Lu Q, Kim K (2013) delta-catenin overexpression promotes angiogenic potential of CWR22Rv-1 prostate cancer cells via HIF-1alpha and VEGF. FEBS Lett 587(2):193–199. doi: 10.1016/j.febslet.2012.11.024 PubMedCrossRefGoogle Scholar
  20. House A, Gregory SP, Catchpole B (2003) Expression of cytokine mRNA in canine anal furunculosis lesions. Vet Rec 153(12):354–358PubMedCrossRefGoogle Scholar
  21. House AK, Catchpole B, Gregory SP (2007) Matrix metalloproteinase mRNA expression in canine anal furunculosis lesions. Vet Immunol Immunopathol 115(1–2):68–75. doi: 10.1016/j.vetimm.2006.10.018 PubMedCrossRefGoogle Scholar
  22. House AK, Binns MM, Gregory SP, Catchpole B (2009) Analysis of NOD1, NOD2, TLR1, TLR2, TLR4, TLR5, TLR6 and TLR9 genes in anal furunculosis of German shepherd dogs. Tissue Antigens 73(3):250–254. doi: 10.1111/j.1399-0039.2008.01190.x PubMedCrossRefGoogle Scholar
  23. Hudson M, Chitolie A, Hutton RA, Smith MS, Pounder RE, Wakefield AJ (1996) Thrombotic vascular risk factors in inflammatory bowel disease. Gut 38(5):733–737PubMedCentralPubMedCrossRefGoogle Scholar
  24. Joe B, Saad Y, Dhindaw S, Lee NH, Frank BC, Achinike OH, Luu TV, Gopalakrishnan K, Toland EJ, Farms P, Yerga-Woolwine S, Manickavasagam E, Rapp JP, Garrett MR, Coe D, Apte SS, Rankinen T, Perusse L, Ehret GB, Ganesh SK, Cooper RS, O'Connor A, Rice T, Weder AB, Chakravarti A, Rao DC, Bouchard C (2009) Positional identification of variants of Adamts16 linked to inherited hypertension. Hum Mol Genet 18(15):2825–2838. doi: 10.1093/hmg/ddp218 PubMedCentralPubMedCrossRefGoogle Scholar
  25. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA, Essers J, Mitrovic M, Ning K, Cleynen I, Theatre E, Spain SL, Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L, Ananthakrishnan AN, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, Bitton A, Boucher G, Brand S, Buning C, Cohain A, Cichon S, D'Amato M, De Jong D, Devaney KL, Dubinsky M, Edwards C, Ellinghaus D, Ferguson LR, Franchimont D, Fransen K, Gearry R, Georges M, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, Hedl M, Hu X, Karlsen TH, Kupcinskas L, Kugathasan S, Latiano A, Laukens D, Lawrance IC, Lees CW, Louis E, Mahy G, Mansfield J, Morgan AR, Mowat C, Newman W, Palmieri O, Ponsioen CY, Potocnik U, Prescott NJ, Regueiro M, Rotter JI, Russell RK, Sanderson JD, Sans M, Satsangi J, Schreiber S, Simms LA, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, De Vos M, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhao H, Silverberg MS, Annese V, Hakonarson H, Brant SR, Radford-Smith G, Mathew CG, Rioux JD, Schadt EE, Daly MJ, Franke A, Parkes M, Vermeire S, Barrett JC, Cho JH (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491(7422):119–124. doi: 10.1038/nature11582 PubMedCentralPubMedCrossRefGoogle Scholar
  26. Kabi A, Nickerson KP, Homer CR, McDonald C (2012) Digesting the genetics of inflammatory bowel disease: insights from studies of autophagy risk genes. Inflamm Bowel Dis 18(4):782–792. doi: 10.1002/ibd.21868 PubMedCentralPubMedCrossRefGoogle Scholar
  27. Karlsson EK, Baranowska I, Wade CM, Salmon Hillbertz NH, Zody MC, Anderson N, Biagi TM, Patterson N, Pielberg GR, Kulbokas EJ 3rd, Comstock KE, Keller ET, Mesirov JP, von Euler H, Kampe O, Hedhammar A, Lander ES, Andersson G, Andersson L, Lindblad-Toh K (2007) Efficient mapping of mendelian traits in dogs through genome-wide association. Nat Genet 39(11):1321–1328PubMedCrossRefGoogle Scholar
  28. Kennedy LJ, O'Neill T, House A, Barnes A, Kyostila K, Innes J, Fretwell N, Day MJ, Catchpole B, Lohi H, Ollier WE (2008) Risk of anal furunculosis in German shepherd dogs is associated with the major histocompatibility complex. Tissue Antigens 71(1):51–56PubMedGoogle Scholar
  29. Koren I, Reem E, Kimchi A (2010) DAP1, a novel substrate of mTOR, negatively regulates autophagy. Curr Biol 20(12):1093–1098. doi: 10.1016/j.cub.2010.04.041 PubMedCrossRefGoogle Scholar
  30. Li H (2011) Improving SNP discovery by base alignment quality. Bioinformatics 27(8):1157–1158. doi: 10.1093/bioinformatics/btr076 PubMedCentralPubMedCrossRefGoogle Scholar
  31. Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25(14):1754–1760. doi: 10.1093/bioinformatics/btp324 PubMedCentralPubMedCrossRefGoogle Scholar
  32. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R, Proc GPD (2009) The Sequence Alignment/Map format and SAMtools. Bioinformatics 25(16):2078–2079. doi: 10.1093/bioinformatics/btp352 PubMedCentralPubMedCrossRefGoogle Scholar
  33. Lindblad-Toh K, Wade CM, Mikkelsen TS, Karlsson EK, Jaffe DB, Kamal M, Clamp M, Chang JL, Kulbokas EJ 3rd, Zody MC, Mauceli E, Xie X, Breen M, Wayne RK, Ostrander EA, Ponting CP, Galibert F, Smith DR, DeJong PJ, Kirkness E, Alvarez P, Biagi T, Brockman W, Butler J, Chin CW, Cook A, Cuff J, Daly MJ, DeCaprio D, Gnerre S, Grabherr M, Kellis M, Kleber M, Bardeleben C, Goodstadt L, Heger A, Hitte C, Kim L, Koepfli KP, Parker HG, Pollinger JP, Searle SM, Sutter NB, Thomas R, Webber C, Baldwin J, Abebe A, Abouelleil A, Aftuck L, Ait-Zahra M, Aldredge T, Allen N, An P, Anderson S, Antoine C, Arachchi H, Aslam A, Ayotte L, Bachantsang P, Barry A, Bayul T, Benamara M, Berlin A, Bessette D, Blitshteyn B, Bloom T, Blye J, Boguslavskiy L, Bonnet C, Boukhgalter B, Brown A, Cahill P, Calixte N, Camarata J, Cheshatsang Y, Chu J, Citroen M, Collymore A, Cooke P, Dawoe T, Daza R, Decktor K, DeGray S, Dhargay N, Dooley K, Dooley K, Dorje P, Dorjee K, Dorris L, Duffey N, Dupes A, Egbiremolen O, Elong R, Falk J, Farina A, Faro S, Ferguson D, Ferreira P, Fisher S, FitzGerald M, Foley K, Foley C, Franke A, Friedrich D, Gage D, Garber M, Gearin G, Giannoukos G, Goode T, Goyette A, Graham J, Grandbois E, Gyaltsen K, Hafez N, Hagopian D, Hagos B, Hall J, Healy C, Hegarty R, Honan T, Horn A, Houde N, Hughes L, Hunnicutt L, Husby M, Jester B, Jones C, Kamat A, Kanga B, Kells C, Khazanovich D, Kieu AC, Kisner P, Kumar M, Lance K, Landers T, Lara M, Lee W, Leger JP, Lennon N, Leuper L, LeVine S, Liu J, Liu X, Lokyitsang Y, Lokyitsang T, Lui A, Macdonald J, Major J, Marabella R, Maru K, Matthews C, McDonough S, Mehta T, Meldrim J, Melnikov A, Meneus L, Mihalev A, Mihova T, Miller K, Mittelman R, Mlenga V, Mulrain L, Munson G, Navidi A, Naylor J, Nguyen T, Nguyen N, Nguyen C, Nguyen T, Nicol R, Norbu N, Norbu C, Novod N, Nyima T, Olandt P, O'Neill B, O'Neill K, Osman S, Oyono L, Patti C, Perrin D, Phunkhang P, Pierre F, Priest M, Rachupka A, Raghuraman S, Rameau R, Ray V, Raymond C, Rege F, Rise C, Rogers J, Rogov P, Sahalie J, Settipalli S, Sharpe T, Shea T, Sheehan M, Sherpa N, Shi J, Shih D, Sloan J, Smith C, Sparrow T, Stalker J, Stange-Thomann N, Stavropoulos S, Stone C, Stone S, Sykes S, Tchuinga P, Tenzing P, Tesfaye S, Thoulutsang D, Thoulutsang Y, Topham K, Topping I, Tsamla T, Vassiliev H, Venkataraman V, Vo A, Wangchuk T, Wangdi T, Weiand M, Wilkinson J, Wilson A, Yadav S, Yang S, Yang X, Young G, Yu Q, Zainoun J, Zembek L, Zimmer A, Lander ES (2005) Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 438(7069):803–819PubMedCrossRefGoogle Scholar
  34. Lu Q, Paredes M, Medina M, Zhou J, Cavallo R, Peifer M, Orecchio L, Kosik KS (1999) delta-catenin, an adhesive junction-associated protein which promotes cell scattering. J Cell Biol 144(3):519–532PubMedCentralPubMedCrossRefGoogle Scholar
  35. Lu Q, Dobbs LJ, Gregory CW, Lanford GW, Revelo MP, Shappell S, Chen YH (2005) Increased expression of delta-catenin/neural plakophilin-related armadillo protein is associated with the down-regulation and redistribution of E-cadherin and p120ctn in human prostate cancer. Hum Pathol 36(10):1037–1048. doi: 10.1016/j.humpath.2005.07.012 PubMedCrossRefGoogle Scholar
  36. Mathews KA, Sukhiani HR (1997) Randomized controlled trial of cyclosporine for treatment of perianal fistulas in dogs. J Am Vet Med Assoc 211(10):1249–1253PubMedGoogle Scholar
  37. Mathews KA, Ayres SA, Tano CA, Riley SM, Sukhiani HR, Adams C (1997) Cyclosporin treatment of perianal fistulas in dogs. Can Vet J 38(1):39–41PubMedCentralPubMedGoogle Scholar
  38. Orozco G, Eerligh P, Sanchez E, Zhernakova S, Roep BO, Gonzalez-Gay MA, Lopez-Nevot MA, Callejas JL, Hidalgo C, Pascual-Salcedo D, Balsa A, Gonzalez-Escribano MF, Koeleman BP, Martin J (2005) Analysis of a functional BTNL2 polymorphism in type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus. Hum Immunol 66(12):1235–1241. doi: 10.1016/j.humimm.2006.02.003 PubMedCrossRefGoogle Scholar
  39. Pesu M, Watford WT, Wei L, Xu LL, Fuss I, Strober W, Andersson J, Shevach EM, Quezado M, Bouladoux N, Roebroek A, Belkaid Y, Creemers J, O'Shea JJ (2008) T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance. Nature 455(7210):246. doi: 10.1038/Nature07210 Google Scholar
  40. Porter S, Clark IM, Kevorkian L, Edwards DR (2005) The ADAMTS metalloproteinases. Biochem J 386(Pt 1):15–27. doi: 10.1042/BJ20040424 PubMedCentralPubMedGoogle Scholar
  41. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, Maller J, Sklar P, de Bakker PIW, Daly MJ, Sham PC (2007) PLINK: A tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559–575. doi: 10.1086/519795 PubMedCentralPubMedCrossRefGoogle Scholar
  42. Rath T, Roderfeld M, Graf J, Wagner S, Vehr AK, Dietrich C, Geier A, Roeb E (2006) Enhanced expression of MMP-7 and MMP-13 in inflammatory bowel disease: a precancerous potential? Inflamm Bowel Dis 12(11):1025–1035. doi: 10.1097/01.mib.0000234133.97594.04 PubMedCrossRefGoogle Scholar
  43. Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, Green T, Kuballa P, Barmada MM, Datta LW, Shugart YY, Griffiths AM, Targan SR, Ippoliti AF, Bernard EJ, Mei L, Nicolae DL, Regueiro M, Schumm LP, Steinhart AH, Rotter JI, Duerr RH, Cho JH, Daly MJ, Brant SR (2007) Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 39(5):596–604. doi: 10.1038/ng2032 PubMedCentralPubMedCrossRefGoogle Scholar
  44. Rybicki BA, Walewski JL, Maliarik MJ, Kian H, Iannuzzi MC (2005) The BTNL2 gene and sarcoidosis susceptibility in African Americans and Whites. Am J Hum Genet 77(3):491–499. doi: 10.1086/444435 PubMedCentralPubMedCrossRefGoogle Scholar
  45. Sandborn WJ, Fazio VW, Feagan BG, Hanauer SB (2003) AGA technical review on perianal Crohn's disease. Gastroenterology 125(5):1508–1530PubMedCrossRefGoogle Scholar
  46. Stanley BJ, Hauptman JG (2009) Long-term prospective evaluation of topically applied 0.1 % tacrolimus ointment for treatment of perianal sinuses in dogs. J Am Vet Med Assoc 235(4):397–404. doi: 10.2460/javma.235.4.397 PubMedCrossRefGoogle Scholar
  47. Surridge AK, Rodgers UR, Swingler TE, Davidson RK, Kevorkian L, Norton R, Waters JG, Goldring MB, Parker AE, Clark IM (2009) Characterization and regulation of ADAMTS-16. Matrix Biol 28(7):416–424. doi: 10.1016/j.matbio.2009.07.001 PubMedCentralPubMedCrossRefGoogle Scholar
  48. Tengvall K, Kierczak M, Bergvall K, Olsson M, Frankowiack M, Farias FH, Pielberg G, Carlborg O, Leeb T, Andersson G, Hammarstrom L, Hedhammar A, Lindblad-Toh K (2013) Genome-wide analysis in German shepherd dogs reveals association of a locus on CFA 27 with atopic dermatitis. PLoS Genet 9(5):e1003475. doi: 10.1371/journal.pgen.1003475 PubMedCentralPubMedCrossRefGoogle Scholar
  49. Tivers MS, Catchpole B, Gregory SP, House AK (2008) Interleukin-2 and interferon-gamma mRNA expression in canine anal furunculosis lesions and the effect of ciclosporin therapy. Vet Immunol Immunopathol 125(1–2):31–36. doi: 10.1016/j.vetimm.2008.04.018 PubMedCrossRefGoogle Scholar
  50. Vatn M (2012) Environmental factors in the epidemiology of inflammatory bowel disease. In: Baumgart DC (ed) Crohn’s Disease and ulcerative colitis. Springer, US, pp 17–38. doi: 10.1007/978-1-4614-0998-4_2 CrossRefGoogle Scholar
  51. Vizoso FJ, Gonzalez LO, Corte MD, Corte MG, Bongera M, Martinez A, Martin A, Andicoechea A, Gava RR (2006) Collagenase-3 (MMP-13) expression by inflamed mucosa in inflammatory bowel disease. Scand J Gastroenterol 41(9):1050–1055. doi: 10.1080/00365520600554667 PubMedCrossRefGoogle Scholar
  52. Wang K, Li M, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38(16):e164. doi: 10.1093/nar/gkq603 PubMedCentralPubMedCrossRefGoogle Scholar
  53. Wilbe M, Jokinen P, Truve K, Seppala EH, Karlsson EK, Biagi T, Hughes A, Bannasch D, Andersson G, Hansson-Hamlin H, Lohi H, Lindblad-Toh K (2010) Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex. Nat Genet 42(3):250–254. doi: 10.1038/ng.525 PubMedCrossRefGoogle Scholar
  54. Xiao R, Boehnke M (2009) Quantifying and correcting for the winner's curse in genetic association studies. Genet Epidemiol 33(5):453–462. doi: 10.1002/gepi.20398 PubMedCentralPubMedCrossRefGoogle Scholar
  55. Zeng Y, Abdallah A, Lu JP, Wang T, Chen YH, Terrian DM, Kim K, Lu Q (2009) delta-Catenin promotes prostate cancer cell growth and progression by altering cell cycle and survival gene profiles. Mol Cancer 8:19. doi: 10.1186/1476-4598-8-19 PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Jonathan Massey
    • 1
  • Andrea D. Short
    • 1
  • Brian Catchpole
    • 2
  • Arthur House
    • 3
    • 7
  • Michael J. Day
    • 4
  • Hannes Lohi
    • 5
    • 6
  • William E. R. Ollier
    • 1
  • Lorna J. Kennedy
    • 1
  1. 1.Centre for Integrated Genomic Medical Research (CIGMR), Institute of Population Health, Faculty of Medical and Human SciencesUniversity of ManchesterManchesterUK
  2. 2.Department of Pathology and Infectious Diseases, Royal Veterinary CollegeUniversity of LondonHatfieldUK
  3. 3.Department of Veterinary Clinical Sciences, Royal Veterinary CollegeUniversity of LondonHatfieldUK
  4. 4.School of Veterinary SciencesUniversity of BristolBristolUK
  5. 5.Department of Veterinary Biosciences, Research Programs Unit, Molecular NeurologyUniversity of HelsinkiHelsinkiFinland
  6. 6.The Folkhälsan Institute of GeneticsHelsinkiFinland
  7. 7.Centre for Animal Referral and EmergencyCollingwoodAustralia

Personalised recommendations