Population Genomics of Domestication and Breed Development in Canines in the Context of Cognitive, Social, Behavioral, and Disease Traits

  • Kristopher J. L. IrizarryEmail author
  • Elton J. R. Vasconcelos
Part of the Population Genomics book series (POGE)


Dogs are unique because they are known to be the first species domesticated by humans, have the greatest morphological variation among terrestrial mammals, and exhibit unique bonds with humans. Yet, until very recently, the history of domestication and the associated consequences of this artificial selection have been a matter of speculation. Domesticated dogs are the ideal organism to study population genomics of domestication and the impact artificial selection has had on cognitive, social, behavioral, and disease traits. Because dogs have been associated with humans for tens of thousands of years, they are uniquely suited to investigate the genetic basis of selection for dietary adaptation during the agricultural revolution. Through a variety of large-scale genomics approaches, the history and consequences of dog domestication are no longer a matter of speculation. This chapter delves into the ancient origins of human-canine interactions and follows the domestication of wolves into dogs with a particular focus on (a) the selection of phenotypes underlying the strong bond between humans and their companion dogs, (b) the morphological variation underlying dog breeds, and (c) the genetic basis of canine diseases. The historical picture that is beginning to emerge provides a genomics framework for understanding why and how the dog became “our best friend.”


Behavioral phenotypes Canine Canine genetic diseases Cognitive phenotypes Disease phenotypes Dog breeding Dog breeds Domestication Genomics Human-animal bond 



Dr. Irizarry acknowledges the role his father and mother had in inspiring him to write this chapter by introducing Dr. Irizarry to the human-animal bond through special relationships with family dogs. Furthermore, Dr. Irizarry wishes to acknowledge the many conversations he had with his parents about cognition, dogs, domestication, and what makes dogs “our best friend.” Those experiences and conversations ultimately paved the path to this chapter. The authors thank Dr. Om Rajora for reading the manuscript and making suggestions during the editing process. Dr. Rajora is acknowledged for simplifying, helping improve text, and favorably upgrading canine knowledge in our chapter. The authors wish to thank Chris Vander Veen for taking time to help prepare documents, without which, this chapter could not be published. The authors are most thankful for the invention of computers, the Internet, word processing programs, and internet-accessible storage platforms which have greatly enhanced collaborative production and sharing of this chapter. The authors fully recognize the hard work of all the people who contributed to the IT environment at Western University of Health Sciences and on Earth. Their commitment to technology ultimately allowed this chapter to be created and reviewed across multiple countries. Without their hard work, this chapter would never see the light of day. The authors are also most appreciative of the hundreds of veterinarians, doctors, scientists, and authors that have published the papers and figures that contributed to the content of this chapter. We truly thank, respect, and value each one of you. Finally, the authors would like to acknowledge the wonderful dogs each of us has known that have inspired and motivated us to learn more about their origins, their health, and their cognition.


  1. Ahonen SJ, Kaukonen M, Nussdorfer FD, Harman CD, Komaromy AM, Lohi H. A novel missense mutation in ADAMTS10 in Norwegian Elkhound primary glaucoma. PLoS One. 2014;9:e111941.CrossRefGoogle Scholar
  2. Appleyard SM, Hayward M, Young JI, Butler AA, Cone RD, Rubinstein M, Low MJ. A role for the endogenous opioid beta-endorphin in energy homeostasis. Endocrinology. 2003;144:1753–60.CrossRefGoogle Scholar
  3. Arendt M, Fall T, Lindblad-Toh K, Axelsson E. Amylase activity is associated with AMY2B copy numbers in dog: implications for dog domestication, diet and diabetes. Anim Genet. 2014;45:716–22.CrossRefGoogle Scholar
  4. Arendt ML, Melin M, Tonomura N, Koltookian M, Courtay-Cahen C, Flindall N, Bass J, Boerkamp K, Megquir K, Youell L, Murphy S, McCarthy C, London C, Rutteman GR, Starkey M, Lindblad-Toh K. Genome-wide association study of golden retrievers identifies germ-line risk factors predisposing to mast cell tumours. PLoS Genet. 2015;11:e1005647.CrossRefGoogle Scholar
  5. Arendt M, Cairns KM, Ballard JW, Savolainen P, Axelsson E. Diet adaptation in dog reflects spread of prehistoric agriculture. Heredity (Edinb). 2016;117:301–6.CrossRefGoogle Scholar
  6. Axelsson E, Ratnakumar A, Arendt ML, Maqbool K, Webster MT, Perloski M, Liberg O, Arnemo JM, Hedhammar A, Lindblad-Toh K. The genomic signature of dog domestication reveals adaptation to a starch-rich diet. Nature. 2013;495:360–4.CrossRefGoogle Scholar
  7. Bannasch D, Young A, Myers J, Truvé K, Dickinson P, Gregg J, Davis R, Bongcam-Rudloff E, Webster MT, Lindblad-Toh K, Pedersen N. Localization of canine brachycephaly using an across breed mapping approach. PLoS One. 2010;5:e9632.CrossRefGoogle Scholar
  8. Barrientos LS, Zapata G, Crespi JA, Posik DM, Díaz S, It V, Peral-García P, Giovambattista G. A study of the association between chronic superficial keratitis and polymorphisms in the upstream regulatory regions of DLA-DRB1, DLA-DQB1 and DLA-DQA1. Vet Immunol Immunopathol. 2013;156:205–10.CrossRefGoogle Scholar
  9. Bauer A, Waluk DP, Galichet A, Timm K, Jagannathan V, Sayar BS, Wiener DJ, Dietschi E, Müller EJ, Roosje P, Welle MM, Leeb T. A de novo variant in the ASPRV1 gene in a dog with ichthyosis. PLoS Genet. 2017;13:e1006651.CrossRefGoogle Scholar
  10. Bence M, Marx P, Szantai E, Kubinyi E, Ronai Z, Banlaki Z. Lessons from the canine Oxtr gene: populations, variants and functional aspects. Genes Brain Behav. 2017;16:427–38.CrossRefGoogle Scholar
  11. Borge KS, Nord S, Van Loo P, Lingjærde OC, Gunnes G, Alnæs GI, Solvang HK, Lüders T, Kristensen VN, Børresen-Dale AL, Lingaas F. Canine mammary tumours are affected by frequent copy number aberrations, including amplification of MYC and loss of PTEN. PLoS One. 2015;10:e0126371.CrossRefGoogle Scholar
  12. Boyko AR, et al. A simple genetic architecture underlies morphological variation in dogs. PLoS Biol. 2010;8:e1000451.CrossRefGoogle Scholar
  13. Cagan A, Blass T. Identification of genomic variants putatively targeted by selection during dog domestication. BMC Evol Biol. 2016;16:10.CrossRefGoogle Scholar
  14. Challis BG, Pritchard LE, Creemers JW, Delplanque J, Keogh JM, Luan J, Wareham NJ, Yeo GS, Bhattacharyya S, Froguel P, White A, Farooqi IS, O’Rahilly S. A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism. Hum Mol Genet. 2002;11:1997–2004.CrossRefGoogle Scholar
  15. Christopherson PW, Bacek LM, King KB, Boudreaux MK. Two novel missense mutations associated with hemophilia A in a family of Boxers, and a German Shepherd dog. Vet Clin Pathol. 2014;43:312–6.CrossRefGoogle Scholar
  16. Cooper AE, Ahonen S, Rowlan JS, Duncan A, Seppälä EH, Vanhapelto P, Lohi H, Komáromy AM. A novel form of progressive retinal atrophy in Swedish vallhund dogs. PLoS One. 2014;9:e106610.CrossRefGoogle Scholar
  17. Downs LM, Wallin-Håkansson B, Boursnell M, Marklund S, Hedhammar Å, Truvé K, Hübinette L, Lindblad-Toh K, Bergström T, Mellersh CS. A frameshift mutation in golden retriever dogs with progressive retinal atrophy endorses SLC4A3 as a candidate gene for human retinal degenerations. PLoS One. 2011;6:e21452.CrossRefGoogle Scholar
  18. Downs LM, Hitti R, Pregnolato S, Mellersh CS. Genetic screening for PRA-associated mutations in multiple dog breeds shows that PRA is heterogeneous within and between breeds. Vet Ophthalmol. 2014;17:126–30.CrossRefGoogle Scholar
  19. Drogemuller M, Jagannathan V, Dolf G, Butenhoff K, Kottmann-Berger S, Wess G, Leeb T. A single codon insertion in the PICALM gene is not associated with subvalvular aortic stenosis in Newfoundland dogs. Hum Genet. 2015;134:127–9.CrossRefGoogle Scholar
  20. Feldman R. The neurobiology of human attachments. Trends Cogn Sci. 2017;21:80–99.CrossRefGoogle Scholar
  21. Ferraresso S, et al. Epigenetic silencing of TFPI-2 in canine diffuse large B-cell lymphoma. PLoS One. 2014;9:e92707.CrossRefGoogle Scholar
  22. Freedman AH, et al. Genome sequencing highlights the dynamic early history of dogs. PLoS Genet. 2014;10:e1004016.CrossRefGoogle Scholar
  23. Haas MA, Ngo L, Li SS, Schleich S, Qu Z, Vanyai HK, Cullen HD, Cardona-Alberich A, Gladwyn-Ng IE, Pagnamenta AT, Taylor JC, Stewart H, Kini U, Duncan KE, Teleman AA, Keays DA, Heng JI. De novo mutations in DENR disrupt neuronal development and link congenital neurological disorders to faulty mRNA translation re-initiation. Cell Rep. 2016;15:2251–65.CrossRefGoogle Scholar
  24. Hejjas K, Vas J, Topal J, Szantai E, Ronai Z, Szekely A, Kubinyi E, Horvath Z, Sasvari-Szekely M, Miklosi A. Association of polymorphisms in the dopamine D4 receptor gene and the activity-impulsivity endophenotype in dogs. Anim Genet. 2007;38:629–33.CrossRefGoogle Scholar
  25. Holder AL, Price JA, Adams JP, Volk HA, Catchpole B. A retrospective study of the prevalence of the canine degenerative myelopathy associated superoxide dismutase 1 mutation (SOD1:c.118G > A) in a referral population of German Shepherd dogs from the UK. Canine Genet Epidemiol. 2016;1:10.CrossRefGoogle Scholar
  26. Howrigan DP, Simonson MA, Keller MC. Detecting autozygosity through runs of homozygosity: a comparison of three autozygosity detection algorithms. BMC Genomics. 2011;12:460.CrossRefGoogle Scholar
  27. Karyadi DM, Karlins E, Decker B, vonHoldt BM, Carpintero-Ramirez G, Parker HG, Wayne RK, Ostrander EA. A copy number variant at the KITLG locus likely confers risk for canine squamous cell carcinoma of the digit. PLoS Genet. 2013;9:e1003409.CrossRefGoogle Scholar
  28. Kathrani A, House A, Catchpole B, Murphy A, German A, Werling D, Allenspach K. Polymorphisms in the TLR4 and TLR5 gene are significantly associated with inflammatory bowel disease in German Shepherd dogs. PLoS One. 2010;5:e15740.CrossRefGoogle Scholar
  29. Kathrani A, Lee H, White C, Catchpole B, Murphy A, German A, Werling D, Allenspach K. Association between nucleotide oligomerisation domain two (Nod2) gene polymorphisms and canine inflammatory bowel disease. Vet Immunol Immunopathol. 2014;161:32–41.CrossRefGoogle Scholar
  30. Kirkness EF, Bafna V, Halpern AL, Levy S, Remington K, Rusch DB, Delcher AL, Pop M, Wang W, Fraser CM, Venter JC. The dog genome: survey sequencing and comparative analysis. Science. 2003;301:1898–903.CrossRefGoogle Scholar
  31. Kis A, Bence M, Lakatos G, Pergel E, Turcsán B, Pluijmakers J, Vas J, Elek Z, Brúder I, Földi L, Sasvári-Székely M, Miklósi A, Rónai Z, Kubinyi E. Oxytocin receptor gene polymorphisms are associated with human directed social behavior in dogs (Canis familiaris). PLoS One. 2014;9:e83993.CrossRefGoogle Scholar
  32. Kovacs K, Kis A, Pogany A, Koller D, Topal J. Differential effects of oxytocin on social sensitivity in two distinct breeds of dogs (Canis familiaris). Psychoneuroendocrinology. 2016;74:212–20.CrossRefGoogle Scholar
  33. Kubinyi E, Vas J, Hejjas K, Ronai Z, Brúder I, Turcsán B, Sasvari-Szekely M, Miklósi A. Polymorphism in the tyrosine hydroxylase (TH) gene is associated with activity-impulsivity in German Shepherd dogs. PLoS One. 2012;7:e30271.CrossRefGoogle Scholar
  34. Kuchtey J, Kunkel J, Esson D, Sapienza JS, Ward DA, Plummer CE, Gelatt KN, Kuchtey RW. Screening ADAMTS10 in dog populations supports Gly661Arg as the glaucoma-causing variant in beagles. Invest Ophthalmol Vis Sci. 2013;54:1881–6.CrossRefGoogle Scholar
  35. Lee YS, Challis BG, Thompson DA, Yeo GS, Keogh JM, Madonna ME, Wraight V, Sims M, Vatin V, Meyre D, Shield J, Burren C, Ibrahim Z, Cheetham T, Swift P, Blackwood A, Hung CC, Wareham NJ, Froguel P, Millhauser GL, O’Rahilly S, Farooqi IS. A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balance. Cell Metab. 2006;3:135–40.CrossRefGoogle Scholar
  36. Lee EJ, Merriwether DA, Kasparov AK, Nikolskiy PA, Sotnikova MV, Pavlova EY, Pitulko VV. Ancient DNA analysis of the oldest canid species from the Siberian Arctic and genetic contribution to the domestic dog. PLoS One. 2015;10:e0125759.CrossRefGoogle Scholar
  37. Li Y, Vonholdt BM, Reynolds A, Boyko AR, Wayne RK, Wu DD, Zhang YP. Artificial selection on brain-expressed genes during the domestication of dog. Mol Biol Evol. 2013;30:1867–76.CrossRefGoogle Scholar
  38. Li Y, Wang GD, Wang MS, Irwin DM, Wu DD, Zhang YP. Domestication of the dog from the wolf was promoted by enhanced excitatory synaptic plasticity: a hypothesis. Genome Biol Evol. 2014;6:3115–21.CrossRefGoogle Scholar
  39. 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, PJ DJ, 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. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature. 2005;438:803–19.CrossRefGoogle Scholar
  40. Lingaas F, Comstock KE, Kirkness EF, Sørensen A, Aarskaug T, Hitte C, Nickerson ML, Moe L, Schmidt LS, Thomas R, Breen M, Galibert F, Zbar B, Ostrander EA. A mutation in the canine BHD gene is associated with hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis in the German Shepherd dog. Hum Mol Genet. 2003;12:3043–53.CrossRefGoogle Scholar
  41. Massey J, Short AD, Catchpole B, House A, Day MJ, Lohi H, Ollier WE, Kennedy LJ. Genetics of canine anal furunculosis in the German Shepherd dog. Immunogenetics. 2014;66:311–24.CrossRefGoogle Scholar
  42. Melin M, Rivera P, Arendt M, Elvers I, Murén E, Gustafson U, Starkey M, Borge KS, Lingaas F, Häggström J, Saellström S, Rönnberg H, Lindblad-Toh K. Genome-wide analysis identifies germ-line risk factors associated with canine mammary tumours. PLoS Genet. 2016;12:e1006029.CrossRefGoogle Scholar
  43. Meurs KM, Lahmers S, Keene BW, White SN, Oyama MA, Mauceli E, Lindblad-Toh K. A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher. Hum Genet. 2012;131:1319–25.CrossRefGoogle Scholar
  44. Monteagudo LV, Tejedor MT. The b(c) allele of TYRP1 is causative for the recessive brown (liver) colour in German Shepherd dogs. Anim Genet. 2015;46:588–9.CrossRefGoogle Scholar
  45. Mosher DS, Quignon P, Bustamante CD, Sutter NB, Mellersh CS, Parker HG, Ostrander EA. A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs. PLoS Genet. 2007;3:e79.CrossRefGoogle Scholar
  46. Nagasawa M, Mitsui S, En S, Ohtani N, Ohta M, Sakuma Y, Onaka T, Mogi K, Kikusui T. Social evolution. Oxytocin-gaze positive loop and the coevolution of human-dog bonds. Science. 2015;348:333–6.CrossRefGoogle Scholar
  47. Oliver JA, Forman OP, Pettitt L, Mellersh CS. Two independent mutations in ADAMTS17 are associated with primary open angle glaucoma in the Basset Hound and Basset Fauve de Bretagne breeds of dog. PLoS One. 2015;10:e0140436.CrossRefGoogle Scholar
  48. Ovodov ND, Crockford SJ, Kuzmin YV, Higham TF, Hodgins GW, van der Plicht J. A 33,000-year-old incipient dog from the Altai Mountains of Siberia: evidence of the earliest domestication disrupted by the last glacial maximum. PLoS One. 2011;6:e22821.CrossRefGoogle Scholar
  49. Parker HG, Ostrander EA. Canine genomics and genetics: running with the pack. PLoS Genet. 2005;1:e58.CrossRefGoogle Scholar
  50. Persson ME, Wright D, Roth LS, Batakis P, Jensen P. Genomic regions associated with interspecies communication in dogs contain genes related to human social disorders. Sci Rep. 2016;6:33439.CrossRefGoogle Scholar
  51. Philipp U, Vollmar A, Haggstrom J, Thomas A, Distl O. Multiple Loci are associated with dilated cardiomyopathy in Irish wolfhounds. PLoS One. 2012;7:e36691.CrossRefGoogle Scholar
  52. Quignon P, Herbin L, Cadieu E, Kirkness EF, Hédan B, Mosher DS, Galibert F, André C, Ostrander EA, Hitte C. Canine population structure: assessment and impact of intra-breed stratification on SNP-based association studies. PLoS One. 2007;2:e1324.CrossRefGoogle Scholar
  53. Raffan E, Dennis RJ, O’Donovan CJ, Becker JM, Scott RA, Smith SP, Withers DJ, Wood CJ, Conci E, Clements DN, Summers KM, German AJ, Mellersh CS, Arendt ML, Iyemere VP, Withers E, Söder J, Wernersson S, Andersson G, Lindblad-Toh K, Yeo GS, O’Rahilly S. A deletion in the canine POMC gene is associated with weight and appetite in obesity-prone labrador retriever dogs. Cell Metab. 2016;23:893–900.CrossRefGoogle Scholar
  54. Reiter T, Jagoda E, Capellini TD. Dietary variation and evolution of gene copy number among dog breeds. PLoS One. 2016;11:e0148899.CrossRefGoogle Scholar
  55. Romero T, Nagasawa M, Mogi K, Hasegawa T, Kikusui T. Oxytocin promotes social bonding in dogs. Proc Natl Acad Sci U S A. 2014;111:9085–90.CrossRefGoogle Scholar
  56. Saetre P, Lindberg J, Leonard JA, Olsson K, Pettersson U, Ellegren H, Bergström TF, Vilà C, Jazin E. From wild wolf to domestic dog: gene expression changes in the brain. Brain Res Mol Brain Res. 2004;126:198–206.CrossRefGoogle Scholar
  57. Schoenebeck JJ, Hutchinson SA, Byers A, Beale HC, Carrington B, Faden DL, Rimbault M, Decker B, Kidd JM, Sood R, Boyko AR, Fondon JW 3rd, Wayne RK, Bustamante CD, Ciruna B, Ostrander EA. Variation of BMP3 contributes to dog breed skull diversity. PLoS Genet. 2012;8:e1002849.CrossRefGoogle Scholar
  58. Shannon LM, Boyko RH, Castelhano M, Corey E, Hayward JJ, McLean C, White ME, Abi Said M, Anita BA, Bondjengo NI, Calero J, Galov A, Hedimbi M, Imam B, Khalap R, Lally D, Masta A, Oliveira KC, Pérez L, Randall J, Tam NM, Trujillo-Cornejo FJ, Valeriano C, Sutter NB, Todhunter RJ, Bustamante CD, Boyko AR. Genetic structure in village dogs reveals a Central Asian domestication origin. Proc Natl Acad Sci U S A. 2015;112:13639–44.CrossRefGoogle Scholar
  59. Shearin AL, Ostrander EA. Canine morphology: hunting for genes and tracking mutations. PLoS Biol. 2010;8:e1000310.CrossRefGoogle Scholar
  60. Stern JA, White SN, Lehmkuhl LB, Reina-Doreste Y, Ferguson JL, Nascone-Yoder NM, Meurs KM. A single codon insertion in PICALM is associated with development of familial subvalvular aortic stenosis in Newfoundland dogs. Hum Genet. 2014;133:1139–48.CrossRefGoogle Scholar
  61. Stern JA, Hsue W, Song KH, Ontiveros ES, Luis Fuentes V, Stepien RL. Severity of mitral valve degeneration is associated with chromosome 15 loci in whippet dogs. PLoS One. 2015;10:e0141234.CrossRefGoogle Scholar
  62. Tengvall K, Kierczak M, Bergvall K, Olsson M, Frankowiack M, Farias FH, Pielberg G, Carlborg Ö, Leeb T, Andersson G, Hammarström L, Hedhammar Å, Lindblad-Toh K. Genome-wide analysis in German Shepherd dogs reveals association of a locus on CFA 27 with atopic dermatitis. PLoS Genet. 2013;9:e1003475.CrossRefGoogle Scholar
  63. Tengvall K, Kozyrev S, Kierczak M, Bergvall K, Farias FH, Ardesjö-Lundgren B, Olsson M, Murén E, Hagman R, Leeb T, Pielberg G, Hedhammar Å, Andersson G, Lindblad-Toh K. Multiple regulatory variants located in cell type-specific enhancers within the PKP2 locus form major risk and protective haplotypes for canine atopic dermatitis in German Shepherd dogs. BMC Genet. 2016;17:97.CrossRefGoogle Scholar
  64. Thalmann O, Shapiro B, Cui P, Schuenemann VJ, Sawyer SK, Greenfield DL, Germonpré MB, Sablin MV, López-Giráldez F, Domingo-Roura X, Napierala H, Uerpmann HP, Loponte DM, Acosta AA, Giemsch L, Schmitz RW, Worthington B, Buikstra JE, Druzhkova A, Graphodatsky AS, Ovodov ND, Wahlberg N, Freedman AH, Schweizer RM, Koepfli KP, Leonard JA, Meyer M, Krause J, Pääbo S, Green RE, Wayne RK. Complete mitochondrial genomes of ancient canids suggest a European origin of domestic dogs. Science. 2013;342:871–4.CrossRefGoogle Scholar
  65. Toro R, Pérez-Serra A, Campuzano O, Moncayo-Arlandi J, Allegue C, Iglesias A, Mangas A, Brugada R. Familial dilated cardiomyopathy caused by a novel frameshift in the BAG3 gene. PLoS One. 2016;11:e0158730.CrossRefGoogle Scholar
  66. Truvé K, Dickinson P, Xiong A, York D, Jayashankar K, Pielberg G, Koltookian M, Murén E, Fuxelius HH, Weishaupt H, Swartling FJ, Andersson G, Hedhammar Å, Bongcam-Rudloff E, Forsberg-Nilsson K, Bannasch D, Lindblad-Toh K. Utilizing the dog genome in the search for novel candidate genes involved in glioma development-genome wide association mapping followed by targeted massive parallel sequencing identifies a strongly associated locus. PLoS Genet. 2016;12:e1006000.CrossRefGoogle Scholar
  67. Tsai KL, Starr-Moss AN, Venkataraman GM, Robinson C, Kennedy LJ, Steiner JM, Clark LA. Alleles of the major histocompatibility complex play a role in the pathogenesis of pancreatic acinar atrophy in dogs. Immunogenetics. 2013;65:501–9.CrossRefGoogle Scholar
  68. Vaysse A, Ratnakumar A, Derrien T, Axelsson E, Rosengren Pielberg G, Sigurdsson S, Fall T, Seppälä EH, Hansen MS, Lawley CT, Karlsson EK, Consortium LUPA, Bannasch D, Vilà C, Lohi H, Galibert F, Fredholm M, Häggström J, Hedhammar A, André C, Lindblad-Toh K, Hitte C, Webster MT. Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping. PLoS Genet. 2011;7:e1002316.CrossRefGoogle Scholar
  69. Vonholdt BM, Pollinger JP, Lohmueller KE, Han E, Parker HG, Quignon P, Degenhardt JD, Boyko AR, Earl DA, Auton A, Reynolds A, Bryc K, Brisbin A, Knowles JC, Mosher DS, Spady TC, Elkahloun A, Geffen E, Pilot M, Jedrzejewski W, Greco C, Randi E, Bannasch D, Wilton A, Shearman J, Musiani M, Cargill M, Jones PG, Qian Z, Huang W, Ding ZL, Zhang YP, Bustamante CD, Ostrander EA, Novembre J, Wayne RK. Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication. Nature. 2010;464:898–902.CrossRefGoogle Scholar
  70. Voorbij AM, van Steenbeek FG, Vos-Loohuis M, Martens EE, Hanson-Nilsson JM, van Oost BA, Kooistra HS, Leegwater PA. A contracted DNA repeat in LHX3 intron 5 is associated with aberrant splicing and pituitary dwarfism in German Shepherd dogs. PLoS One. 2011;6:e27940.CrossRefGoogle Scholar
  71. Wang GD, Zhai W, Yang HC, Fan RX, Cao X, Zhong L, Wang L, Liu F, Wu H, Cheng LG, Poyarkov AD, Poyarkov NA Jr, Tang SS, Zhao WM, Gao Y, Lv XM, Irwin DM, Savolainen P, Wu CI, Zhang YP. The genomics of selection in dogs and the parallel evolution between dogs and humans. Nat Commun. 2013;4:1860.CrossRefGoogle Scholar
  72. Wiik AC, Ropstad EO, Ekesten B, Karlstam L, Wade CM, Lingaas F. Progressive retinal atrophy in Shetland sheepdog is associated with a mutation in the CNGA1 gene. Anim Genet. 2015;46:515–21.CrossRefGoogle Scholar
  73. Wijesena HR, Schmutz SM. A missense mutation in SLC45A2 is associated with albinism in several small long haired dog breeds. J Hered. 2015;106:285–8.CrossRefGoogle Scholar
  74. Winkler PA, Gornik KR, Ramsey DT, Dubielzig RR, Venta PJ, Petersen-Jones SM, Bartoe JT. A partial gene deletion of SLC45A2 causes oculocutaneous albinism in Doberman pinscher dogs. PLoS One. 2014;9:e92127.CrossRefGoogle Scholar
  75. Wolf ZT, Brand HA, Shaffer JR, Leslie EJ, Arzi B, Willet CE, Cox TC, McHenry T, Narayan N, Feingold E, Wang X, Sliskovic S, Karmi N, Safra N, Sanchez C, Deleyiannis FW, Murray JC, Wade CM, Marazita ML, Bannasch DL. Genome-wide association studies in dogs and humans identify ADAMTS20 as a risk variant for cleft lip and palate. PLoS Genet. 2015;11:e1005059.CrossRefGoogle Scholar
  76. Wong AK, Ruhe AL, Robertson KR, Loew ER, Williams DC, Neff MW. A de novo mutation in KIT causes white spotting in a subpopulation of German Shepherd dogs. Anim Genet. 2013;44:305–10.CrossRefGoogle Scholar
  77. Yang M, Geng GJ, Zhang W, Cui L, Zhang HX, Zheng JL. SNP genotypes of olfactory receptor genes associated with olfactory ability in German Shepherd dogs. Anim Genet. 2016;47:240–4.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Kristopher J. L. Irizarry
    • 1
    Email author
  • Elton J. R. Vasconcelos
    • 1
  1. 1.The Applied Genomics Center, College of Veterinary MedicineWestern University of Health SciencesPomonaUSA

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