1932

Abstract

Advances in DNA sequencing and other technologies have greatly facilitated the identification of genetic risk factors for inherited diseases in dogs. We review recent technological developments based on selected examples from canine disease genetics. The identification of disease-causing variants in dogs with monogenic diseases may become a widely employed diagnostic approach in clinical veterinary medicine in the not-too-distant future. Diseases with complex modes of inheritance continue to pose challenges to researchers but have also become much more tangible than in the past. In addition to strategies for identifying genetic risk factors, we provide some thoughts on the interpretation of sequence variants that are largely inspired by developments in human clinical genetics.

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2023-02-15
2024-05-09
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Literature Cited

  1. 1.
    Shearin AL, Ostrander EA. 2010. Leading the way: canine models of genomics and disease. DMM Dis. Models Mech. 3:1–22734
    [Google Scholar]
  2. 2.
    Khanna C, Lindblad-Toh K, Vail D, London C, Bergman P et al. 2006. The dog as a cancer model. Nat. Biotechnol. 24:9106566
    [Google Scholar]
  3. 3.
    Pinho SS, Carvalho S, Cabral J, Reis CA, Gärtner F. 2012. Canine tumors: a spontaneous animal model of human carcinogenesis. Transl. Res. 159:316572
    [Google Scholar]
  4. 4.
    Gardner HL, Fenger JM, London CA. 2016. Dogs as a model for cancer. Annu. Rev. Anim. Biosci. 4:199222
    [Google Scholar]
  5. 5.
    Hakim CH, Kumar SRP, Pérez-López DO, Wasala NB, Zhang D et al. 2021. Cas9-specific immune responses compromise local and systemic AAV CRISPR therapy in multiple dystrophic canine models. Nat. Commun. 12:16769
    [Google Scholar]
  6. 6.
    Marcó S, Haurigot V, Jaén ML, Ribera A, Sánchez V et al. 2021. Seven-year follow-up of durability and safety of AAV CNS gene therapy for a lysosomal storage disorder in a large animal. Mol. Ther. Methods Clin. Dev. 23:37089
    [Google Scholar]
  7. 7.
    Aguirre GD, Cideciyan AV, Dufour VL, Ripolles-García A, Sudharsan R et al. 2021. Gene therapy reforms photoreceptor structure and restores vision in NPHP5-associated Leber congenital amaurosis. Mol. Ther. 29:8245668
    [Google Scholar]
  8. 8.
    Creevy KE, Akey JM, Kaeberlein M, Promislow DEL, Barnett BG et al. 2022. An open science study of ageing in companion dogs. Nature 602:78955157
    [Google Scholar]
  9. 9.
    Zangerl B, Goldstein O, Philp AR, Lindauer SJP, Pearce-Kelling SE et al. 2006. Identical mutation in a novel retinal gene causes progressive rod-cone degeneration in dogs and retinitis pigmentosa in humans. Genomics 88:555163
    [Google Scholar]
  10. 10.
    Drögemüller M, Jagannathan V, Becker D, Drögemüller C, Schelling C et al. 2014. A mutation in the FAM83G gene in dogs with hereditary footpad hyperkeratosis (HFH). PLOS Genet. 10:5e1004370
    [Google Scholar]
  11. 11.
    Drögemüller C, Becker D, Brunner A, Haase B, Kircher P et al. 2009. A missense mutation in the SERPINH1 gene in Dachshunds with osteogenesis imperfecta. PLOS Genet. 5:7e1000579
    [Google Scholar]
  12. 12.
    Grall A, Guaguère E, Planchais S, Grond S, Bourrat E et al. 2012. PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans. Nat. Genet. 44:214047
    [Google Scholar]
  13. 13.
    Vernau KM, Runstadler JA, Brown EA, Cameron JM, Huson HJ et al. 2013. Genome-wide association analysis identifies a mutation in the thiamine transporter 2 (SLC19A3) gene associated with Alaskan Husky encephalopathy. PLOS ONE 8:3e57195
    [Google Scholar]
  14. 14.
    Mansour TA, Lucot K, Konopelski SE, Dickinson PJ, Sturges BK et al. 2018. Whole genome variant association across 100 dogs identifies a frame shift mutation in DISHEVELLED 2 which contributes to Robinow-like syndrome in Bulldogs and related screw tail dog breeds. PLOS Genet. 14:12e1007850
    [Google Scholar]
  15. 15.
    Bauer A, Waluk DP, Galichet A, Timm K, Jagannathan V et al. 2017. A de novo variant in the ASPRV1 gene in a dog with ichthyosis. PLOS Genet. 13:3e1006651
    [Google Scholar]
  16. 16.
    Karlsson EK, Lindblad-Toh K. 2008. Leader of the pack: gene mapping in dogs and other model organisms. Nat. Rev. Genet. 9:971325
    [Google Scholar]
  17. 17.
    Dreger DL, Rimbault M, Davis BW, Bhatnagar A, Parker HG, Ostrander EA. 2016. Whole-genome sequence, SNP chips and pedigree structure: building demographic profiles in domestic dog breeds to optimize genetic-trait mapping. Dis. Model Mech. 9:12144560
    [Google Scholar]
  18. 18.
    Auton A, Abecasis GR, Altshuler DM, Durbin RM, Bentley DR et al. 2015. A global reference for human genetic variation. Nature 526:75716874
    [Google Scholar]
  19. 19.
    Ali MB, Evans JM, Parker HG, Kim J, Pearce-Kelling S et al. 2020. Genetic analysis of the modern Australian labradoodle dog breed reveals an excess of the poodle genome. PLOS Genet. 16:9e1008956
    [Google Scholar]
  20. 20.
    Bannasch D, Famula T, Donner J, Anderson H, Honkanen L et al. 2021. The effect of inbreeding, body size and morphology on health in dog breeds. Canine Med. Genet. 8:12
    [Google Scholar]
  21. 21.
    Lepori V, Mühlhause F, Sewell AC, Jagannathan V, Janzen N et al. 2018. A nonsense variant in the ACADVL gene in German Hunting Terriers with exercise induced metabolic myopathy. G3 8:5154554
    [Google Scholar]
  22. 22.
    Has C, Bauer JW, Bodemer C, Bolling MC, Bruckner-Tuderman L et al. 2020. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br. J. Dermatol. 183:461427
    [Google Scholar]
  23. 23.
    Garcia TM, Kiener S, Jagannathan V, Russell DS, Leeb T. 2020. A COL7A1 variant in a litter of neonatal Basset Hounds with dystrophic epidermolysis bullosa. Genes 11:121458
    [Google Scholar]
  24. 24.
    Candille SI, Kaelin CB, Cattanach BM, Yu B, Thompson DA et al. 2007. A β-defensin mutation causes black coat color in domestic dogs. Science 318:5855141823
    [Google Scholar]
  25. 25.
    Parker HG, VonHoldt BM, Quignon P, Margulies EH, Shao S et al. 2009. An expressed Fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. Science 325:594399598
    [Google Scholar]
  26. 26.
    Brown EA, Dickinson PJ, Mansour T, Sturges BK, Aguilar M et al. 2017. FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs. PNAS 114:431147681
    [Google Scholar]
  27. 27.
    Karlsson EK, Baranowska I, Wade CM, Salmon Hillbertz NHC, Zody MC et al. 2007. Efficient mapping of Mendelian traits in dogs through genome-wide association. Nat. Genet. 39:11132128
    [Google Scholar]
  28. 28.
    Uffelmann E, Huang QQ, Munung NS, de Vries J, Okada Y et al. 2021. Genome-wide association studies. Nat. Rev. Methods Primers 1:59
    [Google Scholar]
  29. 29.
    Vaysse A, Ratnakumar A, Derrien T, Axelsson E, Pielberg GR et al. 2011. Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping. PLOS Genet. 7:10e1002316
    [Google Scholar]
  30. 30.
    Boyko AR, Quignon P, Li L, Schoenebeck JJ, Degenhardt JD et al. 2010. A simple genetic architecture underlies morphological variation in dogs. PLOS Biol. 8:84950
    [Google Scholar]
  31. 31.
    Bannasch D, Young A, Myers J, Truvé K, Dickinson P et al. 2010. Localization of canine brachycephaly using an across breed mapping approach. PLOS ONE 5:3e9632
    [Google Scholar]
  32. 32.
    Marchant TW, Johnson EJ, McTeir L, Johnson CI, Gow A et al. 2017. Canine brachycephaly is associated with a retrotransposon-mediated missplicing of SMOC2. Curr. Biol. 27:11157384.e6
    [Google Scholar]
  33. 33.
    Anderson H, Honkanen L, Ruotanen P, Mathlin J, Donner J. 2020. Comprehensive genetic testing combined with citizen science reveals a recently characterized ancient MC1R mutation associated with partial recessive red phenotypes in dog. Canine Med. Genet. 7:16
    [Google Scholar]
  34. 34.
    Cadieu E, Neff MW, Quignon P, Walsh K, Chase K et al. 2009. Coat variation in the domestic dog is governed by variants in three genes. Science 326:594915053
    [Google Scholar]
  35. 35.
    Plassais J, Kim J, Davis BW, Karyadi DM, Hogan AN et al. 2019. Whole genome sequencing of canids reveals genomic regions under selection and variants influencing morphology. Nat. Commun. 10:1489
    [Google Scholar]
  36. 36.
    Kyöstilä K, Syrjä P, Jagannathan V, Chandrasekar G, Jokinen TS et al. 2015. A missense change in the ATG4D gene links aberrant autophagy to a neurodegenerative vacuolar storage disease. PLOS Genet. 11:4e1005169
    [Google Scholar]
  37. 37.
    Lander ES, Botstein D. 1987. Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. Science 236:4808156770
    [Google Scholar]
  38. 38.
    Marchant TW, Dietschi E, Rytz U, Schawalder P, Jagannathan V et al. 2019. An ADAMTS3 missense variant is associated with Norwich Terrier upper airway syndrome. PLOS Genet. 15:5e1008102
    [Google Scholar]
  39. 39.
    Drögemüller C, Karlsson EK, Hytönen MK, Perloski M, Dolf G et al. 2008. A mutation in hairless dogs implicates FOXI3 in ectodermal development. Science 321:58951462
    [Google Scholar]
  40. 40.
    Backel KA, Kiener S, Jagannathan V, Casal ML, Leeb T, Mauldin EA. 2020. A DSG1 frameshift variant in a Rottweiler dog with footpad hyperkeratosis. Genes 11:4469
    [Google Scholar]
  41. 41.
    Jagannathan V, Drögemüller C, Leeb T, Aguirre G, André C et al. 2019. A comprehensive biomedical variant catalogue based on whole genome sequences of 582 dogs and eight wolves. Anim. Genet. 50:6695704
    [Google Scholar]
  42. 42.
    Besenbacher S, Liu S, Izarzugaza JMG, Grove J, Belling K et al. 2015. Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios. Nat. Commun. 6:5969
    [Google Scholar]
  43. 43.
    Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P et al. 2012. Rate of de novo mutations and the importance of father's age to disease risk. Nature 488:741247175
    [Google Scholar]
  44. 44.
    Harland C, Charlier C, Karim L, Cambisano N, Deckers M et al. 2017. Frequency of mosaicism points towards mutation-prone early cleavage cell divisions in cattle. bioRxiv 079863. https://doi.org/10.1101/079863
    [Crossref]
  45. 45.
    Wang J, Kong L, Gao G, Luo J. 2013. A brief introduction to web-based genome browsers. Brief. Bioinform. 14:213143
    [Google Scholar]
  46. 46.
    Cheng H, Concepcion GT, Feng X, Zhang H, Li H. 2021. Haplotype-resolved de novo assembly using phased assembly graphs with hifiasm. Nat. Methods 18:217075
    [Google Scholar]
  47. 47.
    Lindblad-Toh K, Wade Claire M, Mikkelsen TS, Karlsson EK, Jaffe DB et al. 2005. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 438:706980319
    [Google Scholar]
  48. 48.
    Jagannathan V, Hitte C, Kidd JM, Masterson P, Murphy TD et al. 2021. Dog10K_Boxer_Tasha_1.0: a long-read assembly of the dog reference genome. Genes 12:6847
    [Google Scholar]
  49. 49.
    Edwards RJ, Field MA, Ferguson JM, Dudchenko O, Keilwagen J et al. 2021. Chromosome-length genome assembly and structural variations of the primal Basenji dog (Canis lupus familiaris) genome. BMC Genom. 22:188
    [Google Scholar]
  50. 50.
    Field MA, Rosen BD, Dudchenko O, Chan EKF, Minoche AE et al. 2020. Canfam_GSD: de novo chromosome-length genome assembly of the German Shepherd Dog (Canis lupus familiaris) using a combination of long reads, optical mapping, and Hi-C. GigaScience 9:4giaa027
    [Google Scholar]
  51. 51.
    Wang C, Wallerman O, Arendt M-L, Sundström E, Karlsson Å et al. 2021. A novel canine reference genome resolves genomic architecture and uncovers transcript complexity. Commun. Biol. 4:185
    [Google Scholar]
  52. 52.
    Halo JV, Pendleton AL, Shen F, Doucet AJ, Derrien T et al. 2021. Long-read assembly of a Great Dane genome highlights the contribution of GC-rich sequence and mobile elements to canine genomes. PNAS 118:11e2016274118
    [Google Scholar]
  53. 53.
    Sinding M-HS, Gopalakrishnan S, Raundrup K, Dalén L, Threlfall J, Gilbert T. 2021. The genome sequence of the grey wolf, Canis lupus Linnaeus 1758. Wellcome Open Res. 6:310
    [Google Scholar]
  54. 54.
    Field MA, Yadav S, Dudchenko O, Esvaran M, Rosen BD et al. 2022. The Australian dingo is an early offshoot of modern breed dogs. Sci. Adv. 8:16eabm5944
    [Google Scholar]
  55. 55.
    Natl. Cent. Biotechnol. Inf. (NCBI) 2020. Canis lupus familiaris annotation release 106 Annot. Rep. NCBI Bethesda, MD: https://www.ncbi.nlm.nih.gov/genome/annotation_euk/Canis_lupus_familiaris/106/accessed06-May-2022
  56. 56.
    Wucher V, Legeai F, Hédan B, Rizk G, Lagoutte L et al. 2017. FEELnc: a tool for long non-coding RNA annotation and its application to the dog transcriptome. Nucleic Acids Res. 45:8e57
    [Google Scholar]
  57. 57.
    Yamazaki J, Matsumoto Y, Jelinek J, Ishizaki T, Maeda S et al. 2021. DNA methylation landscape of 16 canine somatic tissues by methylation-sensitive restriction enzyme-based next generation sequencing. Sci. Rep. 11:10005
    [Google Scholar]
  58. 58.
    Megquier K, Genereux DP, Hekman J, Swofford R, Turner-Maier J et al. 2019. BarkBase: epigenomic annotation of canine genomes. Genes 10:433
    [Google Scholar]
  59. 59.
    Ballester B, Medina-Rivera A, Schmidt D, González-Porta M, Carlucci M et al. 2014. Multi-species, multi-transcription factor binding highlights conserved control of tissue-specific biological pathways. eLife 3:e02626
    [Google Scholar]
  60. 60.
    Schmidt D, Wilson MD, Ballester B, Schwalie PC, Brown GD et al. 2010. Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding. Science 328:103640
    [Google Scholar]
  61. 61.
    Genereux DP, Serres A, Armstrong J, Johnson J, Marinescu VD et al. 2020. A comparative genomics multitool for scientific discovery and conservation. Nature 587:24045
    [Google Scholar]
  62. 62.
    Zhang W, Eory L, Salavati M, Clark E, Smith J et al. 2022. Applications of single-molecule real-time isoform sequencing (Iso-Seq) for unravellign complexity of dog transcriptomes. Proceedings of the 12th World Congress of Genetics Applied to Livestock Production Edinburgh: Roslin Inst In press
    [Google Scholar]
  63. 63.
    Bannasch DL, Kaelin CB, Letko A, Loechel R, Hug P et al. 2021. Dog colour patterns explained by modular promoters of ancient canid origin. Nat. Ecol. Evol. 5:10141523
    [Google Scholar]
  64. 64.
    Karyadi DM, Karlins E, Decker B, vonHoldt BM, Carpintero-Ramirez G et al. 2013. A copy number variant at the KITLG locus likely confers risk for canine squamous cell carcinoma of the digit. PLOS Genet. 9:3e1003409
    [Google Scholar]
  65. 65.
    Park K, Kang J, Subedi KP, Ha JH, Park C. 2008. Canine polydactyl mutations with heterogeneous origin in the conserved intronic sequence of LMBR1. Genetics 179:4216372
    [Google Scholar]
  66. 66.
    Olsson M, Meadows JRS, Truvé K, Pielberg GR, Puppo F et al. 2011. A novel unstable duplication upstream of HAS2 predisposes to a breed-defining skin phenotype and a periodic fever syndrome in Chinese Shar-Pei dogs. PLOS Genet. 7:3e1001332
    [Google Scholar]
  67. 67.
    Ellingford JM, Ahn JW, Bagnall RD, Baralle D, Barton S et al. 2022. Recommendations for clinical interpretation of variants found in non-coding regions of the genome. Genome Med. 14:173
    [Google Scholar]
  68. 68.
    Church DM, Schneider VA, Steinberg KM, Schatz MC, Quinlan AR et al. 2015. Extending reference assembly models. Genome Biol. 16:13
    [Google Scholar]
  69. 69.
    Sherman RM, Forman J, Antonescu V, Puiu D, Daya M et al. 2019. Assembly of a pan-genome from deep sequencing of 910 humans of African descent. Nat. Genet. 51:13035
    [Google Scholar]
  70. 70.
    Talenti A, Powell J, Hemmink JD, Cook EAJ, Wragg D et al. 2022. A cattle graph genome incorporating global breed diversity. Nat. Commun. 13:910
    [Google Scholar]
  71. 71.
    Crysnanto D, Leonard AS, Fang ZH, Pausch H. 2021. Novel functional sequences uncovered through a bovine multiassembly graph. PNAS 118:20e2101056118
    [Google Scholar]
  72. 72.
    Crysnanto D, Pausch H. 2020. Bovine breed-specific augmented reference graphs facilitate accurate sequence read mapping and unbiased variant discovery. Genome Biol. 21:184
    [Google Scholar]
  73. 73.
    Alkan C, Coe BP, Eichler EE. 2011. Genome structural variation discovery and genotyping. Nat. Rev. Genet. 12:536376
    [Google Scholar]
  74. 74.
    Ho SS, Urban AE, Mills RE. 2020. Structural variation in the sequencing era. Nat. Rev. Genet. 21:317189
    [Google Scholar]
  75. 75.
    Wang W, Kirkness EF. 2005. Short interspersed elements (SINEs) are a major source of canine genomic diversity. Genome Res. 15:121798808
    [Google Scholar]
  76. 76.
    Linek M, Doelle M, Leeb T, Bauer A, Leuthard F et al. 2020. ATP2A2 SINE insertion in an Irish Terrier with Darier disease and associated infundibular cyst formation. Genes 11:5481
    [Google Scholar]
  77. 77.
    Mauri N, Kleiter M, Dietschi E, Leschnik M, Högler S et al. 2017. A SINE insertion in ATP1B2 in Belgian Shepherd dogs affected by spongy degeneration with cerebellar ataxia (SDCA2). G3 7:8272937
    [Google Scholar]
  78. 78.
    Kehl A, Haaland AH, Langbein-Detsch I, Mueller E. 2021. A sine insertion in F8 gene leads to severe form of hemophilia A in a family of Rhodesian Ridgebacks. Genes 12:2134
    [Google Scholar]
  79. 79.
    Pelé M, Tiret L, Kessler JL, Blot S, Panthier JJ. 2005. SINE exonic insertion in the PTPLA gene leads to multiple splicing defects and segregates with the autosomal recessive centronuclear myopathy in dogs. Hum. Mol. Genet. 14:11141727
    [Google Scholar]
  80. 80.
    Wiedmer M, Oevermann A, Borer-Germann SE, Gorgas D, Shelton GD et al. 2016. A RAB3GAP1 SINE insertion in Alaskan Huskies with polyneuropathy, ocular abnormalities, and neuronal vacuolation (POANV) resembling human Warburg micro syndrome 1 (WARBM1). G3 6:225562
    [Google Scholar]
  81. 81.
    Downs LM, Mellersh CS. 2014. An intronic SINE insertion in FAM161A that causes exon-skipping is associated with progressive retinal atrophy in Tibetan Spaniels and Tibetan Terriers. PLOS ONE 9:4e93990
    [Google Scholar]
  82. 82.
    Clark LA, Wahl JM, Rees CA, Murphy KE. 2006. Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog. PNAS 103:5137681
    [Google Scholar]
  83. 83.
    Wolf ZT, Leslie EJ, Arzi B, Jayashankar K, Karmi N et al. 2014. A LINE-1 insertion in DLX6 is responsible for cleft palate and mandibular abnormalities in a canine model of Pierre Robin sequence. PLOS Genet. 10:4e1004257
    [Google Scholar]
  84. 84.
    Credille KM, Minor JS, Barnhart KF, Lee E, Cox ML et al. 2009. Transglutaminase 1-deficient recessive lamellar ichthyosis associated with a LINE-1 insertion in Jack Russell terrier dogs. Br. J. Dermatol. 161:226572
    [Google Scholar]
  85. 85.
    Batcher K, Dickinson P, Maciejczyk K, Brzeski K, Rasouliha SH et al. 2020. Multiple FGF4 retrocopies recently derived within canids. Genes 11:8839
    [Google Scholar]
  86. 86.
    Leuthard F, Lehner G, Jagannathan V, Leeb T, Welle M. 2019. A missense variant in the NSDHL gene in a Chihuahua with a congenital cornification disorder resembling inflammatory linear verrucous epidermal nevi. Anim. Genet. 50:676871
    [Google Scholar]
  87. 87.
    Christen M, Austel M, Banovic F, Jagannathan V, Leeb T. 2020. NSDHL frameshift deletion in a mixed breed dog with progressive epidermal nevi. Genes 11:111297
    [Google Scholar]
  88. 88.
    Megquier K, Turner-Maier J, Swofford R, Kim JH, Sarver AL et al. 2019. Comparative genomics reveals shared mutational landscape in canine hemangiosarcoma and human angiosarcoma. Mol. Cancer Res. 17:12241021
    [Google Scholar]
  89. 89.
    Dillard KJ, Ochs M, Niskanen JE, Arumilli M, Donner J et al. 2020. Recessive missense LAMP3 variant associated with defect in lamellar body biogenesis and fatal neonatal interstitial lung disease in dogs. PLOS Genet. 16:3e1008651
    [Google Scholar]
  90. 90.
    Koboldt DC. 2020. Best practices for variant calling in clinical sequencing. Genome Med. 12:91
    [Google Scholar]
  91. 91.
    Robinson JT, Thorvaldsdóttir H, Winckler W, Guttman M, Lander ES et al. 2011. Integrative genomics viewer. Nat. Biotechnol. 29:12426
    [Google Scholar]
  92. 92.
    Robinson JT, Thorvaldsdóttir H, Wenger AM, Zehir A, Mesirov JP. 2017. Variant review with the integrative genomics viewer. Cancer Res. 77:21e3134
    [Google Scholar]
  93. 93.
    Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J et al. 2020. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581:780943443
    [Google Scholar]
  94. 94.
    Giani AM, Gallo GR, Gianfranceschi L, Formenti G. 2019. Long walk to genomics: history and current approaches to genome sequencing and assembly. Comput. Struct. Biotechnol. J. 18:919
    [Google Scholar]
  95. 95.
    Nicholas FW. 1998. Genetic databases: online catalogues of inherited disorders. OIE Rev. Sci. Tech. 17:134650
    [Google Scholar]
  96. 96.
    Nicholas FW. 2021. Online Mendelian Inheritance in Animals (OMIA): a record of advances in animal genetics, freely available on the Internet for 25 years. Anim. Genet. 52:139
    [Google Scholar]
  97. 97.
    Shelton GD, Podell M, Poncelet L, Schatzberg S, Patterson E et al. 2003. Inherited polyneuropathy in Leonberger dogs: A mixed or intermediate form of Charcot-Marie-Tooth disease?. Muscle Nerve 27:447177
    [Google Scholar]
  98. 98.
    Hultin Jäderlund K, Baranowska Körberg I, Nødtvedt A 2011. Inherited polyneuropathy in Leonberger dogs. J. Vet. Intern. Med. 25:59971002
    [Google Scholar]
  99. 99.
    Becker D, Minor KM, Letko A, Ekenstedt KJ, Jagannathan V et al. 2017. A GJA9 frameshift variant is associated with polyneuropathy in Leonberger dogs. BMC Genom. 18:662
    [Google Scholar]
  100. 100.
    Letko A, Minor KM, Friedenberg SG, Shelton GD, Salvador JP et al. 2020. A CNTNAP1 missense variant is associated with canine laryngeal paralysis and polyneuropathy. Genes 11:121426
    [Google Scholar]
  101. 101.
    Ekenstedt KJ, Becker D, Minor KM, Shelton GD, Patterson EE et al. 2014. An ARHGEF10 deletion is highly associated with a juvenile-onset inherited polyneuropathy in Leonberger and Saint Bernard dogs. PLOS Genet. 10:10e1004635
    [Google Scholar]
  102. 102.
    Mauri N, Kleiter M, Leschnik M, Högler S, Dietschi E et al. 2017. A missense variant in KCNJ10 in Belgian Shepherd dogs affected by spongy degeneration with cerebellar ataxia (SDCA1). G3 7:266369
    [Google Scholar]
  103. 103.
    Gurtner C, Hug P, Kleiter M, Köhler K, Dietschi E et al. 2020. YARS2 missense variant in Belgian Shepherd dogs with cardiomyopathy and juvenile mortality. Genes 11:3313
    [Google Scholar]
  104. 104.
    Christen M, Högler S, Kleiter M, Leschnik M, Weber C et al. 2021. Deletion of the SELENOP gene leads to CNS atrophy with cerebellar ataxia in dogs. PLOS Genet. 17:8e1009716
    [Google Scholar]
  105. 105.
    Parshall CJ, Wyman M, Nitroy S, Acland GM, Aguirre GD. 1991. Photoreceptor dysplasia: an inherited progressive retinal atrophy of Miniature Schnauzer dogs. Prog. Vet. Comp. Ophthalmol. 1:3187203
    [Google Scholar]
  106. 106.
    Murgiano L, Becker D, Torjman D, Niggel JK, Milano A et al. 2019. Complex structural PPT1 variant associated with non-syndromic canine retinal degeneration. G3 9:242537
    [Google Scholar]
  107. 107.
    Aguirre GD, Lohi H, Kaukonen M, Murgiano L. 2020. Formal commentary. PLOS Genet. 16:11e1009059
    [Google Scholar]
  108. 108.
    World Health Organ 2022. Global health estimates: leading causes of DALYs Doc., World Health Organ. Geneva: accessed May 6, 2022. https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates/global-health-estimates-leading-causes-of-dalys
  109. 109.
    O'Neill DG, James H, Brodbelt DC, Church DB, Pegram C. 2021. Prevalence of commonly diagnosed disorders in UK dogs under primary veterinary care: results and applications. BMC Vet. Res. 17:69
    [Google Scholar]
  110. 110.
    Tobias KM, Rohrbach BW. 2003. Association of breed with the diagnosis of congenital portosystemic shunts in dogs: 2,400 cases (1980–2002). J. Am. Vet. Med. Assoc. 223:11163639
    [Google Scholar]
  111. 111.
    Hayward JJ, Castelhano MG, Oliveira KC, Corey E, Balkman C et al. 2016. Complex disease and phenotype mapping in the domestic dog. Nat. Commun. 7:10460
    [Google Scholar]
  112. 112.
    Coopman F, Verhoeven G, Saunders J, Duchateau L, van Bree H. 2008. Prevalence of hip dysplasia, elbow dysplasia and humeral head osteochondrosis in dog breeds in Belgium. Vet. Rec. 163:2265458
    [Google Scholar]
  113. 113.
    Schnelle GB. 1937. Bilateral congenital subluxation of the coxo-femoral joints in a dog. Univ. Pa. Bull. Sch. Vet. Med. Vet. Ext. Q. 37:1516
    [Google Scholar]
  114. 114.
    Sánchez-Molano E, Woolliams JA, Pong-Wong R, Clements DN, Blott SC, Wiener P 2014. Quantitative trait loci mapping for canine hip dysplasia and its related traits in UK Labrador Retrievers. BMC Genom. 15:833
    [Google Scholar]
  115. 115.
    Zhou Z, Sheng X, Zhang Z, Zhao K, Zhu L et al. 2010. Differential genetic regulation of canine hip dysplasia and osteoarthritis. PLOS ONE 5:10e13219
    [Google Scholar]
  116. 116.
    Wang S, Strandberg E, Arvelius P, Clements DN, Wiener P, Friedrich J. 2021. Genome-wide association studies for canine hip dysplasia in single and multiple populations—implications and potential novel risk loci. BMC Genom. 22:636
    [Google Scholar]
  117. 117.
    Pfahler S, Distl O. 2012. Identification of quantitative trait loci (QTL) for canine hip dysplasia and canine elbow dysplasia in Bernese mountain dogs. PLOS ONE 7:11e49782
    [Google Scholar]
  118. 118.
    Fels L, Marschall Y, Philipp U, Distl O. 2014. Multiple loci associated with canine hip dysplasia (CHD) in German shepherd dogs. Mamm. Genome 25:5–626269
    [Google Scholar]
  119. 119.
    Mikkola L, Kyöstilä K, Donner J, Lappalainen AK, Hytönen MK et al. 2021. An across-breed validation study of 46 genetic markers in canine hip dysplasia. BMC Genom. 22:68
    [Google Scholar]
  120. 120.
    Friedenberg SG, Zhu L, Zhang Z, van den Foels WB, Schweitzer PA et al. 2011. Evaluation of a fibrillin 2 gene haplotype associated with hip dysplasia and incipient osteoarthritis in dogs. Am. J. Vet. Res. 72:453040
    [Google Scholar]
  121. 121.
    Fels L, Distl O. 2014. Identification and validation of quantitative trait loci (QTL) for canine hip dysplasia (CHD) in German Shepherd dogs. PLOS ONE 9:5e96618
    [Google Scholar]
  122. 122.
    Lavrijsen ICM, Leegwater PAJ, Martin AJ, Harris SJ, Tryfonidou MA et al. 2014. Genome wide analysis indicates genes for basement membrane and cartilage matrix proteins as candidates for hip dysplasia in Labrador Retrievers. PLOS ONE 9:1e87735
    [Google Scholar]
  123. 123.
    Niskanen JE, Reunanen V, Salonen M, Bannasch D, Lappalainen AK et al. 2021. Canine DVL2 variant contributes to brachycephalic phenotype and caudal vertebral anomalies. Hum. Genet. 140:11153545
    [Google Scholar]
  124. 124.
    O'Neill DG, Lee MM, Brodbelt DC, Church DB, Sanchez RF. 2017. Corneal ulcerative disease in dogs under primary veterinary care in England: epidemiology and clinical management. Canine Genet. Epidemiol. 4:5
    [Google Scholar]
  125. 125.
    Harvey CE. 1989. Inherited and congenital airway conditions. J. Small Anim. Pract. 30:318487
    [Google Scholar]
  126. 126.
    Schoenebeck JJ, Hutchinson SA, Byers A, Beale HC, Carrington B et al. 2012. Variation of BMP3 contributes to dog breed skull diversity. PLOS Genet. 8:8e1002849
    [Google Scholar]
  127. 127.
    Takahata Y, Hagino H, Kimura A, Urushizaki M, Kobayashi S et al. 2021. Smoc1 and Smoc2 regulate bone formation as downstream molecules of Runx2. Commun Biol. 4:1199
    [Google Scholar]
  128. 128.
    Alfawaz S, Fong F, Plagnol V, Wong FSL, Fearne J, Kelsell DP. 2013. Recessive oligodontia linked to a homozygous loss-of-function mutation in the SMOC2 gene. Arch. Oral Biol. 58:546266
    [Google Scholar]
  129. 129.
    Lofgren SE, Wiener P, Blott SC, Sanchez-Molano E, Woolliams JA et al. 2014. Management and personality in Labrador Retriever dogs. Appl. Anim. Behav. Sci. 156:4453
    [Google Scholar]
  130. 130.
    Chen FL, Zimmermann M, Hekman JP, Lord KA, Logan B et al. 2021. Advancing genetic selection and behavioral genomics of working dogs through collaborative science. Front. Vet. Sci. 8:662429
    [Google Scholar]
  131. 131.
    Friedrich J, Strandberg E, Arvelius P, Sánchez-Molano E, Pong-Wong R et al. 2019. Genetic dissection of complex behaviour traits in German Shepherd dogs. Heredity 123:674658
    [Google Scholar]
  132. 132.
    Guide Dogs 2022. Born to guide https://www.guidedogs.org.uk/born-to-guide
  133. 133.
    Murray JK, Kinsman RH, Lord MS, da Costa REP, Woodward JL et al. 2021.. “ Generation Pup”—protocol for a longitudinal study of dog behaviour and health. BMC Vet. Res. 17:1
    [Google Scholar]
  134. 134.
    Morrill K, Hekman J, Li X, McClure J, Logan B et al. 2022. Ancestry-inclusive dog genomics challenges popular breed stereotypes. Science 376:6592eabk0639
    [Google Scholar]
  135. 135.
    Salt C, Morris PJ, German AJ, Wilson D, Lund EM et al. 2017. Growth standard charts for monitoring bodyweight in dogs of different sizes. PLOS ONE 12:9e0182064
    [Google Scholar]
  136. 136.
    Hubrecht R, Kirkwood J, eds. 2010. The UFAW Handbook on the Care and Management of Laboratory and Other Research Animals: Eighth Edition Herts, UK: Univ. Fed. Anim. Welf.
  137. 137.
    Takahashi K, Yamanaka S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:466376
    [Google Scholar]
  138. 138.
    Kimura K, Tsukamoto M, Tanaka M, Kuwamura M, Ohtaka M et al. 2021. Efficient reprogramming of canine peripheral blood mononuclear cells into induced pluripotent stem cells. Stem Cells Dev. 30:27990
    [Google Scholar]
  139. 139.
    Yoshimatsu S, Edamura K, Yoshii Y, Iguchi A, Kondo H et al. 2021. Non-viral derivation of a transgene-free induced pluripotent stem cell line from a male beagle dog. Stem Cell Res. 53:102375
    [Google Scholar]
  140. 140.
    Yoshimatsu S, Nakajima M, Iguchi A, Sanosaka T, Sato T et al. 2021. Non-viral induction of transgene-free iPSCs from somatic fibroblasts of multiple mammalian species. Stem Cell Rep. 16:475470
    [Google Scholar]
  141. 141.
    Tobias IC, Kao MMC, Parmentier T, Hunter H, LaMarre J, Betts DH. 2020. Targeted expression profiling reveals distinct stages of early canine fibroblast reprogramming are regulated by 2-oxoglutarate hydroxylases. Stem Cell Res Ther. 11:1102375
    [Google Scholar]
  142. 142.
    Richards S, Aziz N, Bale S, Bick D, Das S et al. 2015. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17:540524
    [Google Scholar]
  143. 143.
    Freking BA, Murphy SK, Wylie AA, Rhodes SJ, Keele JW et al. 2002. Identification of the single base change causing the callipyge muscle hypertrophy phenotype, the only known example of polar overdominance in mammals. Genome Res. 12:101496506
    [Google Scholar]
  144. 144.
    Gerber M, Fischer A, Jagannathan V, Drögemüller M, Drögemüller C et al. 2015. A deletion in the VLDLR gene in Eurasier dogs with cerebellar hypoplasia resembling a Dandy-Walker-like malformation (DWLM). PLOS ONE 10:2e0108917
    [Google Scholar]
  145. 145.
    Batcher K, Varney S, York D, Blacksmith M, Kidd JM et al. 2022. Recent, full-length gene retrocopies are common in canids. Genome Res. 32:8160211
    [Google Scholar]
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