Mammalian Genome

, Volume 23, Issue 1–2, pp 40–61 | Cite as

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies

  • Keiko Miyadera
  • Gregory M. Acland
  • Gustavo D. AguirreEmail author


Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision.


Retinitis Pigmentosa Retinal Disease Positional Candidate Gene Labrador Retriever Golden Retriever 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



KM acknowledges The Kennel Club Charitable Trust (RG55218) for research funds; Fitzwilliam College, University of Cambridge, The University of Tokyo, British Council Japan Association for scholarships. Much of KM’s work is the result of the exceptional mentorship provided by Drs. David Sargan at the University of Cambridge, Cathryn Mellersh at the Animal Health Trust, Nobuo Sasaki and Kumiko Kato at The University of Tokyo, and Hiroyuki Ogawa at the Japan Animal Referral Medical Center. GMA and GDA acknowledge NEI/NIH grants EY-01244, EY06855, EY13132, and EY13729, The Foundation Fighting Blindness, The ONCE International Prize for Research & Development in Biomedicine and New Technologies for the Blind, and The Van Sloun Fund for Canine Genetic Research for their generous support. They are indebted to Sue Pearce-Kelling for her many contributions in all aspects of the research, to our scientific colleagues—research scientists, postdoctoral fellows, graduate students, and research technicians, and the staff of the RDSF—and to the dog owners for their participation in research. The authors thank Optigen LLC for disclosing unpublished data.


GMA and GDA are founding members and owners of OptiGen LLC, a company that carries out DNA testing for a large number of inherited eye diseases in dogs, and hold patents for some of these tests.

Supplementary material

335_2011_9361_MOESM1_ESM.pdf (442 kb)
Supplementary material (PDF 443 kb)


  1. Abramov I, Gordon J, Hendrickson A, Hainline L, Dobson V, LaBossiere E (1982) The retina of the newborn human infant. Science 217:265–267PubMedCrossRefGoogle Scholar
  2. Acland GM, Aguirre GD (1987) Retinal degenerations in the dog: IV. Early retinal degeneration (erd) in Norwegian elkhounds. Exp Eye Res 44:491–521PubMedCrossRefGoogle Scholar
  3. Acland GM, Aguirre GD (1995) Oculoskeletal dysplasias in Samoyed and Labrador retriever dogs: nonallelic disorders akin to Stickler-like syndromes affecting humans. In: 2nd international DOGMAP meeting, CambridgeGoogle Scholar
  4. Acland GM, Irby NL, Aguirre GD, Gross S (1984) Sudden acquired retinal degeneration in the dog: clinical and morphologic characterization of the “silent retina” syndrome. Trans Am Coll Vet Ophthalmol 15:86–104Google Scholar
  5. Acland G, Fletcher R, Gentleman S, Chader G, Aguirre G (1989) Non-allelism of three genes (rcd1, rcd2, erd) for early-onset hereditary retinal degeneration. Exp Eye Res 49:983–998PubMedCrossRefGoogle Scholar
  6. Acland GM, Blanton SH, Hershfield B, Aguirre GD (1994) XLPRA: a canine retinal degeneration inherited as an X-linked trait. Am J Med Genet 52:27–33PubMedCrossRefGoogle Scholar
  7. Acland GM, Ray K, Mellersh CS, Gu W, Langston AA, Rine J, Ostrander EA, Aguirre GD (1998) Linkage analysis and comparative mapping of canine progressive rod–cone degeneration (prcd) establishes potential locus homology with retinitis pigmentosa (RP17) in humans. Proc Natl Acad Sci USA 95:3048–3053PubMedCrossRefGoogle Scholar
  8. Acland GM, Ray K, Mellersh CS, Langston AA, Rine J, Ostrander EA, Aguirre GD (1999) A novel retinal degeneration locus identified by linkage and comparative mapping of canine early retinal degeneration. Genomics 59:134–142PubMedCrossRefGoogle Scholar
  9. Acland GM, Aguirre GD, Ray J, Zhang Q, Aleman TS, Cideciyan AV, Pearce-Kelling SE, Anand V, Zeng Y, Maguire AM, Jacobson SG, Hauswirth WW, Bennett J (2001) Gene therapy restores vision in a canine model of childhood blindness. Nat Genet 28:92–95PubMedGoogle Scholar
  10. Acland GM, Aguirre GD, Bennett J, Aleman TS, Cideciyan AV, Bennicelli J, Dejneka NS, Pearce-Kelling SE, Maguire AM, Palczewski K, Hauswirth WW, Jacobson SG (2005) Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. Mol Ther 12:1072–1082PubMedCrossRefGoogle Scholar
  11. Aguirre GD (1976) Inherited retinal degenerations in the dog. Trans Am Acad Ophthalmol Otolaryngol 81:667–676Google Scholar
  12. Aguirre G (1978) Retinal degenerations in the dog. I. Rod dysplasia. Exp Eye Res 26:233–253PubMedCrossRefGoogle Scholar
  13. Aguirre GD, Acland GM (1988) Variation in retinal degeneration phenotype inherited at the prcd locus. Exp Eye Res 46:663–687PubMedCrossRefGoogle Scholar
  14. Aguirre GD, Acland GM (2006) Models, mutants and man: searching for unique phenotypes and genes in the dog model of inherited retinal degeneration. In: Ostrander EA, Giger U, Lindblad-Toh K (eds) The dog and its genome. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 291–325Google Scholar
  15. Aguirre GD, Rubin LF (1974) Pathology of hemeralopia in the Alaskan malamute dog. Invest Ophthalmol 13:231–235PubMedGoogle Scholar
  16. Aguirre GD, Rubin LF (1975) The electroretinogram in dogs with inherited cone degeneration. Invest Ophthalmol 14:840–847PubMedGoogle Scholar
  17. Aguirre GD, Rubin LF, Bistner SI (1972) Development of the canine eye. Am J Vet Res 33:2399–2414PubMedGoogle Scholar
  18. Aguirre GD, Lolley R, Farber D, Fletcher T, Chader GJ (1978) Rod–cone dysplasia in Irish setter dogs: a defect in cyclic GMP metabolism in visual cells. Science 201:1133–1135CrossRefGoogle Scholar
  19. Aguirre G, Alligood J, O’Brien P, Buyukmihci N (1982a) Pathogenesis of progressive rod–cone degeneration in miniature poodles. Invest Ophthalmol Vis Sci 23:610–630PubMedGoogle Scholar
  20. Aguirre G, Farber D, Lolley R, O’Brien P, Alligood J, Fletcher RT, Chader G (1982b) Retinal degeneration in the dog. III. Abnormal cyclic nucleotide metabolism in rod–cone dysplasia. Exp Eye Res 35:625–642PubMedCrossRefGoogle Scholar
  21. Aguirre GD, Baldwin V, Pearce-Kelling S, Narfstrom K, Ray K, Acland GM (1998) Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect. Mol Vis 4:23–29PubMedGoogle Scholar
  22. Aguirre-Hernandez J, Sargan DR (2005) Evaluation of candidate genes in the absence of positional information: a poor bet on a blind dog! J Hered 96:475–484PubMedCrossRefGoogle Scholar
  23. Aguirre-Hernandez J, Wickstrom K, Sargan DR (2007) The Finnish lapphund retinal atrophy locus maps to the centromeric region of CFA9. BMC Vet Res 3:14PubMedCrossRefGoogle Scholar
  24. Andersson L (2009) Genome-wide association analysis in domestic animals: a powerful approach for genetic dissection of trait loci. Genetica 136:341–349PubMedCrossRefGoogle Scholar
  25. Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF, Perloski M, Biagi T, Baranowska I, Long S, March PA, Olby NJ, Shelton GD, Khan S, O’Brien DP, Lindblad-Toh K, Coates JR (2009) Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 106:2794–2799PubMedCrossRefGoogle Scholar
  26. Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, Viswanathan A, Holder GE, Stockman A, Tyler N, Petersen-Jones S, Bhattacharya SS, Thrasher AJ, Fitzke FW, Carter BJ, Rubin GS, Moore AT, Ali RR (2008) Effect of gene therapy on visual function in Leber’s congenital amaurosis. N Engl J Med 358:2231–2239PubMedCrossRefGoogle Scholar
  27. Bannasch D, Young A, Myers J, Truve K, Dickinson P, Gregg J, Davis R, Bongcam-Rudloff E, Webster MT, Lindblad-Toh K, Pedersen N (2010) Localization of canine brachycephaly using an across breed mapping approach. PLoS One 5:e9632PubMedCrossRefGoogle Scholar
  28. Barnett K (1965) Canine retinopathies–III. The other breeds. J Small Anim Pract 6:185–196CrossRefGoogle Scholar
  29. Barnett K, Stades F (1979) Collie eye anomaly in the Shetland sheepdog in the Netherlands. J Small Anim Pract 20:321–329PubMedCrossRefGoogle Scholar
  30. Barnett K, Bjorck G, Kock E (1970) Hereditary retinal dysplasia in the labrador retriever in England and in Sweden. J Small Anim Pract 10:755–759CrossRefGoogle Scholar
  31. Beltran WA, Hammond P, Acland GM, Aguirre GD (2006) A frameshift mutation in RPGR exon ORF15 causes photoreceptor degeneration and inner retina remodeling in a model of X-linked retinitis pigmentosa. Invest Ophthalmol Vis Sci 47:1669–1681PubMedCrossRefGoogle Scholar
  32. Berson E, Rosner B, Sandberg M, Dryja T (1991) Ocular findings in patients with autosomal dominant retinitis pigmentosa and a rhodopsin gene defect (PRO-23-HIS). Arch Ophthalmol 109:92–101PubMedCrossRefGoogle Scholar
  33. Booij JC, Florijn RJ, ten Brink JB, Loves W, Meire F, van Schooneveld MJ, de Jong PT, Bergen AA (2005) Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa. J Med Genet 42:e67PubMedCrossRefGoogle Scholar
  34. Bowes C, Li T, Danciger M, Baxter LC, Applebury ML, Farber DB (1990) Retinal degeneration in the rd mouse is caused by a defect in the ß subunit of rod cGMP-phosphodiesterase. Nature 347:677–680PubMedCrossRefGoogle Scholar
  35. Boyko AR, Quignon P, Li L, Schoenebeck JJ, Degenhardt JD, Lohmueller KE, Zhao K, Brisbin A, Parker HG, von Holdt BM, Cargill M, Auton A, Reynolds A, Elkahloun AG, Castelhano M, Mosher DS, Sutter NB, Johnson GS, Novembre J, Hubisz MJ, Siepel A, Wayne RK, Bustamante CD, Ostrander EA (2010) A simple genetic architecture underlies morphological variation in dogs. PLoS Biol 8:e1000451PubMedCrossRefGoogle Scholar
  36. Breen M, Jouquand S, Renier C, Mellersh CS, Hitte C, Holmes NG, Chéron A, Suter N, Vignaux F, Bristow AE, Priat C, McCann E, André C, Boundy S, Gitsham P, Thomas R, Bridge WL, Spriggs HF, Ryder EJ, Curson A, Sampson J, Ostrander EA, Binns MM, Galibert F (2001) Chromosome-specific single-locus FISH probes allow anchorage of an 1800-marker integrated radiation-hybrid/linkage map of the domestic dog genome to all chromosomes. Genome Res 11:1784–1795PubMedCrossRefGoogle Scholar
  37. Busse C, Barnett KC, Mellersh CS, Adams VJ (2011) Ophthalmic and cone derived electrodiagnostic findings in outbred miniature long-haired dachshunds homozygous for a RPGRIP1 mutation. Vet Ophthalmol 14:146–152PubMedCrossRefGoogle Scholar
  38. Cadieu E, Neff MW, Quignon P, Walsh K, Chase K, Parker HG, Vonholdt BM, Rhue A, Boyko A, Byers A, Wong A, Mosher DS, Elkahloun AG, Spady TC, Andre C, Lark KG, Cargill M, Bustamante CD, Wayne RK, Ostrander EA (2009) Coat variation in the domestic dog is governed by variants in three genes. Science 326:150–153PubMedCrossRefGoogle Scholar
  39. Carrig C, Sponenberg D, Schmidt G, Tvedten H (1988) Inheritance of associated ocular and skeletal dysplasia in Labrador retrievers. J Am Vet Med Assoc 193:1269–1272PubMedGoogle Scholar
  40. Cideciyan AV, Jacobson SG, Aleman TS, Gu D, Pearce-Kelling SE, Sumaroka A, Acland GM, Aguirre GD (2005) In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa. Proc Natl Acad Sci USA 102:5233–5238PubMedCrossRefGoogle Scholar
  41. Clements PJ, Gregory CY, Peterson-Jones SM, Sargan DR, Bhattacharya SS (1993) Confirmation of the rod cGMP phosphodiesterase ß subunit (PDEß) nonsense mutation in affected rcd-1 Irish setters in the UK and development of a diagnostic test. Curr Eye Res 12:861–866PubMedCrossRefGoogle Scholar
  42. Cullen CL, Grahn BH (2002) Diagnostic ophthalmology. Acute prechiasmal blindness due to sudden acquired retinal degeneration syndrome. Can Vet J 43:729–730PubMedGoogle Scholar
  43. Curcio CA, Sloan KR, Kalina RE, Hendrickson AE (1990) Human photoreceptor topography. J Comp Neurol 292:497–523PubMedCrossRefGoogle Scholar
  44. Curtis R, Barnett KC (1993) Progressive retinal atrophy in miniature longhaired dachshund dogs. Br Vet J 149:71–85PubMedGoogle Scholar
  45. Dekomien G, Epplen JT (2002a) The canine Phosducin gene: characterization of the exon-intron structure and exclusion as a candidate gene for generalized progressive retinal atrophy in 11 dog breeds. Mol Vis 8:138–142PubMedGoogle Scholar
  46. Dekomien G, Epplen JT (2002b) The canine recoverin (RCV1) gene: a candidate gene for generalized progressive retinal atrophy. Mol Vis 8:436–441PubMedGoogle Scholar
  47. Dekomien G, Epplen JT (2002c) Screening of the arrestin gene in dogs afflicted with generalized progressive retinal atrophy. BMC Genet 3:12PubMedCrossRefGoogle Scholar
  48. Dekomien G, Epplen JT (2003) Analysis of PDE6D and PDE6G genes for generalised progressive retinal atrophy (gPRA) mutations in dogs. Genet Sel Evol 35:445–456PubMedCrossRefGoogle Scholar
  49. Dekomien G, Runte M, Godde R, Epplen JT (2000) Generalized progressive retinal atrophy of Sloughi dogs is due to an 8-bp insertion in exon 21 of the PDE6B gene. Cytogenet Cell Genet 90:261–267PubMedCrossRefGoogle Scholar
  50. Dekomien G, Vollrath C, Petrasch-Parwez E, Boeve MH, Akkad DA, Gerding WM, Epplen JT (2010) Progressive retinal atrophy in Schapendoes dogs: mutation of the newly identified CCDC66 gene. Neurogenetics 11:163–174PubMedCrossRefGoogle Scholar
  51. Dodman NH, Karlsson EK, Moon-Fanelli A, Galdzicka M, Perloski M, Shuster L, Lindblad-Toh K, Ginns EI (2010) A canine chromosome 7 locus confers compulsive disorder susceptibility. Mol Psychiatry 15:8–10PubMedCrossRefGoogle Scholar
  52. Downs LM, Wallin-Hakansson B, Boursnell M, Marklund S, Hedhammar A, Truve K, Hubinette L, Lindblad-Toh K, Bergstrom T, Mellersh CS (2011) A frameshift mutation in Golden Retriever dogs with progressive retinal atrophy endorses SLC4A3 as a candidate gene for human retinal degenerations. PLoS One 6:e21452PubMedCrossRefGoogle Scholar
  53. Drogemuller C, Karlsson EK, Hytonen MK, Perloski M, Dolf G, Sainio K, Lohi H, Lindblad-Toh K, Leeb T (2008) A mutation in hairless dogs implicates FOXI3 in ectodermal development. Science 321:1462PubMedCrossRefGoogle Scholar
  54. Drogemuller C, Becker D, Brunner A, Haase B, Kircher P, Seeliger F, Fehr M, Baumann U, Lindblad-Toh K, Leeb T (2009) A missense mutation in the SERPINH1 gene in dachshunds with osteogenesis imperfecta. PLoS Genet 5:e1000579PubMedCrossRefGoogle Scholar
  55. Drogemuller C, Becker D, Kessler B, Kemter E, Tetens J, Jurina K, Jaderlund KH, Flagstad A, Perloski M, Lindblad-Toh K, Matiasek K (2010) A deletion in the N-myc downstream regulated gene 1 (NDRG1) gene in Greyhounds with polyneuropathy. PLoS One 5:e11258PubMedCrossRefGoogle Scholar
  56. Dryja TP, Adams SM, Grimsby JL, McGee TL, Hong DH, Li T, Andreasson S, Berson EL (2001) Null RPGRIP1 alleles in patients with Leber congenital amaurosis. Am J Hum Genet 68:1295–1298PubMedCrossRefGoogle Scholar
  57. Farber D, Lolley R (1974) Cyclic guanosine monophosphate: elevation in degenerating photoreceptor cells of the C3H mouse retina. Science 186:449–451PubMedCrossRefGoogle Scholar
  58. Farber DB, Danciger JS, Aguirre G (1992) The beta subunit of cyclic GMP phosphodiesterase mRNA is deficient in canine rod–cone dysplasia 1. Neuron 9:349–356PubMedCrossRefGoogle Scholar
  59. Farias FH, Zeng R, Johnson GS, Wininger FA, Taylor JF, Schnabel RD, McKay SD, Sanders DN, Lohi H, Seppala EH, Wade CM, Lindblad-Toh K, O’Brien DP, Katz ML (2011) A truncating mutation in ATP13A2 is responsible for adult-onset neuronal ceroid lipofuscinosis in Tibetan terriers. Neurobiol Dis 42:468–474PubMedCrossRefGoogle Scholar
  60. Farrar GJ, McWilliam P, Bradley DG, Kenna P, Lawler M, Sharp EM, Humphries MM, Eiberg H, Conneally PM, Trofatter JA et al (1990) Autosomal dominant retinitis pigmentosa: linkage to rhodopsin and evidence for genetic heterogeneity. Genomics 8:35–40PubMedCrossRefGoogle Scholar
  61. Gerber S, Perrault I, Hanein S, Barbet F, Ducroq D, Ghazi I, Martin-Coignard D, Leowski C, Homfray T, Dufier JL, Munnich A, Kaplan J, Rozet JM (2001) Complete exon-intron structure of the RPGR-interacting protein (RPGRIP1) gene allows the identification of mutations underlying Leber congenital amaurosis. Eur J Hum Genet 9:561–571PubMedCrossRefGoogle Scholar
  62. Gerding WM, Schreiber S, Schulte-Middelmann T, de Castro Marques A, Atorf J, Akkad DA, Dekomien G, Kremers J, Dermietzel R, Gal A, Rulicke T, Ibrahim S, Epplen JT, Petrasch-Parwez E (2011) Ccdc66 null mutation causes retinal degeneration and dysfunction. Hum Mol Genet 20(18):3620–3631PubMedCrossRefGoogle Scholar
  63. Goldstein O, Zangerl B, Pearce-Kelling S, Sidjanin DJ, Kijas JW, Felix J, Acland GM, Aguirre GD (2006) Linkage disequilibrium mapping in domestic dog breeds narrows the progressive rod–cone degeneration interval and identifies ancestral disease-transmitting chromosome. Genomics 88:541–550PubMedCrossRefGoogle Scholar
  64. Goldstein O, Guyon R, Kukekova A, Kuznetsova TN, Pearce-Kelling SE, Johnson J, Aguirre GD, Acland GM (2010a) COL9A2 and COL9A3 mutations in canine autosomal recessive oculoskeletal dysplasia. Mamm Genome 21:398–408PubMedCrossRefGoogle Scholar
  65. Goldstein O, Kukekova AV, Aguirre GD, Acland GM (2010b) Exonic SINE insertion in STK38L causes canine early retinal degeneration (erd). Genomics 96:362–368PubMedCrossRefGoogle Scholar
  66. Goldstein O, Mezey JG, Boyko AR, Gao C, Wang W, Bustamante CD, Anguish LJ, Jordan JA, Pearce-Kelling SE, Aguirre GD, Acland GM (2010c) An ADAM9 mutation in canine cone–rod dystrophy 3 establishes homology with human cone–rod dystrophy 9. Mol Vis 16:1549–1569PubMedGoogle Scholar
  67. Gould DJ, Petersen-Jones SM, Sohal A, Barnett KC, Sargan DR (1995) Investigation of the role of opsin gene polymorphism in generalized progressive retinal atrophies in dogs. Anim Genet 26:261–267PubMedGoogle Scholar
  68. Gould DJ, Petersen-Jones SM, Lin CT, Sargan DR (1997) Cloning of canine rom-1 and its investigation as a candidate gene for generalized progressive retinal atrophies in dogs. Anim Genet 28:391–396PubMedCrossRefGoogle Scholar
  69. Gray MM, Granka JM, Bustamante CD, Sutter NB, Boyko AR, Zhu L, Ostrander EA, Wayne RK (2009) Linkage disequilibrium and demographic history of wild and domestic canids. Genetics 181:1493–1505PubMedCrossRefGoogle Scholar
  70. Gu D, Beltran WA, Li Z, Acland GM, Aguirre GD (2007) Clinical light exposure, photoreceptor degeneration, and AP-1 activation: a cell death or cell survival signal in the rhodopsin mutant retina? Invest Ophthalmol Vis Sci 48:4907–4918PubMedCrossRefGoogle Scholar
  71. Guyon R, Lorentzen TD, Hitte C, Kim L, Cadieu E, Parker HG, Quignon P, Lowe JK, Renier C, Gelfenbeyn B, Vignaux F, DeFrance HB, Gloux S, Mahairas GG, André C, Galibert F, Ostrander EA (2003) A 1-Mb resolution radiation hybrid map of the canine genome. Proc Natl Acad Sci USA 100:5296–5301PubMedCrossRefGoogle Scholar
  72. Guyon R, Pearce-Kelling SE, Zeiss CJ, Acland GM, Aguirre GD (2007) Analysis of six candidate genes as potential modifiers of disease expression in canine XLPRA1, a model for human X-linked retinitis pigmentosa 3. Mol Vis 13:1094–1105PubMedGoogle Scholar
  73. Guziewicz KE, Zangerl B, Lindauer SJ, Mullins RF, Sandmeyer LS, Grahn BH, Stone EM, Acland GM, Aguirre GD (2007) Bestrophin gene mutations cause canine multifocal retinopathy: a novel animal model for best disease. Invest Ophthalmol Vis Sci 48:1959–1967PubMedCrossRefGoogle Scholar
  74. Hameed A, Abid A, Aziz A, Ismail M, Mehdi SQ, Khaliq S (2003) Evidence of RPGRIP1 gene mutations associated with recessive cone–rod dystrophy. J Med Genet 40:616–619PubMedCrossRefGoogle Scholar
  75. Hauswirth WW, Aleman TS, Kaushal S, Cideciyan AV, Schwartz SB, Wang L, Conlon TJ, Boye SL, Flotte TR, Byrne BJ, Jacobson SG (2008) Treatment of Leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum Gene Ther 19:979–990PubMedCrossRefGoogle Scholar
  76. Hunt DM, Buch P, Michaelides M (2010) Guanylate cyclases and associated activator proteins in retinal disease. Mol Cell Biochem 334:157–168PubMedCrossRefGoogle Scholar
  77. 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 39:1321–1328PubMedCrossRefGoogle Scholar
  78. Karlstam L, Hertil E, Zeiss C, Ropstad EO, Bjerkas E, Dubielzig RR, Ekesten B (2011) A slowly progressive retinopathy in the Shetland Sheepdog. Vet Ophthalmol 14:227–238PubMedCrossRefGoogle Scholar
  79. Keller RL, Kania SA, Hendrix DV, Ward DA, Abrams K (2006) Evaluation of canine serum for the presence of antiretinal autoantibodies in sudden acquired retinal degeneration syndrome. Vet Ophthalmol 9:195–200PubMedCrossRefGoogle Scholar
  80. Kijas JW, Cideciyan AV, Aleman TS, Pianta MJ, Pearce-Kelling SE, Miller BJ, Jacobson SG, Aguirre GD, Acland GM (2002) Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosa. Proc Natl Acad Sci USA 99:6328–6333PubMedCrossRefGoogle Scholar
  81. Kijas JW, Miller BJ, Pearce-Kelling SE, Aguirre GD, Acland GM (2003) Canine models of ocular disease: outcross breedings define a dominant disorder present in the English mastiff and bull mastiff dog breeds. J Hered 94:27–30PubMedCrossRefGoogle Scholar
  82. Kijas JW, Zangerl B, Miller B, Nelson J, Kirkness EF, Aguirre GD, Acland GM (2004) Cloning of the canine ABCA4 gene and evaluation in canine cone–rod dystrophies and progressive retinal atrophies. Mol Vis 10:223–232PubMedGoogle Scholar
  83. Kirkness EF, Bafna V, Halpern AL, Levy S, Remington K, Rusch DB, Delcher AL, Pop M, Wang W, Fraser CM, Venter JC (2003) The dog genome: survey sequencing and comparative analysis. Science 301:1898–1903PubMedCrossRefGoogle Scholar
  84. Klein W, Dekomien G, Holmes N, Epplen JT (1998) Evaluation of ROM1 as a candidate gene in generalised progressive retinal atrophy in dogs. Anim Genet 29:316–318PubMedCrossRefGoogle Scholar
  85. Komaromy AM, Alexander JJ, Rowlan JS, Garcia MM, Chiodo VA, Kaya A, Tanaka JC, Acland GM, Hauswirth WW, Aguirre GD (2010) Gene therapy rescues cone function in congenital achromatopsia. Hum Mol Genet 19:2581–2593PubMedCrossRefGoogle Scholar
  86. Kropatsch R, Petrasch-Parwez E, Seelow D, Schlichting A, Gerding WM, Akkad DA, Epplen JT, Dekomien G (2010) Generalized progressive retinal atrophy in the Irish Glen of Imaal Terrier is associated with a deletion in the ADAM9 gene. Mol Cell Probes 24(6):357–363PubMedCrossRefGoogle Scholar
  87. Kuchtey J, Olson LM, Rinkoski T, Mackay EO, Iverson TM, Gelatt KN, Haines JL, Kuchtey RW (2011) Mapping of the disease locus and identification of ADAMTS10 as a candidate gene in a canine model of primary open angle glaucoma. PLoS Genet 7:e1001306PubMedCrossRefGoogle Scholar
  88. Kukekova AV, Nelson J, Kuchtey RW, Lowe JK, Johnson JL, Ostrander EA, Aguirre GD, Acland GM (2006) Linkage mapping of canine rod cone dysplasia type 2 (rcd2) to CFA7, the canine orthologue of human 1q32. Invest Ophthalmol Vis Sci 47:1210–1215PubMedCrossRefGoogle Scholar
  89. Kukekova AV, Goldstein O, Johnson JL, Richardson MA, Pearce-Kelling SE, Swaroop A, Friedman JS, Aguirre GD, Acland GM (2009) Canine RD3 mutation establishes rod–cone dysplasia type 2 (rcd2) as ortholog of human and murine rd3. Mamm Genome 20:109–123PubMedCrossRefGoogle Scholar
  90. Langston AA, Mellersh CS, Neal CL, Ray K, Acland GM, Gibbs M, Aguirre GD, Fournier RE, Ostrander EA (1997) Construction of a panel of canine-rodent hybrid cell lines for use in partitioning of the canine genome. Genomics 46:317–325PubMedCrossRefGoogle Scholar
  91. Leskov IB, Klenchin VA, Handy JW, Whitlock GG, Govardovskii VI, Bownds MD, Lamb TD, Pugh EN Jr, Arshavsky VY (2000) The gain of rod phototransduction: reconciliation of biochemical and electrophysiological measurements. Neuron 27:525–537PubMedCrossRefGoogle Scholar
  92. Li R, Mignot E, Faraco J, Kadotani H, Cantanese J, Zhao B, Lin X, Hinton L, Ostrander EA, Patterson DF, de Jong PJ (1999) Construction and characterization of an eightfold redundant dog genomic bacterial artificial chromosome library. Genomics 58:9–17PubMedCrossRefGoogle Scholar
  93. Lin CT, Petersen-Jones SM, Sargan DR (1998) Isolation and investigation of canine phosducin as a candidate for canine generalized progressive retinal atrophies. Exp Eye Res 67:473–480PubMedCrossRefGoogle Scholar
  94. Lindblad-Toh K, Wade CM, Mikkelsen TS, Karlsson EK, Jaffe DB, Kamal M, Clamp M, Chang JL, Kulbokas EJ, 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 438:803–819PubMedCrossRefGoogle Scholar
  95. Lippmann T, Jonkisz A, Dobosz T, Petrasch-Parwez E, Epplen JT, Dekomien G (2007) Haplotype-defined linkage region for gPRA in Schapendoes dogs. Mol Vis 13:174–180PubMedGoogle Scholar
  96. Lowe JK, Kukekova AV, Kirkness EF, Langlois MC, Aguirre GD, Acland GM, Ostrander EA (2003) Linkage mapping of the primary disease locus for collie eye anomaly. Genomics 82:86–95PubMedCrossRefGoogle Scholar
  97. Magnusson H (1909) On night blindness in the dog following inbreeding. Svensk Vet Tidskr 14:462–466Google Scholar
  98. Magnusson H (1910) Retinitis pigmentosa and consanguinity in the dog. Svensk Vet Tidskr 15:378–380Google Scholar
  99. Magnusson H (1911) Über retinitis pigmentosa und Konsanguinität beim hunde. Arch Vergleichende Ophthal 2:147–163Google Scholar
  100. Magnusson H (1917) Noch ein fall von nachtblindheit beim hunde. Graefe’s Arch Ophthal 93:404–411CrossRefGoogle Scholar
  101. Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell’Osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J (2008) Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med 358:2240–2248PubMedCrossRefGoogle Scholar
  102. McWilliam P, Farrar GJ, Kenna P, Bradley DG, Humphries MM, Sharp EM, McConnell DJ, Lawler M, Sheils D, Ryan C et al (1989) Autosomal dominant retinitis pigmentosa (ADRP): localization of an ADRP gene to the long arm of chromosome 3. Genomics 5:619–622PubMedCrossRefGoogle Scholar
  103. Mellersh CS, Langston AA, Acland GM, Fleming MA, Ray K, Wiegand NA, Francisco LV, Gibbs M, Aguirre GD, Ostrander EA (1997) A linkage map of the canine genome. Genomics 46:326–336PubMedCrossRefGoogle Scholar
  104. Mellersh CS, Boursnell ME, Pettitt L, Ryder EJ, Holmes NG, Grafham D, Forman OP, Sampson J, Barnett KC, Blanton S, Binns MM, Vaudin M (2006) Canine RPGRIP1 mutation establishes cone–rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics 88:293–301PubMedCrossRefGoogle Scholar
  105. Meurs KM, Mauceli E, Lahmers S, Acland GM, White SN, Lindblad-Toh K (2010) Genome-wide association identifies a deletion in the 3′ untranslated region of striatin in a canine model of arrhythmogenic right ventricular cardiomyopathy. Hum Genet 128:315–324PubMedCrossRefGoogle Scholar
  106. Meyers VN, Jezyk PF, Aguirre GD, Patterson DF (1983) Short-limbed dwarfism and ocular defects in the samoyed dog. J Am Vet Med Assoc 183:975–979PubMedGoogle Scholar
  107. Miller PE, Galbreath EJ, Kehren JC, Steinberg H, Dubielzig RR (1998) Photoreceptor cell death by apoptosis in dogs with sudden acquired retinal degeneration syndrome. Am J Vet Res 59:149–152PubMedGoogle Scholar
  108. Miyadera K, Kato K, Aguirre-Hernandez J, Tokuriki T, Morimoto K, Busse C, Barnett K, Holmes N, Ogawa H, Sasaki N, Mellersh CS, Sargan DR (2009) Phenotypic variation and genotype–phenotype discordance in canine cone–rod dystrophy with an RPGRIP1 mutation. Mol Vis 15:2287–2305PubMedGoogle Scholar
  109. Miyadera K, Kato K, Boursnell M, Mellersh CS, Sargan DR (2012) Genome-wide association study in RPGRIP1−/− dogs identifies a modifier locus that determines the onset of retinal degeneration. Mamm Genome (under revision)Google Scholar
  110. Mollet G, Salomon R, Gribouval O, Silbermann F, Bacq D, Landthaler G, Milford D, Nayir A, Rizzoni G, Antignac C, Saunier S (2002) The gene mutated in juvenile nephronophthisis type 4 encodes a novel protein that interacts with nephrocystin. Nat Genet 32:300–305PubMedCrossRefGoogle Scholar
  111. Moody JA, Famula TR, Sampson RC, Murphy KE (2005) Identification of microsatellite markers linked to progressive retinal atrophy in American Eskimo Dogs. Am J Vet Res 66:1900–1902PubMedCrossRefGoogle Scholar
  112. Mowat FM, Petersen-Jones SM, Williamson H, Williams DL, Luthert PJ, Ali RR, Bainbridge JW (2008) Topographical characterization of cone photoreceptors and the area centralis of the canine retina. Mol Vis 14:2518–2527PubMedGoogle Scholar
  113. Narfström K, Wrigstad A, Nilsson SEG (1989) The Briard dog: a new animal model of congenital stationary night blindness. Br J Ophthalmol 73:750–756PubMedCrossRefGoogle Scholar
  114. Narfström K, Katz ML, Bragadottir R, Seeliger M, Boulanger A, Redmond TM, Caro L, Lai CM, Rakoczy PE (2003) Functional and structural recovery of the retina after gene therapy in the RPE65 null mutation dog. Invest Ophthalmol Vis Sci 44:1663–1672PubMedCrossRefGoogle Scholar
  115. Narfström K, Seeliger M, Lai CM, Vaegan, Katz M, Rakoczy EP, Reme C (2008) Morphological aspects related to long-term functional improvement of the retina in the 4 years following rAAV-mediated gene transfer in the RPE65 null mutation dog. Adv Exp Med Biol 613:139–146PubMedCrossRefGoogle Scholar
  116. Nathans J, Thomas D, Hogness DS (1986a) Molecular genetics of human color vision: the genes encoding blue, green, and red pigments. Science 232:193–202PubMedCrossRefGoogle Scholar
  117. Nathans J, Piantanida TP, Eddy RL, Shows TB, Hogness DS (1986b) Molecular genetics of inherited variation in human color vision. Science 232:203–210PubMedCrossRefGoogle Scholar
  118. Nawrot M, Liu T, Garwin GG, Crabb JW, Saari JC (2006) Scaffold proteins and the regeneration of visual pigments. Photochem Photobiol 82:1482–1488PubMedGoogle Scholar
  119. Nelson D, MacMillan A (1983) Multifocal retinal dysplasia in field trial Labrador retrievers. J Am Anim Hosp Assoc 19:388Google Scholar
  120. Nevet MJ, Shalev SA, Zlotogora J, Mazzawi N, Ben-Yosef T (2010) Identification of a prevalent founder mutation in an Israeli Muslim Arab village confirms the role of PRCD in the aetiology of retinitis pigmentosa in humans. J Med Genet 47:533–537PubMedCrossRefGoogle Scholar
  121. O’Toole D, Roberts S, Nunamaker C (1992) Sudden acquired retinal degeneration (‘silent retina syndrome’) in two dogs. Vet Rec 130:157–161PubMedCrossRefGoogle Scholar
  122. Olsson M, Meadows JR, Truve K, Rosengren Pielberg G, Puppo F, Mauceli E, Quilez J, Tonomura N, Zanna G, Docampo MJ, Bassols A, Avery AC, Karlsson EK, Thomas A, Kastner DL, Bongcam-Rudloff E, Webster MT, Sanchez A, Hedhammar A, Remmers EF, Andersson L, Ferrer L, Tintle L, Lindblad-Toh K (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:e1001332PubMedCrossRefGoogle Scholar
  123. Otto E, Hoefele J, Ruf R, Mueller AM, Hiller KS, Wolf MT, Schuermann MJ, Becker A, Birkenhager R, Sudbrak R, Hennies HC, Nurnberg P, Hildebrandt F (2002) A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution. Am J Hum Genet 71:1161–1167PubMedCrossRefGoogle Scholar
  124. Parker HG, Kim LV, Sutter NB, Carlson S, Lorentzen TD, Malek TB, Johnson GS, DeFrance HB, Ostrander EA, Kruglyak L (2004) Genetic structure of the purebred domestic dog. Science 304:1160–1164PubMedCrossRefGoogle Scholar
  125. Parker HG, Kukekova AV, Akey DT, Goldstein O, Kirkness EF, Baysac KC, Mosher DS, Aguirre GD, Acland GM, Ostrander EA (2007) Breed relationships facilitate fine-mapping studies: a 7.8-kb deletion cosegregates with Collie eye anomaly across multiple dog breeds. Genome Res 17:1562–1571PubMedCrossRefGoogle Scholar
  126. Parker HG, VonHoldt BM, Quignon P, Margulies EH, Shao S, Mosher DS, Spady TC, Elkahloun A, Cargill M, Jones PG, Maslen CL, Acland GM, Sutter NB, Kuroki K, Bustamante CD, Wayne RK, Ostrander EA (2009) An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. Science 325:995–998PubMedCrossRefGoogle Scholar
  127. Parry HB (1953a) Degenerations of the dog retina. I. Structure and development of the retina of the normal dog. Br J Ophthalmol 37:385–404PubMedCrossRefGoogle Scholar
  128. Parry HB (1953b) Degenerations of the dog retina. II. Generalized progressive atrophy of hereditary origin. Br J Ophthalmol 37:487–502PubMedCrossRefGoogle Scholar
  129. Parry HB (1954a) Degenerations of the dog retina. IV. Retinopathies associated with dog distemper-complex virus infections. Br J Ophthalmol 38:295–309PubMedCrossRefGoogle Scholar
  130. Parry HB (1954b) Degenerations of the dog retina. VI. Central progressive atrophy with pigment epithelial dystrophy. Br J Ophthalmol 38:653–668PubMedCrossRefGoogle Scholar
  131. Parry HB, Tansley K, Thomson LC (1953) The electroretinogram of the dog. J Physiol 120:28–40PubMedGoogle Scholar
  132. Parry HB, Tansley K, Thomson LC (1955) Electroretinogram during development of hereditary retinal degeneration in the dog. Br J Ophthalmol 39:349–352PubMedCrossRefGoogle Scholar
  133. Parry DA, Toomes C, Bida L, Danciger M, Towns KV, McKibbin M, Jacobson SG, Logan CV, Ali M, Bond J, Chance R, Swendeman S, Daniele LL, Springell K, Adams M, Johnson CA, Booth AP, Jafri H, Rashid Y, Banin E, Strom TM, Farber DB, Sharon D, Blobel CP, Pugh EN Jr, Pierce EA, Inglehearn CF (2009) Loss of the metalloprotease ADAM9 leads to cone–rod dystrophy in humans and retinal degeneration in mice. Am J Hum Genet 84:683–691PubMedCrossRefGoogle Scholar
  134. Parshall CJ, Wyman M, Nitroy S, Acland G, Aguirre G (1991) Photoreceptor dysplasia: an inherited progressive retinal atrophy of Miniature Schnauzer dogs. Progr Vet Comp Ophthalmol 1:187–203Google Scholar
  135. Petersen-Jones SM, Entz DD, Sargan DR (1999) cGMP phosphodiesterase-α mutation causes progressive retinal atrophy in the cardigan Welsh corgi dog. Invest Ophthalmol Vis Sci 40:1637–1644PubMedGoogle Scholar
  136. Priat C, Hitte C, Vignaux F, Renier C, Jiang Z, Jouquand S, Chéron A, André C, Galibert F (1998) A whole-genome radiation hybrid map of the dog genome. Genomics 54:361–378PubMedCrossRefGoogle Scholar
  137. Pugh EN Jr (1999) Variability in single photon responses: a cut in the Gordian knot of rod phototransduction? Neuron 23:205–208PubMedCrossRefGoogle Scholar
  138. Ray K, Baldwin VJ, Acland GM, Blanton SH, Aguirre GD (1994) Cosegregation of codon 807 mutation of the canine rod cGMP phosphodiesterase ß gene and rcd1. Invest Ophthalmol Vis Sci 35:4291–4299PubMedGoogle Scholar
  139. Ray K, Acland GM, Aguirre GD (1996) Nonallelism of erd and prcd and exclusion of the canine RDS/peripherin gene as a candidate for both retinal degeneration loci. Invest Ophthalmol Vis Sci 37:783–794PubMedGoogle Scholar
  140. Ray K, Wang W, Czarnecki J, Zhang Q, Acland GM, Aguirre GD (1999) Strategies for identification of mutations causing hereditary retinal diseases in dogs: evaluation of opsin as a candidate gene. J Hered 90:133–137PubMedCrossRefGoogle Scholar
  141. Roberts S (1969) The collie eye anomaly. J Am Vet Med Assoc 155:859–878Google Scholar
  142. Ropstad EO, Bjerkas E, Narfstrom K (2007) Clinical findings in early onset cone–rod dystrophy in the standard wire-haired dachshund. Vet Ophthalmol 10:69–75PubMedCrossRefGoogle Scholar
  143. Ropstad EO, Narfstrom K, Lingaas F, Wiik C, Bruun A, Bjerkas E (2008) Functional and structural changes in the retina of wire-haired dachshunds with early-onset cone–rod dystrophy. Invest Ophthalmol Vis Sci 49:1106–1115PubMedCrossRefGoogle Scholar
  144. Rubin L (1968) Heredity of retinal dysplasia in bedlington terriers. J Am Vet Med Assoc 152:260–262Google Scholar
  145. Rubin L, Bourns T, Lord L (1967) Hemeralopia in dogs: heredity of hemeralopia in Alaskan malamutes. Am J Vet Res 28:355–357PubMedGoogle Scholar
  146. Runte M, Dekomien G, Epplen JT (2000) Evaluation of RDS/Peripherin and ROM1 as candidate genes in generalised progressive retinal atrophy and exclusion of digenic inheritance. Anim Genet 31:223–227PubMedCrossRefGoogle Scholar
  147. Salmon Hillbertz NH, Isaksson M, Karlsson EK, Hellmen E, Pielberg GR, Savolainen P, Wade CM, von Euler H, Gustafson U, Hedhammar A, Nilsson M, Lindblad-Toh K, Andersson L, Andersson G (2007) Duplication of FGF3, FGF4, FGF19 and ORAOV1 causes hair ridge and predisposition to dermoid sinus in Ridgeback dogs. Nat Genet 39:1318–1320PubMedCrossRefGoogle Scholar
  148. Sidjanin DJ, Lowe JK, McElwee JL, Milne BS, Phippen TM, Sargan DR, Aguirre GD, Acland GM, Ostrander EA (2002) Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3. Hum Mol Genet 11:1823–1833PubMedCrossRefGoogle Scholar
  149. Sidjanin DJ, Miller B, Kijas J, McElwee J, Pillardy J, Malek J, Pai G, Feldblyum T, Fraser C, Acland G, Aguirre G (2003) Radiation hybrid map, physical map, and low-pass genomic sequence of the canine prcd region on CFA9 and comparative mapping with the syntenic region on human chromosome 17. Genomics 81:138–148PubMedCrossRefGoogle Scholar
  150. Stone EM (2007) Leber congenital amaurosis—a model for efficient genetic testing of heterogeneous disorders: LXIV Edward Jackson Memorial Lecture. Am J Ophthalmol 144:791–811PubMedCrossRefGoogle Scholar
  151. Suber ML, Pittler SJ, Qin N, Wright GC, Holcombe V, Lee RH, Craft CM, Lolley RN, Baehr W, Hurwitz RL (1993) Irish setter dogs affected with rod/cone dysplasia contain a nonsense mutation in the rod cGMP phosphodiesterase ß-subunit gene. Proc Natl Acad Sci USA 90:3968–3972PubMedCrossRefGoogle Scholar
  152. Sutter NB, Eberle MA, Parker HG, Pullar BJ, Kirkness EF, Kruglyak L, Ostrander EA (2004) Extensive and breed-specific linkage disequilibrium in Canis familiaris. Genome Res 14:2388–2396PubMedCrossRefGoogle Scholar
  153. Turney C, Chong NH, Alexander RA, Hogg CR, Fleming L, Flack D, Barnett KC, Bird AC, Holder GE, Luthert PJ (2007) Pathological and electrophysiological features of a canine cone–rod dystrophy in the miniature longhaired dachshund. Invest Ophthalmol Vis Sci 48:4240–4249PubMedCrossRefGoogle Scholar
  154. Vainisi SJ, Schmidt GM, West CS et al (1983) Metabolic toxic retinopathy preliminary report. Trans Am Coll Vet Ophthalmol 14:76–81Google Scholar
  155. van der Woerdt A, Nasisse M, Davidson M (1991) Sudden acquired retinal degeneration in the dog: clinical and laboratory in 36 cases. Prog Vet Comp Ophthalmol 1:11–18Google Scholar
  156. van Wijk E, van der Zwaag B, Peters T, Zimmermann U, Te Brinke H, Kersten FF, Marker T, Aller E, Hoefsloot LH, Cremers CW, Cremers FP, Wolfrum U, Knipper M, Roepman R, Kremer H (2006) The DFNB31 gene product whirlin connects to the Usher protein network in the cochlea and retina by direct association with USH2A and VLGR1. Hum Mol Genet 15:751–765PubMedCrossRefGoogle Scholar
  157. van Wijk E, Kersten FF, Kartono A, Mans DA, Brandwijk K, Letteboer SJ, Peters TA, Marker T, Yan X, Cremers CW, Cremers FP, Wolfrum U, Roepman R, Kremer H (2009) Usher syndrome and Leber congenital amaurosis are molecularly linked via a novel isoform of the centrosomal ninein-like protein. Hum Mol Genet 18:51–64PubMedCrossRefGoogle Scholar
  158. Veske A, Nilsson SEG, Narfström K, Gal A (1999) Retinal dystrophy of Swedish briard/briard-beagle dogs is due to a 4-bp deletion in RPE65. Genomics 57:57–61PubMedCrossRefGoogle Scholar
  159. 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 (2010) Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication. Nature 464:898–902PubMedCrossRefGoogle Scholar
  160. Wang W, Acland GM, Ray K, Aguirre GD (1999) Evaluation of cGMP-phosphodiesterase (PDE) subunits for causal association with rod–cone dysplasia 2 (rcd2), a canine model of abnormal retinal cGMP metabolism. Exp Eye Res 69:445–453PubMedCrossRefGoogle Scholar
  161. Wang P, Zangerl B, Werner P, Mauldin EA, Casal ML (2011) Familial cutaneous lupus erythematosus (CLE) in the German shorthaired pointer maps to CFA18, a canine orthologue to human CLE. Immunogenetics 63:197–207PubMedCrossRefGoogle Scholar
  162. Wiik AC, Wade C, Biagi T, Ropstad EO, Bjerkas E, Lindblad-Toh K, Lingaas F (2008) A deletion in nephronophthisis 4 (NPHP4) is associated with recessive cone–rod dystrophy in standard wire-haired dachshund. Genome Res 18(9):1415–1421PubMedCrossRefGoogle Scholar
  163. 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 42:250–254PubMedCrossRefGoogle Scholar
  164. Wood SH, Ke X, Nuttall T, McEwan N, Ollier WE, Carter SD (2009) Genome-wide association analysis of canine atopic dermatitis and identification of disease related SNPs. Immunogenetics 61:765–772PubMedCrossRefGoogle Scholar
  165. Woodford B, Liu Y, Fletcher R, Chader G, Farber D, Santos-Anderson R, Tso M (1982) Cyclic nucleotide metabolism in inherited retinopathy in collies: a biochemical and histochemical study. Exp Eye Res 34:703–714PubMedCrossRefGoogle Scholar
  166. Wrigstad A (1994) Hereditary dystrophy of the retina and the retinal pigment epithelium in a strain of briard dogs: a clinical, morphological and electrophysiological study. In: Linköping University Medical DissertationsGoogle Scholar
  167. Wrigstad A, Narfstrom K, Nilsson SEG (1994) Slowly progressive changes of the retina and retinal pigment epithelium in briard dogs with hereditary congenital night blindness and partial day blindness. a morphological study. Doc Ophthalmol 87:337–354PubMedCrossRefGoogle Scholar
  168. Zangerl B, Zhang Q, Pearce-Kelling SE, Aguirre GD (2002) Molecular cloning, characterization and mapping of the canine glucocorticoid receptor DNA binding factor 1 (GRLF1). GENE 294:167–176PubMedCrossRefGoogle Scholar
  169. Zangerl B, Goldstein O, Philp AR, Lindauer SJ, Pearce-Kelling SE, Mullins RF, Graphodatsky AS, Ripoll D, Felix JS, Stone EM, Acland GM, Aguirre GD (2006) Identical mutation in a novel retinal gene causes progressive rod–cone degeneration in dogs and retinitis pigmentosa in humans. Genomics 88:551–563PubMedCrossRefGoogle Scholar
  170. Zangerl B, Johnson JL, Pillardy J, Sun Q, Andre C, Galibert F, Acland GM, Aguirre GD (2009) Comparative genomic mapping of uncharacterized canine retinal ESTs to identify novel candidate genes for hereditary retinal disorders. Mol Vis 15:927–936PubMedGoogle Scholar
  171. Zangerl B, Wickstrom K, Slavik J, Lindauer SJ, Ahonen S, Schelling C, Lohi H, Guziewicz KE, Aguirre GD (2010) Assessment of canine BEST1 variations identifies new mutations and establishes an independent bestrophinopathy model (cmr3). Mol Vis 16:2791–2804PubMedGoogle Scholar
  172. Zeiss CJ, Acland GM, Aguirre GD (1999) Retinal pathology of canine X-linked progressive retinal atrophy, the locus homologue of RP3. Invest Ophthalmol Vis Sci 40:3292–3304PubMedGoogle Scholar
  173. Zeng R, Farias FH, Johnson GS, McKay SD, Schnabel RD, Decker JE, Taylor JF, Mann CS, Katz ML, Johnson GC, Coates JR, O’Brien DP (2011) A truncated retrotransposon disrupts the GRM1 coding sequence in Coton de Tulear dogs with Bandera’s neonatal ataxia. J Vet Intern Med 25:267–272PubMedCrossRefGoogle Scholar
  174. Zernant J, Kulm M, Dharmaraj S, den Hollander AI, Perrault I, Preising MN, Lorenz B, Kaplan J, Cremers FP, Maumenee I, Koenekoop RK, Allikmets R (2005) Genotyping microarray (disease chip) for Leber congenital amaurosis: detection of modifier alleles. Invest Ophthalmol Vis Sci 46:3052–3059PubMedCrossRefGoogle Scholar
  175. Zhang Q, Acland GM, Parshall CJ, Haskell J, Ray K, Aguirre GD (1998) Characterization of canine photoreceptor phosducin cDNA and identification of a sequence variant in dogs with photoreceptor dysplasia. Gene 215:231–239PubMedCrossRefGoogle Scholar
  176. Zhang Q, Ray K, Acland GM, Czarnecki JM, Aguirre GD (2000) Molecular cloning, characterization and expression of a novel retinal clusterin-like protein cDNA. Gene 243:151–160PubMedCrossRefGoogle Scholar
  177. Zhang Q, Acland GM, Zangerl B, Johnson JL, Mao Z, Zeiss CJ, Ostrander EA, Aguirre GD (2001) Fine mapping of canine XLPRA establishes homology of the human and canine RP3 intervals. Invest Ophthalmol Vis Sci 42:2466–2471PubMedGoogle Scholar
  178. Zhang Q, Acland GM, Wu WX, Johnson JL, Pearce-Kelling S, Tulloch B, Vervoort R, Wright AF, Aguirre GD (2002) Different RPGR exon ORF15 mutations in Canids provide insights into photoreceptor cell degeneration. Hum Mol Genet 11:993–1003PubMedCrossRefGoogle Scholar
  179. Zhou Z, Sheng X, Zhang Z, Zhao K, Zhu L, Guo G, Friedenberg SG, Hunter LS, Vandenberg-Foels WS, Hornbuckle WE, Krotscheck U, Corey E, Moise NS, Dykes NL, Li J, Xu S, Du L, Wang Y, Sandler J, Acland GM, Lust G, Todhunter RJ (2010) Differential genetic regulation of canine hip dysplasia and osteoarthritis. PLoS One 5:e13219PubMedCrossRefGoogle Scholar
  180. Zhu L, Jang GF, Jastrzebska B, Filipek S, Pearce-Kelling SE, Aguirre GD, Stenkamp RE, Acland GM, Palczewski K (2004) A naturally occurring mutation of the opsin gene (T4R) in dogs affects glycosylation and stability of the G protein-coupled receptor. J Biol Chem 279:53828–53839PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Keiko Miyadera
    • 1
  • Gregory M. Acland
    • 2
  • Gustavo D. Aguirre
    • 1
    Email author
  1. 1.Section of Ophthalmology, Department of Clinical StudiesSchool of Veterinary Medicine, University of PennsylvaniaPhiladelphiaUSA
  2. 2.James A. Baker Institute for Animal HealthCollege of Veterinary Medicine, Cornell UniversityIthacaUSA

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