title: A non-stop S-antigen gene mutation is associated with late onset hereditary retinal degeneration in dogs.
abstract: OBJECTIVE
  To identify the causative mutation of canine progressive retinal atrophy (PRA) segregating as an adult onset autosomal recessive disorder in the Basenji breed of dog.
  
  
  METHODS
  Basenji dogs were ascertained for the PRA phenotype by clinical ophthalmoscopic examination. Blood samples from six affected cases and three nonaffected controls were collected, and DNA extraction was used for a genome-wide association study using the canine HD Illumina single nucleotide polymorphism (SNP) array and PLINK. Positional candidate genes identified within the peak association signal region were evaluated.
  
  
  RESULTS
  The highest -Log10(P) value of 4.65 was obtained for 12 single nucleotide polymorphisms on three chromosomes. Homozygosity and linkage disequilibrium analyses favored one chromosome, CFA25, and screening of the S-antigen (SAG) gene identified a non-stop mutation (c.1216T>C), which would result in the addition of 25 amino acids (p.*405Rext*25).
  
  
  CONCLUSIONS
  Identification of this non-stop SAG mutation in dogs affected with retinal degeneration establishes this canine disease as orthologous to Oguchi disease and SAG-associated retinitis pigmentosa in humans, and offers opportunities for genetic therapeutic intervention.
authors.affiliation: Baker Institute for Animal Health, Cornell University College of Veterinary Medicine, Ithaca, NY.
authors.forename: Orly
authors.initials: O
authors.lastname: Goldstein
authors.forename: Julie Ann
authors.initials: JA
authors.lastname: Jordan
authors.forename: Gustavo D
authors.initials: GD
authors.lastname: Aguirre
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Acland
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019393:Arrestin / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D018389:Codon, Nonsense / Q000235:genetics; D004285:Dogs; D005260:Female; D005654:Fundus Oculi; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006720:Homozygote; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics* / Q000662:veterinary*
chemical_list: D019393:Arrestin; D018389:Codon, Nonsense; D012333:RNA, Messenger
references.citation: Eur J Ophthalmol. 2012 Jul-Aug;22(4):647-53
references.pmid: 22180149
references.citation: PLoS One. 2012;7(3):e33549
references.pmid: 22457775
references.citation: Nat Genet. 2009 Oct;41(10):1122-6
references.pmid: 19767754
references.citation: Curr Opin Cell Biol. 2002 Apr;14(2):189-95
references.pmid: 11891118
references.citation: Retina. 1997;17(1):17-22
references.pmid: 9051837
references.citation: Hum Mutat. 1998;Suppl 1:S317-9
references.pmid: 9452120
references.citation: Mamm Genome. 2012 Feb;23(1-2):203-11
references.pmid: 22105877
references.citation: Curr Eye Res. 1997 Mar;16(3):270-4
references.pmid: 9088745
references.citation: Mol Vis. 2012;18:528-36
references.pmid: 22419846
references.citation: Am J Ophthalmol. 1998 Feb;125(2):249-51
references.pmid: 9467455
references.citation: Arch Ophthalmol. 1998 Apr;116(4):498-501
references.pmid: 9565049
references.citation: Invest Ophthalmol Vis Sci. 2007 May;48(5):1942-51
references.pmid: 17460245
references.citation: Eye (Lond). 2011 Aug;25(8):1098-101
references.pmid: 21494281
references.citation: Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18690-5
references.pmid: 22039220
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5233-8
references.pmid: 15784735
references.citation: PLoS One. 2011;6(6):e21452
references.pmid: 21738669
references.citation: Am J Hum Genet. 2008 Jan;82(1):174-80
references.pmid: 18179896
references.citation: Arch Ophthalmol. 1965 May;73:646-56
references.pmid: 14281981
references.citation: Genomics. 2006 Nov;88(5):541-50
references.pmid: 16859891
references.citation: Doc Ophthalmol. 2011 Oct;123(2):127-33
references.pmid: 21922265
references.citation: Croat Med J. 2009 Feb;50(1):23-33
references.pmid: 19260141
references.citation: J Mol Biol. 2005 Dec 16;354(5):1069-80
references.pmid: 16289201
references.citation: Am J Ophthalmol. 1969 Jul;68(1):19-26
references.pmid: 5306121
references.citation: Expert Rev Mol Med. 2010 Apr 23;12:e13
references.pmid: 20412604
references.citation: Ophthalmology. 2004 Jul;111(7):1410-4
references.pmid: 15234147
references.citation: Nat Genet. 2010 Aug;42(8):692-7
references.pmid: 20622881
references.citation: Am J Hum Genet. 2012 Jan 13;90(1):102-9
references.pmid: 22177090
references.citation: J Biol Chem. 2004 Dec 17;279(51):53828-39
references.pmid: 15459196
references.citation: Hum Genomics. 2011 May;5(4):241-64
references.pmid: 21712188
references.citation: Jpn J Ophthalmol. 1996;40(4):511-9
references.pmid: 9130055
references.citation: Mov Disord. 2011 Apr;26(5):858-61
references.pmid: 21425335
references.citation: BMC Med Genet. 2011 Aug 03;12:104
references.pmid: 21812969
references.citation: Invest Ophthalmol Vis Sci. 1999 Nov;40(12):2978-82
references.pmid: 10549660
references.citation: Nature. 2010 Apr 8;464(7290):898-902
references.pmid: 20237475
references.citation: Structure. 2001 Sep;9(9):869-80
references.pmid: 11566136
references.citation: FEBS Lett. 1984 Oct 29;176(2):473-8
references.pmid: 6436059
references.citation: Nat Genet. 1995 Jul;10(3):360-2
references.pmid: 7670478
references.citation: Neuron. 2000 Oct;28(1):153-64
references.pmid: 11086991
references.citation: Am J Hum Genet. 2011 Jul 15;89(1):183-90
references.pmid: 21763485
references.citation: Genomics. 2006 Nov;88(5):551-63
references.pmid: 16938425
references.citation: Jpn J Ophthalmol. 2004 Jul-Aug;48(4):350-2
references.pmid: 15295660
references.citation: Am J Hum Genet. 2010 Feb 12;86(2):285-91
references.pmid: 20159113
references.citation: PLoS One. 2013;8(3):e60149
references.pmid: 23527306
references.citation: PLoS One. 2013;8(3):e57195
references.pmid: 23469184
references.citation: Mol Vis. 2012;18:1253-9
references.pmid: 22665972
references.citation: Mamm Genome. 2010 Aug;21(7-8):398-408
references.pmid: 20686772
references.citation: Biochemistry. 2002 Mar 12;41(10):3321-8
references.pmid: 11876640
references.citation: Cell. 1999 Apr 16;97(2):257-69
references.pmid: 10219246
references.citation: Am J Hum Genet. 2007 Sep;81(3):559-75
references.pmid: 17701901
references.citation: Genome Med. 2009 Jan 22;1(1):13
references.pmid: 19348700
references.citation: Mol Vis. 2010 Aug 11;16:1549-69
references.pmid: 20806078
references.citation: Mamm Genome. 2012 Feb;23(1-2):40-61
references.pmid: 22065099