Genome-wide association and linkage analyses localize a progressive retinal atrophy locus in Persian cats.
Hereditary eye diseases of animals serve as excellent models of human ocular disorders and assist in the development of gene and drug therapies for inherited forms of blindness. Several primary hereditary eye conditions affecting various ocular tissues and having different rates of progression have been documented in domestic cats. Gene therapy for canine retinopathies has been successful, thus the cat could be a gene therapy candidate for other forms of retinal degenerations. The current study investigates a hereditary, autosomal recessive, retinal degeneration specific to Persian cats. A multi-generational pedigree segregating for this progressive retinal atrophy was genotyped using a 63 K SNP array and analyzed via genome-wide linkage and association methods. A multi-point parametric linkage analysis localized the blindness phenotype to a ~1.75 Mb region with significant LOD scores (Z ≈ 14, θ = 0.00) on cat chromosome E1. Genome-wide TDT, sib-TDT, and case-control analyses also consistently supported significant association within the same region on chromosome E1, which is homologous to human chromosome 17. Using haplotype analysis, a ~1.3 Mb region was identified as highly associated for progressive retinal atrophy in Persian cats. Several candidate genes within the region are reasonable candidates as a potential causative gene and should be considered for molecular analyses.
Department of Population Health and Reproduction, School of Veterinary Medicine, University of California - Davis, Davis, CA, 95616, USA.
Hasan
H
Alhaddad
Barbara
B
Gandolfi
Robert A
RA
Grahn
Hyung-Chul
HC
Rah
Carlyn B
CB
Peterson
David J
DJ
Maggs
Kathryn L
KL
Good
Niels C
NC
Pedersen
Leslie A
LA
Lyons
D000818:Animals; D001284:Atrophy; D016022:Case-Control Studies; D002371:Cat Diseases / Q000235:genetics*; D002415:Cats; D033481:Chromosomes, Mammalian / Q000235:genetics; D018450:Disease Progression; D004285:Dogs; D005260:Female; D056726:Genetic Association Studies; D008040:Genetic Linkage; D056426:Genetic Loci; D005819:Genetic Markers; D016678:Genome / Q000235:genetics; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D010375:Pedigree; D019071:Persia; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012162:Retinal Degeneration / Q000235:genetics* / Q000662:veterinary*
D005819:Genetic Markers