A tool set to allow rapid screening of dog families with PRA for association with candidate genes.
OBJECTIVE
To develop a method to rapidly screen candidate genes for association with recessively inherited progressive retinal atrophy (PRA) in pedigrees of dog in which a causative mutation has not been identified.


METHODS
Thirteen PRA-affected dogs were used in this study.


METHODS
Two microsatellite markers (MS) were designed flanking 45 candidate genes. MS markers were analyzed for heterozygosity and allelic richness. Two dog breeds, in which the causative mutation has been identified (Entlebucher Sennenhunds [ES] and PDE6A-mutant dogs [PDE6A]), were used to validate the MS marker panel. One breed in which the causative mutation is currently unknown (Old English Sheepdog [OES]) was investigated in this study utilizing the MS panel.


RESULTS
Marker heterozygosity excluded 38 of 45 and 41 of 45 candidate genes (ES and PDE6A, respectively) with each true culprit gene remaining on the list of nonexcluded candidate genes. Additionally, 41 of 45 genes were excluded for OES.


CONCLUSIONS
This tool set was used quickly and efficiently to narrow down 45 candidate genes for recessively inherited PRA in two types of dogs with known mutations and one type of dog with an unknown mutation.
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, 48824, USA.|Genetics Program, Michigan State University, East Lansing, MI, 48824, USA.
Paige A
PA
Winkler
Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Jennifer A
JA
Davis
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, 48824, USA.|Genetics Program, Michigan State University, East Lansing, MI, 48824, USA.
Simon M
SM
Petersen-Jones
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, 48824, USA.|Genetics Program, Michigan State University, East Lansing, MI, 48824, USA.|Microbiology & Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA.
Patrick J
PJ
Venta
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, 48824, USA.
Joshua T
JT
Bartoe
D000818:Animals; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005808:Genes, Recessive; D056726:Genetic Association Studies / Q000662:veterinary; D009154:Mutation; D010375:Pedigree; D012162:Retinal Degeneration / Q000235:genetics / Q000662:veterinary*; D013045:Species Specificity
Leber congenital amaurosis; exclusion analysis; progressive retinal atrophy; retinitis pigmentosa