Indirect exclusion of four candidate genes for generalized progressive retinal atrophy in several breeds of dogs.
BACKGROUND
Generalized progressive retinal atrophy (gPRA) is a hereditary ocular disorder with progressive photoreceptor degeneration in dogs. Four retina-specific genes, ATP binding cassette transporter retina (ABCA4), connexin 36 (CX36), c-mer tyrosin kinase receptor (MERTK) and photoreceptor cell retinol dehydrogenase (RDH12) were investigated in order to identify mutations leading to autosomal recessive (ar) gPRA in 29 breeds of dogs.


RESULTS
Mutation screening was performed initially by PCR and single strand conformation polymorphism (SSCP) analysis, representing a simple method with comparatively high reliability for identification of sequence variations in many samples. Conspicuous banding patterns were analyzed via sequence analyses in order to detect the underlying nucleotide variations. No pathogenetically relevant mutations were detected in the genes ABCA4, CX36, MERTK and RDH12 in 71 affected dogs of 29 breeds. Yet 30 new sequence variations were identified, both, in the coding regions and intronic sequences. Many of the sequence variations were in heterozygous state in affected dogs.


CONCLUSIONS
Based on the ar transmittance of gPRA in the breeds investigated, informative sequence variations provide evidence allowing indirect exclusion of pathogenetic mutations in the genes ABCA4 (for 9 breeds), CX36 (for 12 breeds), MERTK (for all 29 breeds) and RDH12 (for 9 breeds).
Lippmann
Tanja
T
Human Genetics, Ruhr-University Bochum, Germany. tanja.lippmann@t-online.de
Pasternack
Sandra M
SM
Kraczyk
Britta
B
Dudek
Sabine E
SE
Dekomien
Gabriele
G
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000429:Alcohol Oxidoreductases / Q000235:genetics; D000818:Animals; D001284:Atrophy; D017630:Connexins / Q000235:genetics; D004252:DNA Mutational Analysis; D004283:Dog Diseases / Q000235:genetics* / Q000473:pathology*; D004285:Dogs / Q000235:genetics*; D014644:Genetic Variation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012160:Retina / Q000473:pathology*; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D013045:Species Specificity; D000097004:Gap Junction delta-2 Protein
D018528:ATP-Binding Cassette Transporters; D000429:Alcohol Oxidoreductases; D017630:Connexins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000097004:Gap Junction delta-2 Protein