Generalized progressive retinal atrophy in the Irish Glen of Imaal Terrier is associated with a deletion in the ADAM9 gene.
Generalized progressive retinal atrophy (gPRA) belongs to a group of inherited retinal diseases which are associated with gradual vision loss in various dog breeds, including the Irish Glen of Imaal Terrier (GIT). By genome-wide homozygosity mapping using SNP arrays and fine mapping of candidate regions, we assigned the gPRA candidate locus in this breed to canine chromosome 16. The respective region is syntenic with human chromosome 8 comprising the ADAM metallopeptidase domain 9 (ADAM9) gene. ADAM9 represents a strong candidate gene for canine retinal disease because mutations have previously been shown to cause autosomal recessively inherited human cone-rod dystrophy, a retinal disorder affecting photoreceptor function. Sequence analysis of ADAM9 in affected and carrier GITs revealed a deletion of exons 15 and 16 which alters the reading frame leading to a premature stop codon. This mutation was absent from 34 other dog breeds. A variable and, at times, very late onset of gPRA was confirmed in GITs by a relatively mild retinal degeneration at an advanced age. Hence, the identification of the genetic defect underlying gPRA in the GIT represents a suitable model for cone-rod dystrophy of humans, with superior potential to elucidate functional consequences of the recently described null mutations in the human ADAM9 gene.
Kropatsch
Regina
R
Department of Human Genetics, Ruhr University, Universitätsstrasse 150, 44801 Bochum, Germany. regina.kropatsch@rub.de
Petrasch-Parwez
Elisabeth
E
Seelow
Dominik
D
Schlichting
Annegrit
A
Gerding
Wanda M
WM
Akkad
Denis A
DA
Epplen
Joerg T
JT
Dekomien
Gabriele
G
D051722:ADAM Proteins / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D004283:Dog Diseases / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D004285:Dogs; D017353:Gene Deletion; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007494:Ireland; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D016133:Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000662:veterinary*
D018076:DNA, Complementary; D051722:ADAM Proteins