Generalized progressive retinal atrophy in the Irish Glen of Imaal Terrier is associated with a deletion in the ADAM9 gene.
Mol Cell Probes
; 24(6): 357-63, 2010 Dec.
Article
en En
| MEDLINE
| ID: mdl-20691256
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Degeneración Retiniana
/
Eliminación de Gen
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Predisposición Genética a la Enfermedad
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Enfermedades de los Perros
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Proteínas ADAM
/
Estudios de Asociación Genética
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
País/Región como asunto:
Europa
Idioma:
En
Revista:
Mol Cell Probes
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOTECNOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Alemania