Identical mutation in a novel retinal gene causes progressive rod–cone degeneration in dogs and retinitis pigmentosa in humans

Barbara Zangerl; Orly Goldstein; Alisdair R Philp; Sarah J.P Lindauer; Susan E Pearce-Kelling; Robert F Mullins; Alexander S Graphodatsky; Daniel Ripoll; Jeanette S Felix; Edwin M Stone; Gregory M Acland; Gustavo D Aguirre

doi:10.1016/j.ygeno.2006.07.007

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Identical mutation in a novel retinal gene causes progressive rod–cone degeneration in dogs and retinitis pigmentosa in humans

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Identical mutation in a novel retinal gene causes progressive rod–cone degeneration in dogs and retinitis pigmentosa in humans

Barbara Zangerl, Orly Goldstein, Alisdair R Philp, Sarah J.P Lindauer, Susan E Pearce-Kelling, Robert F Mullins, Alexander S Graphodatsky, Daniel Ripoll, Jeanette S Felix, Edwin M Stone, …

Genomics, Vol.88(5), pp.551-563

11/2006

DOI: 10.1016/j.ygeno.2006.07.007

PMID: 16938425

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Abstract

Progressive rod–cone degeneration (prcd) is a late-onset, autosomal recessive photoreceptor degeneration of dogs and a homolog for some forms of human retinitis pigmentosa (RP). Previously, the disease-relevant interval was reduced to a 106-kb region on CFA9, and a common phenotype-specific haplotype was identified in all affected dogs from several different breeds and breed varieties. Screening of a canine retinal EST library identified partial cDNAs for novel candidate genes in the disease-relevant interval. The complete cDNA of one of these, PRCD, was cloned in dog, human, and mouse. The gene codes for a 54-amino-acid (aa) protein in dog and human and a 53-aa protein in the mouse; the first 24 aa, coded for by exon 1, are highly conserved in 14 vertebrate species. A homozygous mutation (TGC → TAC) in the second codon shows complete concordance with the disorder in 18 different dog breeds/breed varieties tested. The same homozygous mutation was identified in a human patient from Bangladesh with autosomal recessive RP. Expression studies support the predominant expression of this gene in the retina, with equal expression in the retinal pigment epithelium, photoreceptor, and ganglion cell layers. This study provides strong evidence that a mutation in the novel gene PRCD is the cause of autosomal recessive retinal degeneration in both dogs and humans.

Genetic Markers

Retinitis Pigmentosa

Mutation

Genetic predisposition to disease

Genetic variation

Dogs

Genetic linkage

Retinal degeneration

Genetic diversity

Disease models, animal

Details

Title: Subtitle: Identical mutation in a novel retinal gene causes progressive rod–cone degeneration in dogs and retinitis pigmentosa in humans
Creators: Barbara Zangerl - Clinical Studies–Philadelphia, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Orly Goldstein - James A. Baker Institute, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
Alisdair R Philp - Ophthalmology and Visual Sciences, Carver College of Medicine at The University of Iowa, Iowa City, IA 52242, USA
Sarah J.P Lindauer - Clinical Studies–Philadelphia, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Susan E Pearce-Kelling - James A. Baker Institute, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
Robert F Mullins - Ophthalmology and Visual Sciences, Carver College of Medicine at The University of Iowa, Iowa City, IA 52242, USA
Alexander S Graphodatsky - Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, Russian Federation
Daniel Ripoll - Computational Biology Service Unit, Cornell Theory Center, Cornell University, Ithaca, NY 14853, USA
Jeanette S Felix
Edwin M Stone - Ophthalmology and Visual Sciences, Carver College of Medicine at The University of Iowa, Iowa City, IA 52242, USA
Gregory M Acland - James A. Baker Institute, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
Gustavo D Aguirre - Clinical Studies–Philadelphia, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Resource Type: Journal article
Publication Details: Genomics, Vol.88(5), pp.551-563
DOI: 10.1016/j.ygeno.2006.07.007
PMID: 16938425
NLM abbreviation: Genomics
ISSN: 0888-7543
eISSN: 1089-8646
Publisher: Elsevier Inc
Language: English
Date published: 11/2006
Academic Unit: Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983979987502771

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