| Title |
Genome-wide association study in RPGRIP1−/− dogs identifies a modifier locus that determines the onset of retinal degeneration
|
|---|---|
| Published in |
Mammalian Genome, December 2011
|
| DOI | 10.1007/s00335-011-9384-9 |
| Pubmed ID | |
| Authors |
Keiko Miyadera, Kumiko Kato, Mike Boursnell, Cathryn S. Mellersh, David R. Sargan |
| Abstract |
Cone-rod dystrophy (CRD) is a form of inherited retinal degeneration (RD) causing blindness in man as well as in several breeds of dog. Previously, a 44 bp insertion in RPGRIP1 (retinitis pigmentosa GTPase regulator interacting protein-1) was associated with a recessive early-onset CRD (cone-rod dystrophy 1, cord1) in a Miniature longhaired dachshund (MLHD) research colony. Yet in the MLHD pet population, extensive range of the onset age has been observed among RD cases, with some RPGRIP1(-/-) dogs lacking obvious clinical signs. Phenotypic variation has been known in human homologous diseases, including retinitis pigmentosa and Leber congenital amaurosis, indicating possible involvement of modifiers. To explore additional genetic loci associated with the phenotypic variation observed in MLHDs, a genome-wide association study was carried out using Canine SNP20 arrays in 83 RPGRIP1(-/-) MLHDs with variable ages of onset or no clinical abnormality. Using these samples, comparison of 31 early-onset RD cases against 49 controls (15 late-onset RD and 34 normal dogs combined) identified a strong association (P = 5.05 × 10(-13)) at a single locus on canine chromosome 15. At this locus, the majority of early-onset RD cases but few of the controls were homozygous for a 1.49 Mb interval containing ~11 genes. We conclude that homozygosity at both RPGRIP1 and the newly mapped second locus is necessary to develop early-onset RD, whereas RPGRIP1(-/-) alone leads to late-onset RD or no apparent clinical phenotype. This study establishes a unique model of canine RD requiring homozygous mutations at two distinct genetic loci for the manifestation of early-onset RD. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Australia | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 37 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Other | 6 | 16% |
| Student > Ph. D. Student | 6 | 16% |
| Researcher | 6 | 16% |
| Student > Postgraduate | 5 | 14% |
| Student > Bachelor | 4 | 11% |
| Other | 5 | 14% |
| Unknown | 5 | 14% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 12 | 32% |
| Veterinary Science and Veterinary Medicine | 8 | 22% |
| Biochemistry, Genetics and Molecular Biology | 6 | 16% |
| Medicine and Dentistry | 4 | 11% |
| Computer Science | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 5 | 14% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 December 2011.
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#18,303,139
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Outputs from Mammalian Genome
#1,002
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#195,527
of 243,183 outputs
Outputs of similar age from Mammalian Genome
#12
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