Mapping of X-linked Progressive Retinal Atrophy (XLPRA), the Canine Homolog of Retinitis Pigmentosa 3 (RP3
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Title |
Mapping of X-linked Progressive Retinal Atrophy (XLPRA), the Canine Homolog of Retinitis Pigmentosa 3 (RP3
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Creator |
Zeiss, Caroline J
Ray, Kunal Acland, Gregory M Aguirre, Gustavo D |
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Subject |
Molecular & Human Genetics
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Description |
X-linked progressive retinal atrophy (XLPRA) in the Siberian husky dog is a naturally occurring X-linked retinopathy closely resembling X-linked retinitis pigmentosa (XLRP) in humans. In affected males, initial degeneration of rods is followed by cone degeneration and complete retinal atrophy; carrier females have random patches of rod degeneration consistent with random X chromosome inactivation. By typing the XLPRA pedigree with five intragenic markers [dystrophin, retinitis pigmentosa GTPase regulator (RPGR), tissue inhibitor of metalloproteinases 1, androgen receptor and factor IX], we established a linkage map of the canine X chromosome, and confirmed that the order of these five genes is identical to that on the human X. XLPRA was tightly linked to an intragenic RPGR polymorphism (LOD 11.7, zero recombination), thus confirming locus homology with RP3. We cloned the full-length canine RPGR cDNA and three additional splice variants. No disease-causing mutation was found in the RPGR-coding sequence of the four splice variants characterized, a finding similar to ~80% of human XLRP patients whose disease maps to the RP3 locus. In addition, there were no significant differences in the proportional expression of each splice variant in normal and pre-degenerate XLPRA-affected retina. Expression of all RPGR splice variants increased later in the disease, when retinas were undergoing active degeneration. The results provide further evidence of cross-species retention of a complex splicing pattern in the 3′ portion of RPGR, the functional significance of which is unknown. In addition, the possibility of another disease locus in the RP3 region is supported. cAROLINE
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Date |
2000
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://www.eprints.iicb.res.in/835/1/HUMAN_MOLECULAR_GENETICS__9(_4)_531%2D537;2000[52].pdf
Zeiss, Caroline J and Ray, Kunal and Acland, Gregory M and Aguirre, Gustavo D (2000) Mapping of X-linked Progressive Retinal Atrophy (XLPRA), the Canine Homolog of Retinitis Pigmentosa 3 (RP3. Human Molecular Genetics , 9 (4). pp. 531-537. |
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Relation |
http://dx.doi.org/ 10.1093/hmg/9.4.531
http://www.eprints.iicb.res.in/835/ |
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