Generalized progressive retinal atrophy of Sloughi dogs is due to an 8-bp insertion in exon 21 of the PDE6B geneDekomien G. · Runte M. · Gödde R. · Epplen J.T.
Molecular Human Genetics, Ruhr-University, Bochum (Germany)
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We investigated the gene encoding the β subunit of cGMP phosphodiesterase (PDE6B) as a candidate for generalized progressive retinal atrophy (gPRA), an autosomal recessively transmitted eye disease in dogs. The PDE6B gene was isolated from a genomic library. Single-strand conformation polymorphism analysis revealed eight intronic variations in different subsets of the 14 dog breeds investigated. In addition, we identified an 8-bp insertion after codon 816 in certain Sloughi dogs. Analysis of PRA-affected and obligatory carrier Sloughis showed that this mutation cosegregates with disease status in a large pedigree. All other exchanges identified were not located in functionally relevant parts of the gene (e.g., in the splice signal consensus sites). In most dog breeds (Labrador retriever, Tibetan mastiff, dachshund, Tibetan terrier, miniature poodle, Australian cattle dog, cocker spaniel, collie, Saarloos wolfhound, Chesapeake Bay retriever, and Yorkshire terrier), PDE6B was excluded as a candidate gene for gPRA because heterozygous allele constellations were detected in diseased animals. Therefore, the PDE6B sequence variations did not segregate together with the mutation(s) causing gPRA. Direct and indirect DNA tests concerning gPRA can be offered now for a variety of different dog breeds.
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- Aguirre GD, Baldwin V, Weeks KM, Acland GM, Ray K: Frequency of the codon 807 mutation in the cGMP phosphodiesterase beta-subunit gene in Irish setters and other dog breeds with hereditary retinal degeneration. J Hered 90:143–147 (1999).
- Bayes M, Giordano M, Balcells S, Grinberg D, Vilageliu L, Martinez I, Ayuso C, Benitez J, Ramos-Arroyo MA, Chivelet P, Solans T, Valverde D, Amselem S, Goossens M, Baiget M, Gonzalez-Duarte R, Besmond C: Homozygous tandem duplication within the gene encoding the beta-subunit of rod phosphodiesterase as a cause for autosomal recessive retinitis pigmentosa. Hum Mutat 5:228–234 (1995).
Bennett N, Clerc A: cGMP phosphodiesterase dependent light-induced scattering changes in suspensions of retinal disc membranes. Biochem 31: 1858–1866 (1992).
- Church GM, Gilbert W: Genomic sequencing. Proc natl Acad Sci, USA 81:1991–1995 (1984).
- Danciger M, Blaney J, Gao YQ, Zhao DY, Heckenlively JR, Jacobson SG, Farber DB: Mutations in the PDE6B gene in autosomal recessive retinitis pigmentosa. Genomics 30:1–7 (1995).
- Dekomien G, Epplen JT: Exclusion of the PDE6A gene for generalised progressive retinal atrophy in 11 breeds of dogs. Anim Genet 31:135–139 (2000).
Dekomien G, Klein W, Epplen JT: Polymorphisms in the canine rod transducin gene and exclusion as cause for generalised progressive retinal atrophy (gPRA). J exp anim Sci 39:86–90 (1998).
- Dryja TP, Li T: Molecular genetics of retinitis pigmentosa. Hum molec Genet 4:1739–1743 (1995).
- Farber DB: From mice to men: the cyclic GMP phosphodiesterase gene in vision and disease. Invest Ophthalmol vis Sci 36:263–375 (1995).
Farrar GJ, Jordan SA, Kumar-Singh R, Inglehearn CF, Gal A, Greggory C: Extensive genetic heterogeneity in autosomal dominant retinitis pigmentosa, in Hollyfield JG, Anderson RE, LaVail MM (eds): Retinal Degeneration, pp 63–77 (Plenum Press, New York 1993).
- Jäckel S, Epplen JT, Kauth M, Miterski B, Tschentscher F, Epplen C: PCR-SSCP or how to detect reliably and efficiently each sequence variation in many samples and many genes. Electrophoresis 19:3055–3061 (1998).
- Kajiwara K, Berson EL, Dryja TP: Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci. Science 264:1604–1607 (1994).
- Mansergh FC, Millington-Ward S, Kennan A, Kiang AS, Humphries M, Farrar GJ, Humphries P, Kenna PF: Retinitis pigmentosa and progressive sensorineural hearing loss caused by a C12258A mutation in the mitochondrial MTTS2 gene. Am J hum Genet 64:971–985 (1999).
- McLaughlin ME, Ehrhard TL, Berson EL, Dryja TP: Recessive mutations in the gene encoding the beta-subunit of rod phosphodiesterase in patients with retinitis pigmentosa. Nature Genet 4:130–134 (1993).
- Petersen-Jones SM, Entz DD, Sargan DR: cGMP phosphodiesterase-α mutation causes progressive retinal atrophy in the Cardigan Welsh corgi dog. Invest Ophthalmol vis Sci 40:1637–1644 (1999).
Pittler SJ, Baehr W: Identification of a nonsense mutation in the rod photoreceptor cGMP phosphodiesterase β subunit gene of the rd mouse. Proc natl Acad Sci, USA 90:8322–8326 (1991).
- Ray K, Baldwin V, Acland GM, Blanton SH, Aguirre GD: Cosegregation of codon 807 mutation of canine rod cGMP phosphodiesterase β gene and rcd1. Invest Ophthalmol vis Sci 35:4291–4299 (1994).
- Runte M, Dekomien G, Epplen JT: Evaluation of RDS/peripherin and ROM1 as candidate genes in generalised progressive retinal atrophy and exclusion of digenic inheritance. Anim Genet 31:223–227 (2000).
Sambrook J, Fritsch EF, Maniatis T: Molecular Cloning: A Laboratory Manual, 2nd Ed (Cold Spring Harbor Laboratory Press, Cold Spring Harbor 1989).
- Sharp PA: Speculations on RNA splicing. Cell 23:643–646 (1981).
- Shastry BS: Signal transduction in the retina and inherited retinopathies. Cell molec Life Sci 53:419–429 (1997).
- Suber ML, Pittler SJ, Qin N, Wright GC, Holcombe V, Lee RH, Craft CM, Lolley RN, Baehr W: Irish setter dogs affected with rod/cone dysplasia contain a nonsense mutation in the rod cGMP phosphodiesterase beta-subunit gene. Proc natl Acad Sci, USA 90:3968–3972 (1993).
Stryer L: Vision: from photon to perception. Proc natl Acad Sci, USA 93:557–559 (1996).
- Weber B, Riess O, Hutchinson G, Collins C, Lin BY, Kowbel D, Andrew S, Schappert K, Hayden MR: Genomic organisation and complete sequence of the human gene encoding the beta-subunit of the cGMP phosphodiesterase and its localisation to 4p16.6. Nucl Acids Res 19:6263–6268 (1991).
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