Abstract
In a project begun more than 15 years ago we used linkage mapping and positional candidate gene cloning to identify two genes causing autosomal dominant retinitis pigmentosa (adRP). The genes are RP I, which maps to chromosome 8q12.1, and RP10 (IMPDH 1), which maps to 7g32.1. Although different families and different regions of the genome are involved, the studies were done in parallel because the methods used, and the underlying genetic concepts, are identical. Now that the genes have been identified, though, the functional properties of the two proteins are strikingly different, so divergent approaches are required to better understand the pathophysiology of mutations in each gene. This report is a summary of our current understanding of these two genes, contrastingthe similar approaches to identifying the genes and mutations with the dissimilar strategies for functional analysis. In microcosm, this serves as a reminder that retinal disease genes associated with similar clinical phenotypes may have very different biological roles.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Berson, E. L., Grimsby, J. L., Adams, S. M., McGee, T. L., Sweklo, E., Pierce, E. A., Sandberg,M. A., and Dryja, T. P., 2002, Clinical features and mutations in patients with dominant retinitis pigmentosa-1 (RPI)Invest. Ophthalmol. Vis. Sci.42,2217–2224.
Blackshaw, S., Fraioli, R. E., Furukawa, T., and Cepko, C. L., 2001, Comprehensive analysis of photoreceptor gene expression and the identification of candidate retinal disease genesCell107,579–589.
Blanton, S. H., Heckenlively, J. R., Cottingham, A. W., Friedman, J., Sadler, L. A., Wagner, W., Friedman, L. H., and Daiger, S. D., 1991, Linkage mapping of autosomal dominant retinitis pigmentosa (RPI) to the pericentric region of human chromosome 8Genomics11,857–869.
Bowne, S. J., Daiger, S. P., Hims, M. M., Sohocki, M. M., Malone, K. A., McKie, A. B., Heckenlively, J. R., Birch, D. G., Inglehearn, C. F., Bhattacharya, S. S., Bird, A., and Sullivan, L. S., 1999, Mutations in the RP1 gene causing autosomal dominant retinitis pigmentosaHum. Mol. Genet.11:2121–2128.
Bowne, S. J., Sullivan, L. S., Blanton, S. H., Cepko, C. L., Blackshaw, S., Birch, D. G., Hughbanks-Wheaton, D., Heckenlively, J. R., and Daiger, S. P., 2002, Mutations in the inosine monophosphatedehydrogenase I gene (IMPDH1) cause the RP 10 form of autosomal dominant retinitis pigmentosaHum. Mol.Genet.11,559–568.
Dietrich, K., Jacobi, F. K., Tippmann, S., Schmid, R., Zrenner, E., Wissinger, B., and Apfelstedt-Sylla, E., 2002, A novel mutation of the RP1 gene (Lys778ter) associated with autosomal dominant retinitis pigmentosaBrit. J. Ophthalmol.86,328–332.
Field, L. L., Heckenlively, J. R., Sparks, R. S., Garcia, C. A., Farson, C., Zedalis, D., Sparkes, M. C., Crist, M., Tideman, S., and Spence, M. A., 1982, Linkage analysis of five pedigrees affected with typical autosomal dominant retinitis pigmentosaJ.Med.Genet.19,266–270.
Gao, J., Cheon, K., Nusinowitz, S., Liu, Q., Bei, D., Atkins, K., Azimi, A., Daiger, S. P., Farber, D. B., Heckenlively, J. R., Pierce, E. A., Sullivan, L. S., and Zuo, J., 2002, Progressive photoreceptor degeneration, outer segment dysplasia and rhodopsin mis-localization in mice with targeted disruption of the retinitis pigmentosa-1(Rpl)gene,Proc. Nat. Acad. Sci. USA.99,5698–5703.
Gu, J. J, Spychala, J., and Mitchell, B. S., 1997, Regulation of the human inosine monophosphate dehydrogenase type I gene. Utilization of alternative promotersJ. Biol. Chem.272,4458–466.
Guillonneau, X., Piriev, N. I., Danciger, M., Kozak, C. A., Cideciyan, A. V., Jacobson, S. G., and Farber, D. B., 1999, A nonsense mutation in a novel gene is associated with retinitis pigmentosa in a family linked to the RP1 locusHum. Mol. Genet.8,1541–1546.
Inglehearn, C. F., McHale, J. C., Keen, T. J., Skirton, H., and Lunt, P. W., 1999, A New family linked to the RP1 dominant retinitis pigmentosa locus on chromosome 8qJ. Med. Genet.36,646–648.
Jordan, S. A., Farrar, G. J., Kenna, P., Humphries, M. M., Sheils, D. M., Kumar-Singh, R., Sharp, E. M., Ayuso, C., Benitez, J., and Humphries, P., 1993, Localization of an autosomal dominant retinitis pigmentosa gene to chromosome 7qNat. Genet.4,54–58.
Kennan, A., Aherne, A., Palfi, A., Humphries, M., McKee„ A. Stitt, A., Simpson, D. A. C., Demtroder, K., Orntoft, T., Ayuso, C., Kenna, P. F., Farrar, G. J., and Humphries, P., 2002, Identification of an IMPDH1 mutation in autosomal dominant retinitis pigmentosa (RP10) revealed following comparative microarray analysis of transcripts derived from retinas of wild-type and Rho-/- miceHum. Mol. Genet.11,547–557.
Kerr, K. M. and Hedstrom, L., 1997, The roles of conserved carboxylate residues in IMP dehydrogenase and identification of a transition state analogBiochem.36 13365–13373.
Liu, Q., Zhou, J., Daiger, S.P., Farber, D. B., Heckenlively, J. R., Smith, J. E., Sullivan, L. S., Zuo, J., Milam, A. H., and Pierce, E. A., 2002, Identification and subcellular localization of the RPI protein in human and mouse photoreceptorsInvest. Ophthalmol. Vis. Sci.43,22–32.
McGuire, R. E., Gannon, A. M., Sadler-Sullivan, L. A., Rodriguez, J. A., and Daiger, S. P., 1995, Evidence for a major gene (RP10) for autosomal dominant retinitis pigmentosa on chromosome 7q: linkage mapping in a second, unrelated familyHum. Genet.95,71–74.
McGuire, R. E., Jordan, S. A., Braden, V. V., Bouffard, G. G., Humphries, P., Green, E. D., and Daiger, S. P., 1996, Mapping the RP10 locus for autosomal dominant retinitis pigmentosa on 7q: refined genetic positioning and localization within a well-defined YAC contigGenome Res.6,255–266.
Millán, J. M., Martinez, F., Vilela, C., Beneyto, M., Prieto, F., and Nájera, C., 1995, An autosomal dominant retinitis pigmentosa family with close linkage to D7S480 on 7qHum. Genet.96,216–218.
Mohamed, Z., Bell, C., Hammer, H. M., Converse, C. A., Esakowitz, L., and Haites, N. E., 1996, Linkage of a medium sized Scottish autosomal dominant retinitis pigmentosa family to chromosome 7qJ. Med. Genet.33,714–715.
Payne, A., Vithana, E., Khaliq, S., Hameed, A., Deller, J., Abu-Safieh, L., Kermani, S., Leroy, B. P., Mehdi, S. Q., Moore, A. T., Bird, A. C., and Bhattacharya, S. S., 2000,RPI protein truncating mutations predominate at the RP I adRP locusInvest. Ophthalmol. Vis. Sci.41,4069–4073.
Pierce, E. A., Quinn, T., Meehan, T., McGee, T. L., Berson, E. L., and Dryja, T. P., 1999, Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosaNat. Genet.22,248–254.
Sullivan, L. S., Heckenlively, J. R., Bowne, S. J., Zuo, J., Hide, W. A., Gal, A., Denton, M., Ingleheam, C. F., Blanton, S. H., and Daiger, S. P., 1999, Mutations in a novel retina-specific gene cause autosomal dominant retinitis pigmentosaNat. Genet.22,255–259.
Xu, S. - Y., Denton, M., Sullivan, L. S., Daiger, S. P., and Gal, A., 1996, Genetic mapping of RP1 on 8g11-q21 in an Australian family with autosomal dominant retinitis pigmentosa reduces the critical region to 4 cM between D8S601 and D8S285Hum. Genet.98,741–743.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media New York
About this paper
Cite this paper
Daiger, S.P. et al. (2003). Identification of the RP1 and RP10 (IMPDH1) Genes Causing Autosomal Dominant RP. In: LaVail, M.M., Hollyfield, J.G., Anderson, R.E. (eds) Retinal Degenerations. Advances in Experimental Medicine and Biology, vol 533. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0067-4_1
Download citation
DOI: https://doi.org/10.1007/978-1-4615-0067-4_1
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-4909-9
Online ISBN: 978-1-4615-0067-4
eBook Packages: Springer Book Archive