Abstract
In recent years the field of retinal gene discovery has experienced an explosion. An estimated 10,000-30,000 genes are thought to be expressed in the human retina (Shimizu-Matsumoto et al., 1997), with nearly 5,000 retinal transcripts catalogued from expressed sequence tag (EST) datasets (Bortoluzzi et al., 2000) and over 26,000 different transcripts represented in retina serial analysis of gene expression (SAGE) libraries (Sharon et al, 2002). A wide variety of methods have been developed and utilized to define novel retinal genes, particularly in an effort to identify genes targeted in human retinopathies. To date there are 144 diseases of the retina described that have been mapped to human chromosomal locations, and an additional 41 human disorders involving some form of retinal dystrophy for which the genetic map locations have yet to be determined (RetNet Retinal Information Networkhttp://www.sph.uth.tmc.edu/retnet/;Online Mendelian Inheritance in Man (OMIM)http://www.ncbi.nlm.nih.gov/omim/). Despite recent efforts to discover novel genes by analyzing increasingly greater volumes of information arising from human genomic sequence data organization and expression studies, the disease genes for less than one-half of these conditions have at present been cloned. While some of these disorders may be attributed to allelic heterogeneity, a significant number of genes that account for retinal degenerative phenotypes remain to be defined.
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References
Allikmets, R., Singh, N., Sun, H., Shroyer, N.F., Hutchinson, A., Chidambaram, A., Gerrard, B., Baird, L., Stauffer, D., Peiffer, A., Rattner, A., Smallwood, P., Li, Y., Anderson, K.L., Lewis, R.A., Nathans, J., Leppert, M., Dean, M., and Lupski, J.R., 1997, A photoreceptor cell-specific ATP-binding transporter gene(ABCR)is mutated in recessive Stargardt macular dystrophy.Nat. Genet.15:236–46.
Becker, K.G., Simon, R.M., Bailey-Wilson, J.E., Freidlin, B., Biddison, W.E., McFarland, H.F., and Trent, J.M., 1998, Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases.Proc. Natl. Acad. Sci. U.S.A.95:9979–84.
Berger, W., Meindl, A., van de Pol, T.J., Cremers, F.P., Ropers, H.H., Doerner, C., Monaco, A., Bergen, A.A., Lebo, R., Warburg, M., Zergollem, L., Lorenz, B., Gal, A., Bleeker-Wagemakers, E.M., and Meitinger, T., 1992, Isolation of a candidate gene for Norrie disease by positional cloning.Nat. Genet.1:199–203.
Bernstein, S.L., Borst, D.E., and Wong, P.W., 1995, Isolation of differentially expressed human fovea genes: candidates for macular disease.Mol. Vis. 1:4.
Bernstein, S.L., Borst, D.E., Neuder, M.E., and Wong, P., 1996, Characterization of a human fovea cDNA library and regional differential gene expression in the human retina.Genomics32:301–8.
Bernstein, S.L., Borst, D.E., and Wong, P., 1997, Region specific mitochondrial gene expression in the human retina.Brain Res.744:143–6.
Bernstein, P.S., Tammur, J., Singh, N., Hutchinson, A., Dixon, M., Pappas, C.M., Zabriskie, N.A., Zhang, K., Petrukhin, K., Leppert, M., and Allikmets, R., 2001, Diverse macular dystrophy phenotype caused by a novel complex mutation in theELOVL4gene.Invest. Ophthalmol. Vis. Sci.42:3331–6.
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 genes.Ce!!107:579–89.
Bortoluzzi, S., d’Alessi, F., and Danieli, G.A., 2000, A novel resource for the study of genes expressed in the adult human retina.Invest. Ophthalmol. Vis. Sci.41:3305–8.
Chen, Z.Y., Hendriks, R.W., Jobling, M.A., Powell, J.F., Breakefield, X.O., Sims, K.B., and Craig, I.W., 1992, Isolation and characterization of a candidate gene for Norrie disease.Nat. Genet.1:204–8.
Cinti, D.L., Cook, L., Nagi, M.N., and Suneja, S.K., 1992, The fatty acid chain elongation system of mammalian endoplasmic reticulum.Prog. Lipid Res.31:1–51.
Cremers, F.P., van de Pol, D.J., van Kerkhoff, L.P., Wieringa, B., and Ropers, H.H., 1990, Cloning of a gene that is rearranged in patients with choroideraemia.Nature347:674–7.
Dharmaraj, S., Li, Y., Robitaille, J.M., Silva, E., Zhu, D., Mitchell, T.N., Maltby, L.P., Baffoe-Bonnie, A.B., and Maumenee, I.H., 2000, A novel locus for Leber congenital amaurosis maps to chromosome 6q.Am. J. Hum. Genet.66:319–26.
Edwards, A.O., Donoso, L.A., and Ritter, R., 3rd., 2001, A novel gene for autosomal dominant Stargardt-like macular dystrophy with homology to the SUR4 protein family.Invest. Ophthalmol. Vis. Sci.42:2652–63.
Gehrig, A., Felbor, U., Kelsell, R.E., Hunt, D.M., Maumenee, I.H., and Weber, B.H., 1998, Assessment of the interphotoreceptor matrix proteoglycan-1 (IMPG1) gene localised to 6q 13-q15 in autosomal dominant Stargardt-like disease (ADSTGD), progressive bifocal chorioretinal atrophy (PBCRA), and North Carolina macular dystrophy (MCDR1).J. Med. Genet.35:641–5.
Griesinger, I.B., Sieving, P.A., and Ayyagari, R., 2000, Autosomal dominant macular atrophy at 6g14 excludes CORD? and MCDR1/PBCRA loci.Invest. Ophthalmol. Vis. Sci.41:248–55.
Katsanis, N., Worley, K.C., Gonzalez, G., Ansley, S.J., and Lupski, J.R., 2002, A computational/functional genomics approach for the enrichment of the retinal transcriptome and the identification of positional candidate retinopathy genes.Proc. Nat!. Acad. Sci. U.S.A.99:14326–31.
Kelsell, R.E., Godley, B.F., Evans, K., Tiffin, P.A., Gregory, C.Y., Plant, C., Moore, A.T., Bird, A.C., and Hunt, D.M., 1995, Localization of the gene for progressive bifocal chorioretinal atrophy (PBCRA) to chromosome 6q.Hum. Mol. Genet.4:1653–6.
Kelsell, R.E., Gregory-Evans, K., Gregory-Evans, C.Y., Holder, G.E., Jay, M.R., Weber, B.H., Moore, A.T., Bird, A.C., and Hunt, D.M., 1998, Localization of a gene (CORD7) for a dominant cone-rod dystrophy to chromosome 6q.Am. J. Hum. Genet.63:274–9.
Kniazeva, M.F., Chiang, M.F., Cutting, G.R., Zack, D.J., Han, M., and Zhang, K., 1999, Clinical and genetic studies of an autosomal dominant cone-rod dystrophy with features of Stargardt disease.Ophthalmic Genet.20:71–81.
Kniazeva, M., Traboulsi, E.I., Yu, Z., Stefko, S.T., Gorin, M.B., Shugart, Y.Y., O’Connell, J.R., Blaschak, Cutting, G., Han, M., and Zhang, K., 2000, A new locus for dominant drusen and macular degeneration maps to chromosome 6q14.Am. J. Ophthalmol.130:197–202.
Lagali, P.S., MacDonald, I.M., Griesinger, I.B., Chambers, M.L., Ayyagari, R., and Wong, P.W., 2000, Autosomal dominant Stargardt-like macular dystrophy segregating in a large Canadian family.Can. J. Ophthalmol.35:315–24.
Lagali, P.S., Kakuk, L.E., Griesinger, I.B., Wong, P.W., and Ayyagari, R., 2002, Identification and characterization ofC6orf37, a novel candidate human retinal disease gene on chromosome 6q14.Biochem. Biophys. Res. Commun.293:356–65.
Lagali, P.S., Liu, J., Ambasudhan, R., Kakuk, L.E., Bernstein, S.L., Seigel, G.M., Wong, P.W., and Ayyagari, R., 2003, Evolutionarily conservedELOVL4gene expression in the vertebrate retinaInvest. Ophthalmol. Vis. Sci.(in press).
Malone, K., Sohocki, M.M., Sullivan, L.S., and Daiger, S.P., 1999, Identifying and mapping novel retinal expressed ESTs from humans.Mol. Vis.5:5.
Meindl, A., Dry, K., Herrmann, K., Manson, F., Ciccodicola, A., Edgar, A., Carvalho, M.R., Achatz, H., Hellebrand, H., Lennon, A., Migliaccio, C., Porter, K., Zrenner, E., Bird, A., Jay, M., Lorenz, B., Wittwer, B., D’Urso, M., Meitinger, T., and Wright; A., 1996, A gene(RPGR)with homology to the RCC 1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3).Nat. Genet.13:35–42.
Oh, C.S., Toke, D.A., Mandala, S., and Martin, C.E., 1997ELO2andELO3, homologues of theSaccharomyces cerevisiae ELOIgene, function in fatty acid elongation and are required for sphingolipid formation.J. Biol. Chem.272:17376–84.
Petrukhin, K., Koisti, M.J., Bakall, B., Li, W., Xie, G., Marknell, T., Sandgren, O., Forsman, K., Holmgren, G., Andreasson, S., Vujic, M., Bergen, A.A., McGarty-Dugan, V., Figueroa, D., Austin, C.P., Metzker, M.L., Caskey, C.T., and Wadelius, C., 1998, Identification of the gene responsible for Best macular dystrophy.Nat. Genet.19:241–7.
Roepman, R., van Duijnhoven, G., Rosenberg, T., Pinckers, A.J., Bleeker-Wagemakers, L.M., Bergen, A.A., Post, J., Beck, A., Reinhardt, R., Ropers, H.H., Cremers, F.P., and Berger, W., 1996, Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC4.Hum. Mol. Genet.5:1035–41.
Khaliq, S., Hameed, A., Ismail, M., Mehdi, S.Q., Bessant, D.A., Payne, A.M., and Bhattacharya, S.S., 1999, Refinement of the locus for autosomal recessive Retinitis pigmentosa (RP25) linked to chromosome 6q in a family of Pakistani origin.Am. J. Hum. Genet.65:571–4.
Sauer, C.G., Schworm, H.D., Ulbig, M., Blankenagel, A., Rohrschneider, K., Pauleikhoff, D., Grimm, T., and Weber, B.H., 1997, An ancestral core haplotype defines the critical region harbouring the North Carolina macular dystrophy gene (MCDRI).J. Med. Genet.34:961–6.
Schoen, T.J., Mazuruk, K., Chader, G.J., and Rodriguez, I.R., 1995, Isolation of candidate genes for macular degeneration using an improved solid-phase subtractive cloning technique.Biochem. Biophys. Res. Commun.213:181–8.
Schwahn, U., Lenzner, S., Dong, J., Feil, S., Hinzmann, B., van Duijnhoven, G., Kirschner, R., Hemberger, M., Bergen, A.A., Rosenberg, T., Pinckers, A.J., Fundele, R., Rosenthal, A., Cremers, F.P., Ropers, H.H., and Berger, W., 1998, Positional cloning of the gene for X-linked retinitis pigmentosa 2.Nat. Genet.19:32732.
Sharon, D., Blackshaw, S., Cepko, C.L., and Dryja, T.P., 2002, Profile of the genes expressed in the human peripheral retina, macula, and retinal pigment epithelium determined through serial analysis of gene expression (SAGE).Proc. Natl. Acad. Sci. U.S.A.99:315–20.
Shimizu-Matsumoto, A., Adachi, W., Mizuno, K., Inazawa, J., Nishida, K., Kinoshita, S., Matsubara, K., and Okubo, K., 1997, An expression profile of genes in human retina and isolation of a complementary DNA for a novel rod photoreceptor protein.Invest. Ophthalmol. Vis. Sci.38:2576–85.
Sinha, S., Sharma, A., Agarwal, N., Swaroop, A., and Yang-Feng, T.L., 2000, Expression profile and chromosomal location of cDNA clones, identified from an enriched adult retina library.Invest. Ophthalmol. Vis. Sci.41:24–8.
Sohocki, M.M., Malone, K.A., Sullivan, L.S., and Daiger, S.P., 1999, Localization of retina/pineal-expressed sequences: identification of novel candidate genes for inherited retinal disorders.Genomics58:29–33.
Stohr, H., Mah, N., Schulz, H.I,., Gehrig, A., Frohlich, S., and Weber, B.H., 2000, EST mining of the UniGene dataset to identify retina-specific genes.Cytogenet. Cell. Genet.91:267–77.
Stone, E.M., Nichols, B.E., Kimura, A.E., Weingeist, T.A., Drack, A., and Sheffield, V.C., 1994, Clinical features of a Stargardt-like dominant progressive macular dystrophy with genetic linkage to chromosome 6q.Arch. Ophthalmol.112:765–72.
Toke, D.A. and Martin, C.E., 1996, Isolation and characterization of a gene affecting fatty acid elongation inSaccharomyces cerevisiae. J Biol. Chem.271:18413–22.
Yoshida, S., Yashar, B.M., Hiriyanna, S., and Swaroop, A., 2002, Microarray analysis of gene expression in the aging human retina.Invest. Ophthalmol. Vis. Sci.43:2554–60.
Zhang, K., Kniazeva, M., Han, M., Li, W., Yu, Z., Yang, Z., Li, Y., Metzker, M.L., Allikmets, R., Zack, D.J., Kakuk, L.E., Lagali, P.S., Wong, P.W., MacDonald, I.M., Sieving, P.A., Figueroa, D.J., Austin, C.P., Gould, R.J., Ayyagari, R., and Petrukhin, K., 2001, A 5-bp deletion inELOVL4is associated with two related forms of autosomal dominant macular dystrophy.Nat. Genet. 27:89–93.
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Lagali, P.S., Ayyagari, R., Wong, P.W. (2003). An Integrated Genetic Approach to Identify Candidate Genes for Human Chromosome 6q-Linked Retinal Disorders. 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_3
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DOI: https://doi.org/10.1007/978-1-4615-0067-4_3
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