Genetic architecture of retinal and macular degenerative diseases: The promise and challenges of next-generation sequencing

Genome Medicine

Volumn 5, Issue 9, 2013, Pages

  Ratnapriya, Rinki ^a   Swaroop, Anand ^a  

^a NATIONAL EYE INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BARDET BIEDL SYNDROME; CHROMATIN IMMUNOPRECIPITATION; COMPLEMENT SYSTEM; COPY NUMBER VARIATION; DIABETIC RETINOPATHY; DNA SEQUENCE; EXOME; GENE IDENTIFICATION; GENE MUTATION; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC VARIABILITY; HIGH MYOPIA; HIGH THROUGHPUT SEQUENCING; HUMAN; HYPOPITUITARISM; INDEL MUTATION; LEBER CONGENITAL AMAUROSIS; NEXT GENERATION SEQUENCING; NIGHT BLINDNESS; NONHUMAN; OPEN ANGLE GLAUCOMA; PERIPHERAL VISION; PHOTORECEPTOR; PRIORITY JOURNAL; RETINA DEGENERATION; RETINA MACULA AGE RELATED DEGENERATION; RETINA MACULA DEGENERATION; RETINITIS PIGMENTOSA; REVIEW; RNA SEQUENCE; SERIAL ANALYSIS OF GENE EXPRESSION; SINGLE NUCLEOTIDE POLYMORPHISM; USHER SYNDROME; VISION; VISUAL IMPAIRMENT;

EID: 84885775437     PISSN: None     EISSN: 1756994X     Source Type: Journal    
DOI: 10.1186/gm488     Document Type: Review

References (136)

1. Dowling JE. The Retina: an Approachable Part of the Brain 1987, Cambridge, MA: Belknap Press.
2. Masland RH. The fundamental plan of the retina. Nat Neurosci 2001, 4:877-886.
3. Lamb TD, Collin SP, Pugh EN. Evolution of the vertebrate eye: opsins, photoreceptors, retina and eye cup. Nat Rev Neurosci 2007, 8:960-976.
4. Nathans J, Thomas D, Hogness DS. Molecular genetics of human color vision: the genes encoding blue, green, and red pigments. Science 1986, 232:193-202.
5. Curcio CA, Sloan KR, Kalina RE, Hendrickson AE. Human photoreceptor topography. J Comp Neurol 1990, 292:497-523.
6. Swaroop A, Kim D, Forrest D. Transcriptional regulation of photoreceptor development and homeostasis in the mammalian retina. Nat Rev Neurosci 2010, 11:563-576.
7. Bramall AN, Wright AF, Jacobson SG, McInnes RR. The genomic, biochemical, and cellular responses of the retina in inherited photoreceptor degenerations and prospects for the treatment of these disorders. Annu Rev Neurosci 2010, 33:441-472.
8. Wright AF, Chakarova CF, Abd El-Aziz MM, Bhattacharya SS. Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait. Nat Rev Genet 2010, 11:273-284.
9. RetNet [https://sph.uth.edu/retnet/].
10. Fritsche LG, Chen W, Schu M, Yaspan BL, Yu Y, Thorleifsson G, Zack DJ, Arakawa S, Cipriani V, Ripke S, Igo RP, Buitendijk GH, Sim X, Weeks DE, Guymer RH, Merriam JE, Francis PJ, Hannum G, Agarwal A, Armbrecht AM, Audo I, Aung T, Barile GR, Benchaboune M, Bird AC, Bishop PN, Branham KE, Brooks M, Brucker AJ, Cade WH, et al. Seven new loci associated with age-related macular degeneration. Nat Genet 2013, 45:433-439.
11. Thorleifsson G, Walters GB, Hewitt AW, Masson G, Helgason A, DeWan A, Sigurdsson A, Jonasdottir A, Gudjonsson SA, Magnusson KP, Stefansson H, Lam DS, Tam PO, Gudmundsdottir GJ, Southgate L, Burdon KP, Gottfredsdottir MS, Aldred MA, Mitchell P, St Clair D, Collier DA, Tang N, Sveinsson O, Macgregor S, Martin NG, Cree AJ, Gibson J, Macleod A, Jacob A, Ennis S, et al. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma. Nat Genet 2010, 42:906-909.
12. van Koolwijk LM, Ramdas WD, Ikram MK, Jansonius NM, Pasutto F, Hysi PG, Macgregor S, Janssen SF, Hewitt AW, Viswanathan AC, ten Brink JB, Hosseini SM, Amin N, Despriet DD, Willemse-Assink JJ, Kramer R, Rivadeneira F, Struchalin M, Aulchenko YS, Weisschuh N, Zenkel M, Mardin CY, Gramer E, Welge-Lüssen U, Montgomery GW, Carbonaro F, Young TL, Bellenguez C, McGuffin P, , et al. DCCT/EDIC Research Group Common genetic determinants of intraocular pressure and primary open-angle glaucoma. PLoS Genet 2012, 8:e1002611. DCCT/EDIC Research Group.
13. Wiggs JL, Yaspan BL, Hauser MA, Kang JH, Allingham RR, Olson LM, Abdrabou W, Fan BJ, Wang DY, Brodeur W, Budenz DL, Caprioli J, Crenshaw A, Crooks K, Delbono E, Doheny KF, Friedman DS, Gaasterland D, Gaasterland T, Laurie C, Lee RK, Lichter PR, Loomis S, Liu Y, Medeiros FA, McCarty C, Mirel D, Moroi SE, Musch DC, Realini A, et al. Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma. PLoS Genet 2012, 8:e1002654.
14. Grassi MA, Tikhomirov A, Ramalingam S, Below JE, Cox NJ, Nicolae DL. Genome-wide meta-analysis for severe diabetic retinopathy. Hum Mol Genet 2011, 20:2472-2481.
15. Priya RR, Chew EY, Swaroop A. Genetic studies of age-related macular degeneration: lessons, challenges, and opportunities for disease management. Ophthalmology 2012, 119:2526-2536.
16. Swaroop A, Chew EY, Rickman CB, Abecasis GR. Unraveling a multifactorial late-onset disease: from genetic susceptibility to disease mechanisms for age-related macular degeneration. Annu Rev Genomics Hum Genet 2009, 10:19-43.
17. Pacione LR, Szego MJ, Ikeda S, Nishina PM, McInnes RR. Progress toward understanding the genetic and biochemical mechanisms of inherited photoreceptor degenerations. Annu Rev Neurosci 2003, 26:657-700.
18. Berger W, Kloeckener-Gruissem B, Neidhardt J. The molecular basis of human retinal and vitreoretinal diseases. Prog Retin Eye Res 2010, 29:335-375.
19. Metzker ML. Sequencing technologies - the next generation. Nat Rev Genet 2010, 11:31-46.
20. Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson DA, Shendure J. Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet 2011, 12:745-755.
21. Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, Shaffer T, Wong M, Bhattacharjee A, Eichler EE, Bamshad M, Nickerson DA, Shendure J. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 2009, 461:272-276.
22. Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR, Zumbo P, Nayir A, Bakkaloglu A, Ozen S, Sanjad S, Nelson-Williams C, Farhi A, Mane S, Lifton RP. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci U S A 2009, 106:19096-19101.
23. Gnirke A, Melnikov A, Maguire J, Rogov P, LeProust EM, Brockman W, Fennell T, Giannoukos G, Fisher S, Russ C, Gabriel S, Jaffe DB, Lander ES, Nusbaum C. Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing. Nat Biotechnol 2009, 27:182-189.
24. Priya RR, Rajasimha HK, Brooks MJ, Swaroop A. Exome sequencing: capture and sequencing of all human coding regions for disease gene discovery. Methods Mol Biol 2012, 884:335-351.
25. CCDS database [http://www.ncbi.nlm.nih.gov/CCDS/CcdsBrowse.cgi].
26. RefSeq [http://www.ncbi.nlm.nih.gov/refseq/].
27. Zuchner S, Dallman J, Wen R, Beecham G, Naj A, Farooq A, Kohli MA, Whitehead PL, Hulme W, Konidari I, Edwards YJ, Cai G, Peter I, Seo D, Buxbaum JD, Haines JL, Blanton S, Young J, Alfonso E, Vance JM, Lam BL, Peričak-Vance MA. Whole-exome sequencing links a variant in DHDDS to retinitis pigmentosa. Am J Hum Genet 2011, 88:201-206.
28. Tucker BA, Scheetz TE, Mullins RF, DeLuca AP, Hoffmann JM, Johnston RM, Jacobson SG, Sheffield VC, Stone EM. Exome sequencing and analysis of induced pluripotent stem cells identify the cilia-related gene male germ cell-associated kinase (MAK) as a cause of retinitis pigmentosa. Proc Natl Acad Sci U S A 2011, 108:E569-E576.
29. Schrader KA, Heravi-Moussavi A, Waters PJ, Senz J, Whelan J, Ha G, Eydoux P, Nielsen T, Gallagher B, Oloumi A, Boyd N, Fernandez BA, Young TL, Jones SJ, Hirst M, Shah SP, Marra MA, Green J, Huntsman DG. Using next-generation sequencing for the diagnosis of rare disorders: a family with retinitis pigmentosa and skeletal abnormalities. J Pathol 2011, 225:12-18.
30. Abu-Safieh L, Alrashed M, Anazi S, Alkuraya H, Khan AO, Al-Owain M, Al-Zahrani J, Al-Abdi L, Hashem M, Al-Tarimi S, Sebai MA, Shamia A, Ray-Zack MD, Nassan M, Al-Hassnan ZN, Rahbeeni Z, Waheeb S, Alkharashi A, Abboud E, Al-Hazzaa SA, Alkuraya FS. Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. Genome Res 2013, 23:236-247.
31. Davidson AE, Schwarz N, Zelinger L, Stern-Schneider G, Shoemark A, Spitzbarth B, Gross M, Laxer U, Sosna J, Sergouniotis PI, Waseem NH, Wilson R, Kahn RA, Plagnol V, Wolfrum U, Banin E, Hardcastle AJ, Cheetham ME, Sharon D, Webster AR. Mutations in ARL2BP, encoding ADP-ribosylation-factor-like 2 binding protein, cause autosomal-recessive retinitis pigmentosa. Am J Hum Genet 2013, doi: 10.1016/j.ajhg.2013.06.003.
32. Perrault I, Hanein S, Zanlonghi X, Serre V, Nicouleau M, Defoort-Delhemmes S, Delphin N, Fares-Taie L, Gerber S, Xerri O, Edelson C, Goldenberg A, Duncombe A, Le Meur G, Hamel C, Silva E, Nitschke P, Calvas P, Munnich A, Roche O, Dollfus H, Kaplan J, Rozet JM. Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy. Nat Genet 2012, 44:975-977.
33. Koenekoop RK, Wang H, Majewski J, Wang X, Lopez I, Ren H, Chen Y, Li Y, Fishman GA, Genead M, Schwartzentruber J, Solanki N, Traboulsi EI, Cheng J, Logan CV, McKibbin M, Hayward BE, Parry DA, Johnson CA, Nageeb M, Poulter JA, Mohamed MD, Jafri H, Rashid Y, Taylor GR, Keser V, Mardon G, Xu H, Inglehearn CF, , et al. Finding of Rare Disease Genes (FORGE) Canada Consortium Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration. Nat Genet 2012, 44:1035-1039. Finding of Rare Disease Genes (FORGE) Canada Consortium.
34. Falk MJ, Zhang Q, Nakamaru-Ogiso E, Kannabiran C, Fonseca-Kelly Z, Chakarova C, Audo I, Mackay DS, Zeitz C, Borman AD, Staniszewska M, Shukla R, Palavalli L, Mohand-Said S, Waseem NH, Jalali S, Perin JC, Place E, Ostrovsky J, Xiao R, Bhattacharya SS, Consugar M, Webster AR, Sahel JA, Moore AT, Berson EL, Liu Q, Gai X, Pierce EA. NMNAT1 mutations cause Leber congenital amaurosis. Nat Genet 2012, 44:1040-1045.
35. Chiang PW, Wang J, Chen Y, Fu Q, Zhong J, Chen Y, Yi X, Wu R, Gan H, Shi Y, Chen Y, Barnett C, Wheaton D, Day M, Sutherland J, Heon E, Weleber RG, Gabriel LA, Cong P, Chuang K, Ye S, Sallum JM, Qi M. Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis. Nat Genet 2012, 44:972-974.
36. Sergouniotis PI, Davidson AE, Mackay DS, Li Z, Yang X, Plagnol V, Moore AT, Webster AR. Recessive mutations in KCNJ13, encoding an inwardly rectifying potassium channel subunit, cause leber congenital amaurosis. Am J Hum Genet 2011, 89:183-190.
37. Zeitz C, Jacobson SG, Hamel CP, Bujakowska K, Neuillé M, Orhan E, Zanlonghi X, Lancelot ME, Michiels C, Schwartz SB, Bocquet B, Antonio A, Audier C, Letexier M, Saraiva JP, Luu TD, Sennlaub F, Nguyen H, Poch O, Dollfus H, Lecompte O, Kohl S, Sahel JA, Bhattacharya SS, Audo I, Congenital Stationary Night Blindness Consortium Whole-exome sequencing identifies LRIT3 mutations as a cause of autosomal-recessive complete congenital stationary night blindness. Am J Hum Genet 2013, 92:67-75. Congenital Stationary Night Blindness Consortium.
38. Audo I, Bujakowska K, Orhan E, Poloschek CM, Defoort-Dhellemmes S, Drumare I, Kohl S, Luu TD, Lecompte O, Zrenner E, Lancelot ME, Antonio A, Germain A, Michiels C, Audier C, Letexier M, Saraiva JP, Leroy BP, Munier FL, Mohand-Saïd S, Lorenz B, Friedburg C, Preising M, Kellner U, Renner AB, Moskova-Doumanova V, Berger W, Wissinger B, Hamel CP, Schorderet DF, et al. Whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness. Am J Hum Genet 2012, 90:321-330.
39. Bredrup C, Saunier S, Oud MM, Fiskerstrand T, Hoischen A, Brackman D, Leh SM, Midtbø M, Filhol E, Bole-Feysot C, Nitschké P, Gilissen C, Haugen OH, Sanders JS, Stolte-Dijkstra I, Mans DA, Steenbergen EJ, Hamel BC, Matignon M, Pfundt R, Jeanpierre C, Boman H, Rødahl E, Veltman JA, Knappskog PM, Knoers NV, Roepman R, Arts HH. Ciliopathies with skeletal anomalies and renal insufficiency due to mutations in the IFT-A gene WDR19. Am J Hum Genet 2011, 89:634-643.
40. Shi Y, Li Y, Zhang D, Zhang H, Li Y, Lu F, Liu X, He F, Gong B, Cai L, Li R, Liao S, Ma S, Lin H, Cheng J, Zheng H, Shan Y, Chen B, Hu J, Jin X, Zhao P, Chen Y, Zhang Y, Lin Y, Li X, Fan Y, Yang H, Wang J, Yang Z. Exome sequencing identifies ZNF644 mutations in high myopia. PLoS Genet 2011, 7:e1002084.
41. Marion V, Stutzmann F, Gérard M, De Melo C, Schaefer E, Claussmann A, Hellé S, Delague V, Souied E, Barrey C, Verloes A, Stoetzel C, Dollfus H. Exome sequencing identifies mutations in LZTFL1, a BBSome and smoothened trafficking regulator, in a family with Bardet-Biedl syndrome with situs inversus and insertional polydactyly. J Med Genet 2012, 49:317-321.
42. Chaki M, Airik R, Ghosh AK, Giles RH, Chen R, Slaats GG, Wang H, Hurd TW, Zhou W, Cluckey A, Gee HY, Ramaswami G, Hong CJ, Hamilton BA, Cervenka I, Ganji RS, Bryja V, Arts HH, van Reeuwijk J, Oud MM, Letteboer SJ, Roepman R, Husson H, Ibraghimov-Beskrovnaya O, Yasunaga T, Walz G, Eley L, Sayer JA, Schermer B, Liebau MC, et al. Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling. Cell 2012, 150:533-548.
43. Puffenberger EG, Jinks RN, Sougnez C, Cibulskis K, Willert RA, Achilly NP, Cassidy RP, Fiorentini CJ, Heiken KF, Lawrence JJ, Mahoney MH, Miller CJ, Nair DT, Politi KA, Worcester KN, Setton RA, Dipiazza R, Sherman EA, Eastman JT, Francklyn C, Robey-Bond S, Rider NL, Gabriel S, Morton DH, Strauss KA. Genetic mapping and exome sequencing identify variants associated with five novel diseases. PLoS One 2012, 7:e28936.
44. Sergouniotis PI, Davidson AE, Mackay DS, Lenassi E, Li Z, Robson AG, Yang X, Kam JH, Isaacs TW, Holder GE, Jeffery G, Beck JA, Moore AT, Plagnol V, Webster AR. Biallelic mutations in PLA2G5, encoding group V phospholipase A2, cause benign fleck retina. Am J Hum Genet 2011, 89:782-791.
45. Roosing S, Rohrschneider K, Beryozkin A, Sharon D, Weisschuh N, Staller J, Kohl S, Zelinger L, Peters TA, Neveling K, Strom TM, van den Born LI, Hoyng CB, Klaver CC, Roepman R, Wissinger B, Banin E, Cremers FP, den Hollander AI, European Retinal Disease Consortium Mutations in RAB28, encoding a farnesylated small GTPase, are associated with autosomal-recessive cone-rod dystrophy. Am J Hum Genet 2013, 93:110-117. European Retinal Disease Consortium.
46. Aldahmesh MA, Khan AO, Mohamed JY, Alkuraya H, Ahmed H, Bobis S, Al-Mesfer S, Alkuraya FS. Identification of ADAMTS18 as a gene mutated in Knobloch syndrome. J Med Genet 2011, 48:597-601.
47. Peluso I, Conte I, Testa F, Dharmalingam G, Pizzo M, Collin RW, Meola N, Barbato S, Mutarelli M, Ziviello C, Barbarulo AM, Nigro V, Melone MA, Simonelli F, Banfi S, European Retinal Disease Consortium The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy. Orphanet J Rare Dis 2013, 8:16. European Retinal Disease Consortium.
48. Estrada-Cuzcano A, Neveling K, Kohl S, Banin E, Rotenstreich Y, Sharon D, Falik-Zaccai TC, Hipp S, Roepman R, Wissinger B, Letteboer SJ, Mans DA, Blokland EA, Kwint MP, Gijsen SJ, van Huet RA, Collin RW, Scheffer H, Veltman JA, Zrenner E, den Hollander AI, Klevering BJ, Cremers FP, European Retinal Disease Consortium Mutations in C8orf37, encoding a ciliary protein, are associated with autosomal-recessive retinal dystrophies with early macular involvement. Am J Hum Genet 2012, 90:102-109. European Retinal Disease Consortium.
49. Raychaudhuri S, Iartchouk O, Chin K, Tan PL, Tai AK, Ripke S, Gowrisankar S, Vemuri S, Montgomery K, Yu Y, Reynolds R, Zack DJ, Campochiaro B, Campochiaro P, Katsanis N, Daly MJ, Seddon JM. A rare penetrant mutation in CFH confers high risk of age-related macular degeneration. Nat Genet 2011, 43:1232-1236.
50. van de Ven JP, Nilsson SC, Tan PL, Buitendijk GH, Ristau T, Mohlin FC, Nabuurs SB, Schoenmaker-Koller FE, Smailhodzic D, Campochiaro PA, Zack DJ, Duvvari MR, Bakker B, Paun CC, Boon CJ, Uitterlinden AG, Liakopoulos S, Klevering BJ, Fauser S, Daha MR, Katsanis N, Klaver CC, Blom AM, Hoyng CB, den Hollander AI. A functional variant in the CFI gene confers a high risk of age-related macular degeneration. Nat Genet 2013, 45:813-817.
51. Eisenberger T, Slim R, Mansour A, Nauck M, Nurnberg G, Nurnberg P, Decker C, Dafinger C, Ebermann I, Bergmann C, Bolz HJ. Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3. Orphanet J Rare Dis 2012, 7:59.
52. Peachey NS, Ray TA, Florijn R, Rowe LB, Sjoerdsma T, Contreras-Alcantara S, Baba K, Tosini G, Pozdeyev N, Iuvone PM, Bojang P, Pearring JN, Simonsz HJ, van Genderen M, Birch DG, Traboulsi EI, Dorfman A, Lopez I, Ren H, Goldberg AF, Nishina PM, Lachapelle P, McCall MA, Koenekoop RK, Bergen AA, Kamermans M, Gregg RG. GPR179 is required for depolarizing bipolar cell function and is mutated in autosomal-recessive complete congenital stationary night blindness. Am J Hum Genet 2012, 90:331-339.
53. Webb TR, Parfitt DA, Gardner JC, Martinez A, Bevilacqua D, Davidson AE, Zito I, Thiselton DL, Ressa JH, Apergi M, Schwarz N, Kanuga N, Michaelides M, Cheetham ME, Gorin MB, Hardcastle AJ. Deep intronic mutation in OFD1, identified by targeted genomic next-generation sequencing, causes a severe form of X-linked retinitis pigmentosa (RP23). Hum Mol Genet 2012, 21:3647-3654.
54. Huang L, Szymanska K, Jensen VL, Janecke AR, Innes AM, Davis EE, Frosk P, Li C, Willer JR, Chodirker BN, Greenberg CR, McLeod DR, Bernier FP, Chudley AE, Müller T, Shboul M, Logan CV, Loucks CM, Beaulieu CL, Bowie RV, Bell SM, Adkins J, Zuniga FI, Ross KD, Wang J, Ban MR, Becker C, Nürnberg P, Douglas S, Craft CM, et al. TMEM237 is mutated in individuals with a Joubert syndrome related disorder and expands the role of the TMEM family at the ciliary transition zone. Am J Hum Genet 2011, 89:713-730.
55. Nikopoulos K, Gilissen C, Hoischen A, van Nouhuys CE, Boonstra FN, Blokland EA, Arts P, Wieskamp N, Strom TM, Ayuso C, Tilanus MA, Bouwhuis S, Mukhopadhyay A, Scheffer H, Hoefsloot LH, Veltman JA, Cremers FP, Collin RW. Next-generation sequencing of a 40 Mb linkage interval reveals TSPAN12 mutations in patients with familial exudative vitreoretinopathy. Am J Hum Genet 2010, 86:240-247.
56. Otto EA, Hurd TW, Airik R, Chaki M, Zhou W, Stoetzel C, Patil SB, Levy S, Ghosh AK, Murga-Zamalloa CA, van Reeuwijk J, Letteboer SJ, Sang L, Giles RH, Liu Q, Coene KL, Estrada-Cuzcano A, Collin RW, McLaughlin HM, Held S, Kasanuki JM, Ramaswami G, Conte J, Lopez I, Washburn J, Macdonald J, Hu J, Yamashita Y, Maher ER, Guay-Woodford LM, et al. Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nat Genet 2010, 42:840-850.
57. Ozgul RK, Siemiatkowska AM, Yucel D, Myers CA, Collin RW, Zonneveld MN, Beryozkin A, Banin E, Hoyng CB, van den Born LI, Bose R, Shen W, Sharon D, Cremers FP, Klevering BJ, den Hollander AI, Corbo JC, European Retinal Disease Consortium Exome sequencing and cis-regulatory mapping identify mutations in MAK, a gene encoding a regulator of ciliary length, as a cause of retinitis pigmentosa. Am J Hum Genet 2011, 89:253-264. European Retinal Disease Consortium.
58. Lee JE, Gleeson JG. A systems-biology approach to understanding the ciliopathy disorders. Genome Med 2011, 3:59.
59. Audo I, Mohand-Said S, Dhaenens CM, Germain A, Orhan E, Antonio A, Hamel C, Sahel JA, Bhattacharya SS, Zeitz C. RP1 and autosomal dominant rod-cone dystrophy: novel mutations, a review of published variants, and genotype-phenotype correlation. Hum Mutat 2012, 33:73-80.
60. Edwards AO. Clinical features of the congenital vitreoretinopathies. Eye (Lond) 2008, 22:1233-1242.
61. Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet 2009, 10:57-63.
62. Morozova O, Hirst M, Marra MA. Applications of new sequencing technologies for transcriptome analysis. Annu Rev Genomics Hum Genet 2009, 10:135-151.
63. Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, Kingsmore SF, Schroth GP, Burge CB. Alternative isoform regulation in human tissue transcriptomes. Nature 2008, 456:470-476.
64. Licatalosi DD, Darnell RB. RNA processing and its regulation: global insights into biological networks. Nat Rev Genet 2010, 11:75-87.
65. Wang GS, Cooper TA. Splicing in disease: disruption of the splicing code and the decoding machinery. Nat Rev Genet 2007, 8:749-761.
66. Kirschner R, Rosenberg T, Schultz-Heienbrok R, Lenzner S, Feil S, Roepman R, Cremers FP, Ropers HH, Berger W. RPGR transcription studies in mouse and human tissues reveal a retina-specific isoform that is disrupted in a patient with X-linked retinitis pigmentosa. Hum Mol Genet 1999, 8:1571-1578.
67. Pretorius PR, Baye LM, Nishimura DY, Searby CC, Bugge K, Yang B, Mullins RF, Stone EM, Sheffield VC, Slusarski DC. Identification and functional analysis of the vision-specific BBS3 (ARL6) long isoform. PLoS Genet 2010, 6:e1000884.
68. Mordes D, Luo X, Kar A, Kuo D, Xu L, Fushimi K, Yu G, Sternberg P, Wu JY. Pre-mRNA splicing and retinitis pigmentosa. Mol Vis 2006, 12:1259-1271.
69. Mercer TR, Gerhardt DJ, Dinger ME, Crawford J, Trapnell C, Jeddeloh JA, Mattick JS, Rinn JL. Targeted RNA sequencing reveals the deep complexity of the human transcriptome. Nat Biotechnol 2012, 30:99-104.
70. Deo M, Yu JY, Chung KH, Tippens M, Turner DL. Detection of mammalian microRNA expression by in situ hybridization with RNA oligonucleotides. Dev Dyn 2006, 235:2538-2548.
71. Xu S, Witmer PD, Lumayag S, Kovacs B, Valle D. MicroRNA (miRNA) transcriptome of mouse retina and identification of a sensory organ-specific miRNA cluster. J Biol Chem 2007, 282:25053-25066.
72. Wang FE, Zhang C, Maminishkis A, Dong L, Zhi C, Li R, Zhao J, Majerciak V, Gaur AB, Chen S, Miller SS. MicroRNA-204/211 alters epithelial physiology. FASEB J 2010, 24:1552-1571.
73. Alfano G, Vitiello C, Caccioppoli C, Caramico T, Carola A, Szego MJ, McInnes RR, Auricchio A, Banfi S. Natural antisense transcripts associated with genes involved in eye development. Hum Mol Genet 2005, 14:913-923.
74. Young TL, Matsuda T, Cepko CL. The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina. Curr Biol 2005, 15:501-512.
75. Rapicavoli NA, Poth EM, Zhu H, Blackshaw S. The long noncoding RNA Six3OS acts in trans to regulate retinal development by modulating Six3 activity. Neural Dev 2011, 6:32.
76. Damiani D, Alexander JJ, O'Rourke JR, McManus M, Jadhav AP, Cepko CL, Hauswirth WW, Harfe BD, Strettoi E. Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina. J Neurosci 2008, 28:4878-4887.
77. Kaneko H, Dridi S, Tarallo V, Gelfand BD, Fowler BJ, Cho WG, Kleinman ME, Ponicsan SL, Hauswirth WW, Chiodo VA, Karikó K, Yoo JW, Lee DK, Hadziahmetovic M, Song Y, Misra S, Chaudhuri G, Buaas FW, Braun RE, Hinton DR, Zhang Q, Grossniklaus HE, Provis JM, Madigan MC, Milam AH, Justice NL, Albuquerque RJ, Blandford AD, Bogdanovich S, Hirano Y, et al. DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration. Nature 2011, 471:325-330.
78. Wittkopp PJ, Kalay G. Cis-regulatory elements: molecular mechanisms and evolutionary processes underlying divergence. Nat Rev Genet 2012, 13:59-69.
79. Corbo JC, Lawrence KA, Karlstetter M, Myers CA, Abdelaziz M, Dirkes W, Weigelt K, Seifert M, Benes V, Fritsche LG, Weber BH, Langmann T. CRX ChIP-seq reveals the cis-regulatory architecture of mouse photoreceptors. Genome Res 2010, 20:1512-1525.
80. Hao H, Kim DS, Klocke B, Johnson KR, Cui K, Gotoh N, Zang C, Gregorski J, Gieser L, Peng W, Fann Y, Seifert M, Zhao K, Swaroop A. Transcriptional regulation of rod photoreceptor homeostasis revealed by in vivo NRL targetome analysis. PLoS Genet 2012, 8:e1002649.
81. Schones DE, Zhao K. Genome-wide approaches to studying chromatin modifications. Nat Rev Genet 2008, 9:179-191.
82. Davis DM, Dyer MA. Retinal progenitor cells, differentiation, and barriers to cell cycle reentry. Curr Top Dev Biol 2010, 93:175-188.
83. Merbs SL, Khan MA, Hackler L, Oliver VF, Wan J, Qian J, Zack DJ. Cell-specific DNA methylation patterns of retina-specific genes. PLoS One 2012, 7:e32602.
84. Hunter A, Spechler PA, Cwanger A, Song Y, Zhang Z, Ying GS, Hunter AK, Dezoeten E, Dunaief JL. DNA methylation is associated with altered gene expression in AMD. Invest Ophthalmol Vis Sci 2012, 53:2089-2105.
85. Bernstein BE, Birney E, Dunham I, Green ED, Gunter C, Snyder M, ENCODE Project Consortium An integrated encyclopedia of DNA elements in the human genome. Nature 2012, 489:57-74. ENCODE Project Consortium.
86. National Human Genome Research Institute Catalog of Published Genome-Wide Association Studies [http://www.genome.gov/gwastudies].
87. Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, Henning AK, SanGiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J. Complement factor H polymorphism in age-related macular degeneration. Science 2005, 308:385-389.
88. Chen W, Stambolian D, Edwards AO, Branham KE, Othman M, Jakobsdottir J, Tosakulwong N, Pericak-Vance MA, Campochiaro PA, Klein ML, Tan PL, Conley YP, Kanda A, Kopplin L, Li Y, Augustaitis KJ, Karoukis AJ, Scott WK, Agarwal A, Kovach JL, Schwartz SG, Postel EA, Brooks M, Baratz KH, Brown WL, Brucker AJ, Orlin A, Brown G, Ho A, , et al. Complications of Age-Related Macular Degeneration Prevention Trial Research Group Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. Proc Natl Acad Sci U S A 2010, 107:7401-7406. Complications of Age-Related Macular Degeneration Prevention Trial Research Group.
89. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll SA, Visscher PM. Finding the missing heritability of complex diseases. Nature 2009, 461:747-753.
90. Gibson G. Rare and common variants: twenty arguments. Nat Rev Genet 2011, 13:135-145.
91. Do R, Kathiresan S, Abecasis GR. Exome sequencing and complex disease: practical aspects of rare variant association studies. Hum Mol Genet 2012, 21:R1-R9.
92. Kiezun A, Garimella K, Do R, Stitziel NO, Neale BM, McLaren PJ, Gupta N, Sklar P, Sullivan PF, Moran JL, Hultman CM, Lichtenstein P, Magnusson P, Lehner T, Shugart YY, Price AL, de Bakker PI, Purcell SM, Sunyaev SR. Exome sequencing and the genetic basis of complex traits. Nat Genet 2012, 44:623-630.
93. DeAngelis MM, Lane AM, Shah CP, Ott J, Dryja TP, Miller JW. Extremely discordant sib-pair study design to determine risk factors for neovascular age-related macular degeneration. Arch Ophthalmol 2004, 122:575-580.
94. Weber BH, Vogt G, Pruett RC, Stohr H, Felbor U. Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby's fundus dystrophy. Nat Genet 1994, 8:352-356.
95. Allikmets R, Singh N, Sun H, Shroyer NF, Hutchinson A, Chidambaram A, Gerrard B, Baird L, Stauffer D, Peiffer A, Rattner A, Smallwood P, Li Y, Anderson KL, Lewis RA, Nathans J, Leppert M, Dean M, Lupski JR. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat Genet 1997, 15:236-246.
96. Allikmets R. Further evidence for an association of ABCR alleles with age-related macular degeneration. The International ABCR Screening Consortium. Am J Hum Genet 2000, 67:487-491.
97. Girirajan S, Campbell CD, Eichler EE. Human copy number variation and complex genetic disease. Annu Rev Genet 2011, 45:203-226.
98. Liu MM, Chan CC, Tuo J. Genetic mechanisms and age-related macular degeneration: common variants, rare variants, copy number variations, epigenetics, and mitochondrial genetics. Hum Genomics 2012, 6:13.
99. Sivakumaran TA, Igo RP, Kidd JM, Itsara A, Kopplin LJ, Chen W, Hagstrom SA, Peachey NS, Francis PJ, Klein ML, Chew EY, Ramprasad VL, Tay WT, Mitchell P, Seielstad M, Stambolian DE, Edwards AO, Lee KE, Leontiev DV, Jun G, Wang Y, Tian L, Qiu F, Henning AK, LaFramboise T, Sen P, Aarthi M, George R, Raman R, Das MK, et al. A 32 kb critical region excluding Y402H in CFH mediates risk for age-related macular degeneration. PLoS One 2011, 6:e25598.
100. Meyer KJ, Davis LK, Schindler EI, Beck JS, Rudd DS, Grundstad AJ, Scheetz TE, Braun TA, Fingert JH, Alward WL, Kwon YH, Folk JC, Russell SR, Wassink TH, Stone EM, Sheffield VC. Genome-wide analysis of copy number variants in age-related macular degeneration. Hum Genet 2011, 129:91-100.
101. Hageman GS, Hancox LS, Taiber AJ, Gehrs KM, Anderson DH, Johnson LV, Radeke MJ, Kavanagh D, Richards A, Atkinson J, Meri S, Bergeron J, Zernant J, Merriam J, Gold B, Allikmets R, Dean M, AMD Clinical Study Group Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: characterization, ethnic distribution and evolutionary implications. Ann Med 2006, 38:592-604. AMD Clinical Study Group.
102. Hughes AE, Orr N, Esfandiary H, Diaz-Torres M, Goodship T, Chakravarthy U. A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration. Nat Genet 2006, 38:1173-1177.
103. Spencer KL, Hauser MA, Olson LM, Schmidt S, Scott WK, Gallins P, Agarwal A, Postel EA, Pericak-Vance MA, Haines JL. Deletion of CFHR3 and CFHR1 genes in age-related macular degeneration. Hum Mol Genet 2008, 17:971-977.
104. Liu MM, Agron E, Chew E, Meyerle C, Ferris FL, Chan CC, Tuo J. Copy number variations in candidate genes in neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci 2011, 52:3129-3135.
105. Korbel JO, Urban AE, Affourtit JP, Godwin B, Grubert F, Simons JF, Kim PM, Palejev D, Carriero NJ, Du L, Taillon BE, Chen Z, Tanzer A, Saunders AC, Chi J, Yang F, Carter NP, Hurles ME, Weissman SM, Harkins TT, Gerstein MB, Egholm M, Snyder M. Paired-end mapping reveals extensive structural variation in the human genome. Science 2007, 318:420-426.
106. Tuzun E, Sharp AJ, Bailey JA, Kaul R, Morrison VA, Pertz LM, Haugen E, Hayden H, Albertson D, Pinkel D, Olson MV, Eichler EE. Fine-scale structural variation of the human genome. Nat Genet 2005, 37:727-732.
107. Alkan C, Coe BP, Eichler EE. Genome structural variation discovery and genotyping. Nat Rev Genet 2011, 12:363-376.
108. Bodmer W, Bonilla C. Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet 2008, 40:695-701.
109. Pritchard JK. Are rare variants responsible for susceptibility to complex diseases?. Am J Hum Genet 2001, 69:124-137.
110. Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, Kang HM, Marth GT, McVean GA, 1000 Genomes Project Consortium An integrated map of genetic variation from 1,092 human genomes. Nature 2012, 491:56-65. 1000 Genomes Project Consortium.
111. Fu W, O'Connor TD, Jun G, Kang HM, Abecasis G, Leal SM, Gabriel S, Rieder MJ, Altshuler D, Shendure J, Nickerson DA, Bamshad MJ, Akey JM, NHLBI Exome Sequencing Project Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants. Nature 2013, 493:216-220. NHLBI Exome Sequencing Project.
112. Exome Chip Design [http://genome.sph.umich.edu/wiki/Exome_Chip_Design].
113. Cheung VG, Spielman RS, Ewens KG, Weber TM, Morley M, Burdick JT. Mapping determinants of human gene expression by regional and genome-wide association. Nature 2005, 437:1365-1369.
114. Majewski J, Pastinen T. The study of eQTL variations by RNA-seq: from SNPs to phenotypes. Trends Genet 2011, 27:72-79.
115. Cooper GM, Shendure J. Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data. Nat Rev Genet 2011, 12:628-640.
116. Branham K, Othman M, Brumm M, Karoukis AJ, Atmaca-Sonmez P, Yashar BM, Schwartz SB, Stover NB, Trzupek K, Wheaton D, Jennings B, Ciccarelli ML, Jayasundera KT, Lewis RA, Birch D, Bennett J, Sieving PA, Andreasson S, Duncan JL, Fishman GA, Iannaccone A, Weleber RG, Jacobson SG, Heckenlively JR, Swaroop A. Mutations in RPGR and RP2 account for 15% of males with simplex retinal degenerative disease. Invest Ophthalmol Vis Sci 2012, 53:8232-8237.
117. Churchill JD, Bowne SJ, Sullivan LS, Lewis RA, Wheaton DK, Birch DG, Branham KE, Heckenlively JR, Daiger SP. Mutations in the X-linked retinitis pigmentosa genes RPGR and RP2 found in 8.5% of families with a provisional diagnosis of autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci 2013, 54:1411-1416.
118. Swaroop A. What's in a name? RPGR mutations redefine the genetic and phenotypic landscape in retinal degenerative diseases. Invest Ophthalmol Vis Sci 2013, 54:1417.
119. Bowne SJ, Sullivan LS, Koboldt DC, Ding L, Fulton R, Abbott RM, Sodergren EJ, Birch DG, Wheaton DH, Heckenlively JR, Liu Q, Pierce EA, Weinstock GM, Daiger SP. Identification of disease-causing mutations in autosomal dominant retinitis pigmentosa (adRP) using next-generation DNA sequencing. Invest Ophthalmol Vis Sci 2011, 52:494-503.
120. Neveling K, Collin RW, Gilissen C, van Huet RA, Visser L, Kwint MP, Gijsen SJ, Zonneveld MN, Wieskamp N, de Ligt J, Siemiatkowska AM, Hoefsloot LH, Buckley MF, Kellner U, Branham KE, den Hollander AI, Hoischen A, Hoyng C, Klevering BJ, van den Born LI, Veltman JA, Cremers FP, Scheffer H. Next-generation genetic testing for retinitis pigmentosa. Hum Mutat 2012, 33:963-972.
121. Booij JC, Bakker A, Kulumbetova J, Moutaoukil Y, Smeets B, Verheij J, Kroes HY, Klaver CC, van Schooneveld M, Bergen AA, Florijn RJ. Simultaneous mutation detection in 90 retinal disease genes in multiple patients using a custom-designed 300-kb retinal resequencing chip. Ophthalmology 2011, 118:160-167. e1-3.
122. Song J, Smaoui N, Ayyagari R, Stiles D, Benhamed S, MacDonald IM, Daiger SP, Tumminia SJ, Hejtmancik F, Wang X. High-throughput retina-array for screening 93 genes involved in inherited retinal dystrophy. Invest Ophthalmol Vis Sci 2011, 52:9053-9060.
123. Blain D, Goetz KE, Ayyagari R, Tumminia SJ. eyeGENE(R): a vision community resource facilitating patient care and paving the path for research through molecular diagnostic testing. Clin Genet 2013, 84:190-197.
124. Haider NB, Ikeda A, Naggert JK, Nishina PM. Genetic modifiers of vision and hearing. Hum Mol Genet 2002, 11:1195-1206.
125. Nadeau JH. Modifier genes in mice and humans. Nat Rev Genet 2001, 2:165-174.
126. Kajiwara K, Berson EL, Dryja TP. Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci. Science 1994, 264:1604-1608.
127. Poloschek CM, Bach M, Lagreze WA, Glaus E, Lemke JR, Berger W, Neidhardt J. ABCA4 and ROM1: implications for modification of the PRPH2-associated macular dystrophy phenotype. Invest Ophthalmol Vis Sci 2010, 51:4253-4265.
128. Venturini G, Rose AM, Shah AZ, Bhattacharya SS, Rivolta C. CNOT3 is a modifier of PRPF31 mutations in retinitis pigmentosa with incomplete penetrance. PLoS Genet 2012, 8:e1003040.
129. Wiszniewski W, Lewis RA, Stockton DW, Peng J, Mardon G, Chen R, Lupski JR. Potential involvement of more than one locus in trait manifestation for individuals with Leber congenital amaurosis. Hum Genet 2011, 129:319-327.
130. Hildebrandt F, Benzing T, Katsanis N. Ciliopathies. N Engl J Med 2011, 364:1533-1543.
131. Rachel RA, Li T, Swaroop A. Photoreceptor sensory cilia and ciliopathies: focus on CEP290, RPGR and their interacting proteins. Cilia 2012, 1:22.
132. Khanna H, Davis EE, Murga-Zamalloa CA, Estrada-Cuzcano A, Lopez I, den Hollander AI, Zonneveld MN, Othman MI, Waseem N, Chakarova CF, Maubaret C, Diaz-Font A, MacDonald I, Muzny DM, Wheeler DA, Morgan M, Lewis LR, Logan CV, Tan PL, Beer MA, Inglehearn CF, Lewis RA, Jacobson SG, Bergmann C, Beales PL, Attié-Bitach T, Johnson CA, Otto EA, Bhattacharya SS, Hildebrandt F, et al. A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies. Nat Genet 2009, 41:739-745.
133. Coppieters F, Casteels I, Meire F, De Jaegere S, Hooghe S, van Regemorter N, Van Esch H, Matuleviciene A, Nunes L, Meersschaut V, Walraedt S, Standaert L, Coucke P, Hoeben H, Kroes HY, Vande Walle J, de Ravel T, Leroy BP, De Baere E. Genetic screening of LCA in Belgium: predominance of CEP290 and identification of potential modifier alleles in AHI1 of CEP290-related phenotypes. Hum Mutat 2010, 31:E1709-E1766.
134. Louie CM, Caridi G, Lopes VS, Brancati F, Kispert A, Lancaster MA, Schlossman AM, Otto EA, Leitges M, Gröne HJ, Lopez I, Gudiseva HV, O'Toole JF, Vallespin E, Ayyagari R, Ayuso C, Cremers FP, den Hollander AI, Koenekoop RK, Dallapiccola B, Ghiggeri GM, Hildebrandt F, Valente EM, Williams DS, Gleeson JG. AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisis. Nat Genet 2010, 42:175-180.
135. Ebermann I, Phillips JB, Liebau MC, Koenekoop RK, Schermer B, Lopez I, Schafer E, Roux AF, Dafinger C, Bernd A, Zrenner E, Claustres M, Blanco B, Nürnberg G, Nürnberg P, Ruland R, Westerfield M, Benzing T, Bolz HJ. PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome. J Clin Invest 2010, 120:1812-1823.
136. Rachel RA, May-Simera HL, Veleri S, Gotoh N, Choi BY, Murga-Zamalloa C, McIntyre JC, Marek J, Lopez I, Hackett AN, Zhang J, Brooks M, den Hollander AI, Beales PL, Li T, Jacobson SG, Sood R, Martens JR, Liu P, Friedman TB, Khanna H, Koenekoop RK, Kelley MW, Swaroop A. Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis. J Clin Invest 2012, 122:1233-1245.