Saturation of the human phenome

Current Genomics

Volumn 11, Issue 7, 2010, Pages 482-499

  Samuels, Mark E ^a  

^a UNIVERSITY OF MONTREAL   (Canada)

Author keywords

Genetics; Human genome; Phenome; Saturation mutagenesis

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE;

ALLELE; ARTICLE; AUTOSOMAL DOMINANT INHERITANCE; AUTOSOMAL RECESSIVE INHERITANCE; GENE; GENE LOCUS; GENE MUTATION; GENETIC TRAIT; GENETIC VARIABILITY; HUMAN; HUMAN GENOME; MUTAGENESIS; PHENOTYPE; RECESSIVE INHERITANCE; SEQUENCE ANALYSIS; TRANSPOSON;

ANIMALIA; CAENORHABDITIS ELEGANS; DANIO RERIO; DROSOPHILA MELANOGASTER; MUS MUSCULUS; SACCHAROMYCES CEREVISIAE;

EID: 78650003038     PISSN: 13892029     EISSN: None     Source Type: Journal    
DOI: 10.2174/138920210793175886     Document Type: Article

References (247)

1. Freimer, N.; Sabatti, C. The human phenome project. Nat. Genet., 2003, 34, 15-21.
2. Oti, M.; Huynen, M.A.; Brunner, H.G. Phenome connections. Trends Genet., 2008, 24, 103-106.
3. Oti, M.; Huynen, M.A.; Brunner, H.G. The biological coherence of human phenome databases. Am. J. Hum. Genet., 2009, 85, 801-808.
4. Scriver, C.R. After the genome-the phenome? J. Inherit. Metab. Dis., 2004, 27, 305-317.
5. Paulson, H.L. The spinocerebellar ataxias. J. Neuroophthalmol., 2009, 29, 227-237.
6. Dror, A.A.; Avraham, K.B. Hearing loss: mechanisms revealed by genetics and cell biology. Annu. Rev. Genet., 2009, 43, 411-437.
7. Matsunaga, T. Value of genetic testing in the otological approach for sensorineural hearing loss. Keio J. Med., 2009, 58, 216-222.
8. Hilgert, N.; Smith, R.J.; Van Camp, G. Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics? Mutat. Res., 2009, 681, 189-196.
9. Berger, W.; Kloeckener-Gruissem, B.; Neidhardt, J. The molecular basis of human retinal and vitreoretinal diseases. Prog. Retin. Eye Res., 2010, 29(5), 335-375.
10. Phelan, J.K.; Bok, D. A brief review of retinitis pigmentosa and the identified retinitis pigmentosa genes. Mol. Vis., 2000, 6, 116-124.
11. van Soest, S.; Westerveld, A.; de Jong, P.T.; Bleeker-Wagemakers, E.M.; Bergen, A.A. Retinitis pigmentosa: defined from a molecular point of view. Surv. Ophthalmol., 1999, 43, 321-334.
12. Banchs, I.; Casasnovas, C.; Alberti, A.; De Jorge, L.; Povedano, M.; Montero, J.; Martinez-Matos, J.A.; Volpini, V. Diagnosis of Charcot-Marie-Tooth disease. J. Biomed. Biotechnol., 2009, 2009, 985415.
13. Barisic, N.; Claeys, K.G.; Sirotkovic-Skerlev, M.; Lofgren, A.; Nelis, E.; De Jonghe, P.; Timmerman, V. Charcot-Marie-Tooth disease: a clinico-genetic confrontation. Ann. Hum. Genet., 2008, 72, 416-441.
14. Casasnovas, C.; Cano, L.M.; Alberti, A.; Cespedes, M.; Rigo, G. Charcot-Marie-tooth disease. Foot Ankle Spec., 2008, 1, 350-354.
15. Jani-Acsadi, A.; Krajewski, K.; Shy, M.E. Charcot-Marie-Tooth neuropathies: diagnosis and management. Semin. Neurol., 2008, 28, 185-194.
16. Pareyson, D.; Marchesi, C.; Salsano, E. Hereditary predominantly motor neuropathies. Curr. Opin. Neurol., 2009, 22, 451-459.
17. Parman, Y. Hereditary neuropathies. Curr. Opin. Neurol., 2007, 20, 542-547.
18. Reilly, M.M. Sorting out the inherited neuropathies. Pract. Neurol., 2007, 7, 93-105.
19. Szigeti, K.; Nelis, E.; Lupski, J.R. Molecular diagnostics of Charcot-Marie-Tooth disease and related peripheral neuropathies. Neuromolecular Med., 2006, 8, 243-254.
20. Dragatsis, I.; Efstratiadis, A.; Zeitlin, S. Mouse mutant embryos lacking huntingtin are rescued from lethality by wild-type extraembryonic tissues. Development, 1998, 125, 1529-1539.
21. Kajiwara, K.; Berson, E.L.; Dryja, T.P. Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci. Science, 1994, 264, 1604-1608.
22. Dryja, T.P.; Hahn, L.B.; Kajiwara, K.; Berson, E.L. Dominant and digenic mutations in the peripherin/RDS and ROM1 genes in retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci., 1997, 38, 1972-1982.
23. Goldberg, A.F.; Molday, R.S. Defective subunit assembly underlies a digenic form of retinitis pigmentosa linked to mutations in peripherin/rds and rom-1. Proc. Natl. Acad. Sci. USA, 1996, 93, 13726-13730.
24. Jin, Z.B.; Mandai, M.; Yokota, T.; Higuchi, K.; Ohmori, K.; Ohtsuki, F.; Takakura, S.; Itabashi, T.; Wada, Y.; Akimoto, M.; Ooto, S.; Suzuki, T.; Hirami, Y.; Ikeda, H.; Kawagoe, N.; Oishi, A.; Ichiyama, S.; Takahashi, M.; Yoshimura, N.; Kosugi, S. Identifying pathogenic genetic background of simplex or multiplex retinitis pigmentosa patients: a large scale mutation screening study. J. Med. Genet., 2008, 45, 465-472.
25. Kedzierski, W.; Nusinowitz, S.; Birch, D.; Clarke, G.; McInnes, R.R.; Bok, D.; Travis, G.H. Deficiency of rds/peripherin causes photoreceptor death in mouse models of digenic and dominant retinitis pigmentosa. Proc. Natl. Acad. Sci. USA, 2001, 98, 7718-7723.
26. Keen, T.J.; Inglehearn, C.F. Mutations and polymorphisms in the human peripherin-RDS gene and their involvement in inherited retinal degeneration. Hum. Mutat., 1996, 8, 297-303.
27. Loewen, C.J.; Moritz, O.L.; Molday, R.S. Molecular characterization of peripherin-2 and rom-1 mutants responsible for digenic retinitis pigmentosa. J. Biol. Chem., 2001, 276, 22388-22396.
28. Sullivan, L.S.; Bowne, S.J.; Birch, D.G.; Hughbanks-Wheaton, D.; Heckenlively, J.R.; Lewis, R.A.; Garcia, C.A.; Ruiz, R.S.; Blanton, S.H.; Northrup, H.; Gire, A.I.; Seaman, R.; Duzkale, H.; Spellicy, C.J.; Zhu, J.; Shankar, S.P.; Daiger, S.P. Prevalence of diseasecausing mutations in families with autosomal dominant retinitis pigmentosa: a screen of known genes in 200 families. Invest. Ophthalmol. Vis. Sci., 2006, 47, 3052-3064.
29. Jacolot, S.; Le Gac, G.; Scotet, V.; Quere, I.; Mura, C.; Ferec, C. HAMP as a modifier gene that increases the phenotypic expression of the HFE pC282Y homozygous genotype. Blood, 2004, 103, 2835-2840.
30. Merryweather-Clarke, A.T.; Cadet, E.; Bomford, A.; Capron, D.; Viprakasit, V.; Miller, A.; McHugh, P.J.; Chapman, R.W.; Pointon, J.J.; Wimhurst, V.L.; Livesey, K.J.; Tanphaichitr, V.; Rochette, J.; Robson, K.J. Digenic inheritance of mutations in HAMP and HFE results in different types of haemochromatosis. Hum. Mol. Genet., 2003, 12, 2241-2247.
31. Badano, J.L.; Kim, J.C.; Hoskins, B.E.; Lewis, R.A.; Ansley, S.J.; Cutler, D.J.; Castellan, C.; Beales, P.L.; Leroux, M.R.; Katsanis, N. Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic effect on Bardet-Biedl patients with two mutations at a second BBS locus. Hum. Mol. Genet., 2003, 12, 1651-1659.
32. Badano, J.L.; Leitch, C.C.; Ansley, S.J.; May-Simera, H.; Lawson, S.; Lewis, R.A.; Beales, P.L.; Dietz, H.C.; Fisher, S.; Katsanis, N. Dissection of epistasis in oligogenic Bardet-Biedl syndrome. Nature, 2006, 439, 326-330.
33. Beales, P.L.; Badano, J.L.; Ross, A.J.; Ansley, S.J.; Hoskins, B.E.; Kirsten, B.; Mein, C.A.; Froguel, P.; Scambler, P.J.; Lewis, R.A.; Lupski, J.R.; Katsanis, N. Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non-Mendelian Bardet-Biedl syndrome. Am. J. Hum. Genet., 2003, 72, 1187-1199.
34. Eichers, E.R.; Lewis, R.A.; Katsanis, N.; Lupski, J.R. Triallelic inheritance: a bridge between Mendelian and multifactorial traits. Ann. Med., 2004, 36, 262-272.
35. Fauser, S.; Munz, M.; Besch, D. Further support for digenic inheritance in Bardet-Biedl syndrome. J. Med. Genet., 2003, 40, e104.
36. Katsanis, N. The oligogenic properties of Bardet-Biedl syndrome. Hum. Mol. Genet., 2004, 13 Spec No 1, R65-71.
37. Adato, A.; Kalinski, H.; Weil, D.; Chaib, H.; Korostishevsky, M.; Bonne-Tamir, B. Possible interaction between USH1B and USH3 gene products as implied by apparent digenic deafness inheritance. Am. J. Hum. Genet., 1999, 65, 261-265.
38. Cama, E.; Melchionda, S.; Palladino, T.; Carella, M.; Santarelli, R.; Genovese, E.; Benettazzo, F.; Zelante, L.; Arslan, E. Hearing loss features in GJB2 biallelic mutations and GJB2/GJB6 digenic inheritance in a large Italian cohort. Int. J. Audiol., 2009, 48, 12-17.
39. Chen, A.H.; Fukushima, K.; McGuirt, W.T.; Smith, R.J. DFNB15: autosomal recessive non-syndromic hearing loss gene-chromosome 3q, 19p or digenic recessive inheritance? Adv. Otorhinolaryngol., 2000, 56, 171-175.
40. Liu, X.Z.; Yuan, Y.; Yan, D.; Ding, E.H.; Ouyang, X.M.; Fei, Y.; Tang, W.; Yuan, H.; Chang, Q.; Du, L.L.; Zhang, X.; Wang, G.; Ahmad, S.; Kang, D.Y.; Lin, X.; Dai, P. Digenic inheritance of non-syndromic deafness caused by mutations at the gap junction proteins Cx26 and Cx31. Hum. Genet., 2009, 125, 53-62.
41. Morell, R.; Spritz, R.A.; Ho, L.; Pierpont, J.; Guo, W.; Friedman, T.B.; Asher, J.H., Jr. Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA). Hum. Mol. Genet., 1997, 6, 659-664.
42. Nozu, K.; Inagaki, T.; Fu, X.J.; Nozu, Y.; Kaito, H.; Kanda, K.; Sekine, T.; Igarashi, T.; Nakanishi, K.; Yoshikawa, N.; Iijima, K.; Matsuo, M. Molecular analysis of digenic inheritance in Bartter syndrome with sensorineural deafness. J. Med. Genet., 2008, 45, 182-186.
43. Pallares-Ruiz, N.; Blanchet, P.; Mondain, M.; Claustres, M.; Roux, A.F. A large deletion including most of GJB6 in recessive non syndromic deafness: a digenic effect? Eur. J. Hum. Genet., 2002, 10, 72-76.
44. Stevenson, V.A.; Ito, M.; Milunsky, J.M. Connexin-30 deletion analysis in connexin-26 heterozygotes. Genet. Test., 2003, 7, 151-154.
45. Yang, T.; Gurrola, J.G., 2nd; Wu, H.; Chiu, S.M.; Wangemann, P.; Snyder, P.M.; Smith, R.J. Mutations of KCNJ10 together with mutations of SLC26A4 cause digenic nonsyndromic hearing loss associated with enlarged vestibular aqueduct syndrome. Am. J. Hum. Genet., 2009, 84, 651-657.
46. Zheng, Q.Y.; Yan, D.; Ouyang, X.M.; Du, L.L.; Yu, H.; Chang, B.; Johnson, K.R.; Liu, X.Z. Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans. Hum. Mol. Genet., 2005, 14, 103-111.
47. Weatherall, D.J. Single gene disorders or complex traits: lessons from the thalassaemias and other monogenic diseases. BMJ, 2000, 321, 1117-1120.
48. Weatherall, D.J. Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias. Nat. Rev. Genet., 2001, 2, 245-255.
49. Scriver, C.R.; Waters, P.J. Monogenic traits are not simple: lessons from phenylketonuria. Trends Genet., 1999, 15, 267-272.
50. Charlton, R.; Bothwell, T. Current clinical practice: hereditary haemochromatosis: recent advances in biology and management. Hematology, 1999, 4, 185-194.
51. Weatherall, M.W.; Higgs, D.R.; Weiss, H.; Weatherall, D.J.; Serjeant, G.R. Phenotype/genotype relationships in sickle cell disease: a pilot twin study. Clin. Lab. Haematol., 2005, 27, 384-390.
52. Dipple, K.M.; McCabe, E.R. Modifier genes convert simple Mendelian disorders to complex traits. Mol. Genet. Metab., 2000, 71, 43-50.
53. Dipple, K.M.; McCabe, E.R. Phenotypes of patients with simple Mendelian disorders are complex traits: thresholds, modifiers, and systems dynamics. Am. J. Hum. Genet., 2000, 66, 1729-1735.
54. Boyle, M.P. Strategies for identifying modifier genes in cystic fibrosis. Proc. Am. Thorac. Soc., 2007, 4, 52-57.
55. Collaco, J.M.; Cutting, G.R. Update on gene modifiers in cystic fibrosis. Curr. Opin. Pulm. Med., 2008, 14, 559-566.
56. Merlo, C.A.; Boyle, M.P. Modifier genes in cystic fibrosis lung disease. J. Lab. Clin. Med., 2003, 141, 237-241.
57. Slieker, M.G.; Sanders, E.A.; Rijkers, G.T.; Ruven, H.J.; van der Ent, C.K. Disease modifying genes in cystic fibrosis. J. Cyst. Fibros., 2005, 4(Suppl 2), 7-13.
58. Roy, C.N.; Andrews, N.C. Recent advances in disorders of iron metabolism: mutations, mechanisms and modifiers. Hum. Mol. Genet., 2001, 10, 2181-2186.
59. Wood, M.J.; Powell, L.W.; Ramm, G.A. Environmental and genetic modifiers of the progression to fibrosis and cirrhosis in hemochromatosis. Blood, 2008, 111, 4456-4462.
60. Edwards, A.O.; Ritter, R., 3rd; Abel, K.J.; Manning, A.; Panhuysen, C.; Farrer, L.A. Complement factor H polymorphism and age-related macular degeneration. Science, 2005, 308, 421-424.
61. Hageman, G.S.; Anderson, D.H.; Johnson, L.V.; Hancox, L.S.; Taiber, A.J.; Hardisty, L.I.; Hageman, J.L.; Stockman, H.A.; Borchardt, J.D.; Gehrs, K.M.; Smith, R.J.; Silvestri, G.; Russell, S.R.; Klaver, C.C.; Barbazetto, I.; Chang, S.; Yannuzzi, L.A.; Barile, G.R.; Merriam, J.C.; Smith, R.T.; Olsh, A.K.; Bergeron, J.; Zernant, J.; Merriam, J.E.; Gold, B.; Dean, M.; Allikmets, R. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc. Natl. Acad. Sci. USA, 2005, 102, 7227-7232.
62. Haines, J.L.; Hauser, M.A.; Schmidt, S.; Scott, W.K.; Olson, L.M.; Gallins, P.; Spencer, K.L.; Kwan, S.Y.; Noureddine, M.; Gilbert, J.R.; Schnetz-Boutaud, N.; Agarwal, A.; Postel, E.A.; Pericak-Vance, M.A. Complement factor H variant increases the risk of age-related macular degeneration. Science, 2005, 308, 419-421.
63. Klein, R.J.; Zeiss, C.; Chew, E.Y.; Tsai, J.Y.; Sackler, R.S.; Haynes, C.; Henning, A.K.; SanGiovanni, J.P.; Mane, S.M.; Mayne, S.T.; Bracken, M.B.; Ferris, F.L.; Ott, J.; Barnstable, C.; Hoh, J. Complement factor H polymorphism in age-related macular degeneration. Science, 2005, 308, 385-389.
64. Drayna, D.; Coon, H.; Kim, U.K.; Elsner, T.; Cromer, K.; Otterud, B.; Baird, L.; Peiffer, A.P.; Leppert, M. Genetic analysis of a complex trait in the Utah Genetic Reference Project: a major locus for PTC taste ability on chromosome 7q and a secondary locus on chromosome 16p. Hum. Genet., 2003, 112, 567-572.
65. Wooding, S.; Kim, U.K.; Bamshad, M.J.; Larsen, J.; Jorde, L.B.; Drayna, D. Natural selection and molecular evolution in PTC, a bitter-taste receptor gene. Am. J. Hum. Genet., 2004, 74, 637-646.
66. Eriksson, N.; Macpherson, J.M.; Tung, J.Y.; Hon, L.S.; Naughton, B.; Saxonov, S.; Avey, L.; Wojcicki, A.; Pe'er, I.; Mountain, J. Web-based, participant-driven studies yield novel genetic associations for common traits. PLoS Genet., 2010, 6, e1000993.
67. Weedon, M.N.; Frayling, T.M. Reaching new heights: insights into the genetics of human stature. Trends Genet., 2008, 24, 595-603.
68. Sturm, R.A. Molecular genetics of human pigmentation diversity. Hum. Mol. Genet., 2009, 18, R9-17.
69. Sturm, R.A.; Duffy, D.L.; Box, N.F.; Newton, R.A.; Shepherd, A.G.; Chen, W.; Marks, L.H.; Leonard, J.H.; Martin, N.G. Genetic association and cellular function of MC1R variant alleles in human pigmentation. Ann. N. Y. Acad. Sci., 2003, 994, 348-358.
70. Sturm, R.A.; Larsson, M. Genetics of human iris colour and patterns. Pigment Cell Melanoma Res., 2009, 22, 544-562.
71. Antequera, F.; Bird, A. Number of CpG islands and genes in human and mouse. Proc. Natl. Acad. Sci. USA, 1993, 90, 11995-11999.
72. Roest Crollius, H.; Jaillon, O.; Bernot, A.; Dasilva, C.; Bouneau, L.; Fischer, C.; Fizames, C.; Wincker, P.; Brottier, P.; Quetier, F.; Saurin, W.; Weissenbach, J. Estimate of human gene number provided by genome-wide analysis using Tetraodon nigroviridis DNA sequence. Nat. Genet., 2000, 25, 235-238.
73. Imanishi, T.; Itoh, T.; Suzuki, Y.; O'Donovan, C.; Fukuchi, S.; Koyanagi, K.O.; Barrero, R.A.; Tamura, T.; Yamaguchi-Kabata, Y.; Tanino, M.; Yura, K.; Miyazaki, S.; Ikeo, K.; Homma, K.; Kasprzyk, A.; Nishikawa, T.; Hirakawa, M.; Thierry-Mieg, J.; Thierry-Mieg, D.; Ashurst, J.; Jia, L.; Nakao, M.; Thomas, M.A.; Mulder, N.; Karavidopoulou, Y.; Jin, L.; Kim, S.; Yasuda, T.; Lenhard, B.; Eveno, E.; Suzuki, Y.; Yamasaki, C.; Takeda, J.; Gough, C.; Hilton, P.; Fujii, Y.; Sakai, H.; Tanaka, S.; Amid, C.; Bellgard, M.; Bonaldo Mde, F.; Bono, H.; Bromberg, S.K.; Brookes, A.J.; Bruford, E.; Carninci, P.; Chelala, C.; Couillault, C.; de Souza, S.J.; Debily, M.A.; Devignes, M.D.; Dubchak, I.; Endo, T.; Estreicher, A.; Eyras, E.; Fukami-Kobayashi, K.; Gopinath, G.R.; Graudens, E.; Hahn, Y.; Han, M.; Han, Z.G.; Hanada, K.; Hanaoka, H.; Harada, E.; Hashimoto, K.; Hinz, U.; Hirai, M.; Hishiki, T.; Hopkinson, I.; Imbeaud, S.; Inoko, H.; Kanapin, A.; Kaneko, Y.; Kasukawa, T.; Kelso, J.; Kersey, P.; Kikuno, R.; Kimura, K.; Korn, B.; Kuryshev, V.; Makalowska, I.; Makino, T.; Mano, S.; Mariage-Samson, R.; Mashima, J.; Matsuda, H.; Mewes, H.W.; Minoshima, S.; Nagai, K.; Nagasaki, H.; Nagata, N.; Nigam, R.; Ogasawara, O.; Ohara, O.; Ohtsubo, M.; Okada, N.; Okido, T.; Oota, S.; Ota, M.; Ota, T.; Otsuki, T.; Piatier-Tonneau, D.; Poustka, A.; Ren, S.X.; Saitou, N.; Sakai, K.; Sakamoto, S.; Sakate, R.; Schupp, I.; Servant, F.; Sherry, S.; Shiba, R.; Shimizu, N.; Shimoyama, M.; Simpson, A.J.; Soares, B.; Steward, C.; Suwa, M.; Suzuki, M.; Takahashi, A.; Tamiya, G.; Tanaka, H.; Taylor, T.; Terwilliger, J.D.; Unneberg, P.; Veeramachaneni, V.; Watanabe, S.; Wilming, L.; Yasuda, N.; Yoo, H.S.; Stodolsky, M.; Makalowski, W.; Go, M.; Nakai, K.; Takagi, T.; Kanehisa, M.; Sakaki, Y.; Quackenbush, J.; Okazaki, Y.; Hayashizaki, Y.; Hide, W.; Chakraborty, R.; Nishikawa, K.; Sugawara, H.; Tateno, Y.; Chen, Z.; Oishi, M.; Tonellato, P.; Apweiler, R.; Okubo, K.; Wagner, L.; Wiemann, S.; Strausberg, R.L.; Isogai, T.; Auffray, C.; Nomura, N.; Gojobori, T.; Sugano, S. Integrative annotation of 21,037 human genes validated by full-length cDNA clones. PLoS Biol., 2004, 2, e162.
74. Yamasaki, C.; Koyanagi, K.O.; Fujii, Y.; Itoh, T.; Barrero, R.; Tamura, T.; Yamaguchi-Kabata, Y.; Tanino, M.; Takeda, J.; Fukuchi, S.; Miyazaki, S.; Nomura, N.; Sugano, S.; Imanishi, T.; Gojobori, T. Investigation of protein functions through data-mining on integrated human transcriptome database, H-Invitational database (H-InvDB). Gene, 2005, 364, 99-107.
75. Clamp, M.; Fry, B.; Kamal, M.; Xie, X.; Cuff, J.; Lin, M.F.; Kellis, M.; Lindblad-Toh, K.; Lander, E.S. Distinguishing protein-coding and noncoding genes in the human genome. Proc. Natl. Acad. Sci. USA, 2007, 104, 19428-19433.
76. Ashurst, J.L.; Chen, C.K.; Gilbert, J.G.; Jekosch, K.; Keenan, S.; Meidl, P.; Searle, S.M.; Stalker, J.; Storey, R.; Trevanion, S.; Wilming, L.; Hubbard, T. The Vertebrate Genome Annotation (Vega) database. Nucleic Acids Res., 2005, 33, D459-65.
77. Wilming, L.G.; Gilbert, J.G.; Howe, K.; Trevanion, S.; Hubbard, T.; Harrow, J.L. The vertebrate genome annotation (Vega) database. Nucleic Acids Res., 2008, 36, D753-60.
78. Pruitt, K.D.; Harrow, J.; Harte, R.A.; Wallin, C.; Diekhans, M.; Maglott, D.R.; Searle, S.; Farrell, C.M.; Loveland, J.E.; Ruef, B.J.; Hart, E.; Suner, M.M.; Landrum, M.J.; Aken, B.; Ayling, S.; Baertsch, R.; Fernandez-Banet, J.; Cherry, J.L.; Curwen, V.; Dicuccio, M.; Kellis, M.; Lee, J.; Lin, M.F.; Schuster, M.; Shkeda, A.; Amid, C.; Brown, G.; Dukhanina, O.; Frankish, A.; Hart, J.; Maidak, B.L.; Mudge, J.; Murphy, M.R.; Murphy, T.; Rajan, J.; Rajput, B.; Riddick, L.D.; Snow, C.; Steward, C.; Webb, D.; Weber, J.A.; Wilming, L.; Wu, W.; Birney, E.; Haussler, D.; Hubbard, T.; Ostell, J.; Durbin, R.; Lipman, D. The consensus coding sequence (CCDS) project: Identifying a common protein-coding gene set for the human and mouse genomes. Genome Res., 2009, 19, 1316-1323.
79. Pan, Q.; Shai, O.; Lee, L.J.; Frey, B.J.; Blencowe, B.J. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat. Genet., 2008, 40, 1413-1415.
80. Sultan, M.; Schulz, M.H.; Richard, H.; Magen, A.; Klingenhoff, A.; Scherf, M.; Seifert, M.; Borodina, T.; Soldatov, A.; Parkhomchuk, D.; Schmidt, D.; O'Keeffe, S.; Haas, S.; Vingron, M.; Lehrach, H.; Yaspo, M.L. A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science, 2008, 321, 956-960.
81. Anderson, S.; Bankier, A.T.; Barrell, B.G.; de Bruijn, M.H.; Coulson, A.R.; Drouin, J.; Eperon, I.C.; Nierlich, D.P.; Roe, B.A.; Sanger, F.; Schreier, P.H.; Smith, A.J.; Staden, R.; Young, I.G. Sequence and organization of the human mitochondrial genome. Nature, 1981, 290, 457-465.
82. Elstner, M.; Andreoli, C.; Ahting, U.; Tetko, I.; Klopstock, T.; Meitinger, T.; Prokisch, H. MitoP2: an integrative tool for the analysis of the mitochondrial proteome. Mol. Biotechnol., 2008, 40, 306-315.
83. Elstner, M.; Andreoli, C.; Klopstock, T.; Meitinger, T.; Prokisch, H. The mitochondrial proteome database: MitoP2. Methods Enzymol., 2009, 457, 3-20.
84. Miklos, G.L.; Rubin, G.M. The role of the genome project in determining gene function: insights from model organisms. Cell, 1996, 86, 521-529.
85. Kelly, D.E.; Lamb, D.C.; Kelly, S.L. Genome-wide generation of yeast gene deletion strains. Comp. Funct. Genomics, 2001, 2, 236-242.
86. Que, Q.Q.; Winzeler, E.A. Large-scale mutagenesis and functional genomics in yeast. Funct. Integr. Genomics, 2002, 2, 193-198.
87. Giaever, G.; Chu, A.M.; Ni, L.; Connelly, C.; Riles, L.; Veronneau, S.; Dow, S.; Lucau-Danila, A.; Anderson, K.; Andre, B.; Arkin, A.P.; Astromoff, A.; El-Bakkoury, M.; Bangham, R.; Benito, R.; Brachat, S.; Campanaro, S.; Curtiss, M.; Davis, K.; Deutschbauer, A.; Entian, K.D.; Flaherty, P.; Foury, F.; Garfinkel, D.J.; Gerstein, M.; Gotte, D.; Guldener, U.; Hegemann, J.H.; Hempel, S.; Herman, Z.; Jaramillo, D.F.; Kelly, D.E.; Kelly, S.L.; Kotter, P.; LaBonte, D.; Lamb, D.C.; Lan, N.; Liang, H.; Liao, H.; Liu, L.; Luo, C.; Lussier, M.; Mao, R.; Menard, P.; Ooi, S.L.; Revuelta, J.L.; Roberts, C.J.; Rose, M.; Ross-Macdonald, P.; Scherens, B.; Schimmack, G.; Shafer, B.; Shoemaker, D.D.; Sookhai-Mahadeo, S.; Storms, R.K.; Strathern, J.N.; Valle, G.; Voet, M.; Volckaert, G.; Wang, C.Y.; Ward, T.R.; Wilhelmy, J.; Winzeler, E.A.; Yang, Y.; Yen, G.; Youngman, E.; Yu, K.; Bussey, H.; Boeke, J.D.; Snyder, M.; Philippsen, P.; Davis, R.W.; Johnston, M. Functional profiling of the Saccharomyces cerevisiae genome. Nature, 2002, 418, 387-391.
88. Costanzo, M.; Baryshnikova, A.; Bellay, J.; Kim, Y.; Spear, E.D.; Sevier, C.S.; Ding, H.; Koh, J.L.; Toufighi, K.; Mostafavi, S.; Prinz, J.; St Onge, R.P.; VanderSluis, B.; Makhnevych, T.; Vizeacoumar, F.J.; Alizadeh, S.; Bahr, S.; Brost, R.L.; Chen, Y.; Cokol, M.; Deshpande, R.; Li, Z.; Lin, Z.Y.; Liang, W.; Marback, M.; Paw, J.; San Luis, B.J.; Shuteriqi, E.; Tong, A.H.; van Dyk, N.; Wallace, I.M.; Whitney, J.A.; Weirauch, M.T.; Zhong, G.; Zhu, H.; Houry, W.A.; Brudno, M.; Ragibizadeh, S.; Papp, B.; Pal, C.; Roth, F.P.; Giaever, G.; Nislow, C.; Troyanskaya, O.G.; Bussey, H.; Bader, G.D.; Gingras, A.C.; Morris, Q.D.; Kim, P.M.; Kaiser, C.A.; Myers, C.L.; Andrews, B.J.; Boone, C. The genetic landscape of a cell. Science, 2010, 327, 425-431.
89. Adams, M.D.; Celniker, S.E.; Holt, R.A.; Evans, C.A.; Gocayne, J.D.; Amanatides, P.G.; Scherer, S.E.; Li, P.W.; Hoskins, R.A.; Galle, R.F.; George, R.A.; Lewis, S.E.; Richards, S.; Ashburner, M.; Henderson, S.N.; Sutton, G.G.; Wortman, J.R.; Yandell, M.D.; Zhang, Q.; Chen, L.X.; Brandon, R.C.; Rogers, Y.H.; Blazej, R.G.; Champe, M.; Pfeiffer, B.D.; Wan, K.H.; Doyle, C.; Baxter, E.G.; Helt, G.; Nelson, C.R.; Gabor, G.L.; Abril, J.F.; Agbayani, A.; An, H.J.; Andrews-Pfannkoch, C.; Baldwin, D.; Ballew, R.M.; Basu, A.; Baxendale, J.; Bayraktaroglu, L.; Beasley, E.M.; Beeson, K.Y.; Benos, P.V.; Berman, B.P.; Bhandari, D.; Bolshakov, S.; Borkova, D.; Botchan, M.R.; Bouck, J.; Brokstein, P.; Brottier, P.; Burtis, K.C.; Busam, D.A.; Butler, H.; Cadieu, E.; Center, A.; Chandra, I.; Cherry, J.M.; Cawley, S.; Dahlke, C.; Davenport, L.B.; Davies, P.; de Pablos, B.; Delcher, A.; Deng, Z.; Mays, A.D.; Dew, I.; Dietz, S.M.; Dodson, K.; Doup, L.E.; Downes, M.; Dugan-Rocha, S.; Dunkov, B.C.; Dunn, P.; Durbin, K.J.; Evangelista, C.C.; Ferraz, C.; Ferriera, S.; Fleischmann, W.; Fosler, C.; Gabrielian, A.E.; Garg, N.S.; Gelbart, W.M.; Glasser, K.; Glodek, A.; Gong, F.; Gorrell, J.H.; Gu, Z.; Guan, P.; Harris, M.; Harris, N.L.; Harvey, D.; Heiman, T.J.; Hernandez, J.R.; Houck, J.; Hostin, D.; Houston, K.A.; Howland, T.J.; Wei, M.H.; Ibegwam, C.; Jalali, M.; Kalush, F.; Karpen, G.H.; Ke, Z.; Kennison, J.A.; Ketchum, K.A.; Kimmel, B.E.; Kodira, C.D.; Kraft, C.; Kravitz, S.; Kulp, D.; Lai, Z.; Lasko, P.; Lei, Y.; Levitsky, A.A.; Li, J.; Li, Z.; Liang, Y.; Lin, X.; Liu, X.; Mattei, B.; McIntosh, T.C.; McLeod, M.P.; McPherson, D.; Merkulov, G.; Milshina, N.V.; Mobarry, C.; Morris, J.; Moshrefi, A.; Mount, S.M.; Moy, M.; Murphy, B.; Murphy, L.; Muzny, D.M.; Nelson, D.L.; Nelson, D.R.; Nelson, K.A.; Nixon, K.; Nusskern, D.R.; Pacleb, J.M.; Palazzolo, M.; Pittman, G.S.; Pan, S.; Pollard, J.; Puri, V.; Reese, M.G.; Reinert, K.; Remington, K.; Saunders, R.D.; Scheeler, F.; Shen, H.; Shue, B.C.; Siden-Kiamos, I.; Simpson, M.; Skupski, M.P.; Smith, T.; Spier, E.; Spradling, A.C.; Stapleton, M.; Strong, R.; Sun, E.; Svirskas, R.; Tector, C.; Turner, R.; Venter, E.; Wang, A.H.; Wang, X.; Wang, Z.Y.; Wassarman D.A.; Weinstock, G.M.; Weissenbach, J.; Williams, S.M.; WoodageT; Worley, K.C.; Wu, D.; Yang, S.; Yao, Q.A.; Ye, J.; Yeh, R.F.; Zaveri, J.S.; Zhan, M.; Zhang, G.; Zhao, Q.; Zheng, L.; Zheng, X.H.; Zhong, F.N.; Zhong, W.; Zhou, X.; Zhu, S.; Zhu, X.; Smith, H.O.; Gibbs, R.A.; Myers, E.W.; Rubin, G.M.; Venter, J.C. The genome sequence of Drosophila melanogaster. Science, 2000, 287, 2185-2195.
90. Liu, C.P.; Lim, J.K. Complementation analysis of methyl methanesulfonate-induced recessive lethal mutations in the zeste-white region of the X chromosome of Drosophila melanogaster. Genetics, 1975, 79, 601-611.
91. Lim, J.K.; Snyder, L.A. Cytogenetic and complementation analyses of recessive lethal mutations induced in the X chromosome of Drosophila by three alkylating agents. Genet. Res., 1974, 24, 1-10.
92. Ashburner, M.; Misra, S.; Roote, J.; Lewis, S.E.; Blazej, R.; Davis, T.; Doyle, C.; Galle, R.; George, R.; Harris, N.; Hartzell, G.; Harvey, D.; Hong, L.; Houston, K.; Hoskins, R.; Johnson, G.; Martin, C.; Moshrefi, A.; Palazzolo, M.; Reese, M.G.; Spradling, A.; Tsang, G.; Wan, K.; Whitelaw, K.; Celniker, S.; et al. An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region. Genetics, 1999, 153, 179-219.
93. Cooley, L.; Kelley, R.; Spradling, A. Insertional mutagenesis of the Drosophila genome with single P elements. Science, 1988, 239, 1121-1128.
94. Myrick, K.V.; Huet, F.; Mohr, S.E.; Alvarez-Garcia, I.; Lu, J.T.; Smith, M.A.; Crosby, M.A.; Gelbart, W.M. Large-scale functional annotation and expanded implementations of the P{wHy} hybrid transposon in the Drosophila melanogaster genome. Genetics, 2009, 182, 653-660.
95. Hacker, U.; Nystedt, S.; Barmchi, M.P.; Horn, C.; Wimmer, E.A. piggyBac-based insertional mutagenesis in the presence of stably integrated P elements in Drosophila. Proc. Natl. Acad. Sci. USA, 2003, 100, 7720-7725.
96. Thibault, S.T.; Singer, M.A.; Miyazaki, W.Y.; Milash, B.; Dompe, N.A.; Singh, C.M.; Buchholz, R.; Demsky, M.; Fawcett, R.; Francis-Lang, H.L.; Ryner, L.; Cheung, L.M.; Chong, A.; Erickson, C.; Fisher, W.W.; Greer, K.; Hartouni, S.R.; Howie, E.; Jakkula, L.; Joo, D.; Killpack, K.; Laufer, A.; Mazzotta, J.; Smith, R.D.; Stevens, L.M.; Stuber, C.; Tan, L.R.; Ventura, R.; Woo, A.; Zakrajsek, I.; Zhao, L.; Chen, F.; Swimmer, C.; Kopczynski, C.; Duyk, G.; Winberg, M.L.; Margolis, J. A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac. Nat. Genet., 2004, 36, 283-287.
97. St Johnston, D. The art and design of genetic screens: Drosophila melanogaster. Nat. Rev. Genet., 2002, 3, 176-188.
98. Ryder, E.; Russell, S. Transposable elements as tools for genomics and genetics in Drosophila. Brief Funct. Genomic Proteomic., 2003, 2, 57-71.
99. Sulston, J.E.; Albertson, D.G.; Thomson, J.N. The Caenorhabditis elegans male: postembryonic development of nongonadal structures. Dev. Biol., 1980, 78, 542-576.
100. Sulston, J.E.; Schierenberg, E.; White, J.G.; Thomson, J.N. The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev. Biol., 1983, 100, 64-119.
101. Hillier, L.W.; Coulson, A.; Murray, J.I.; Bao, Z.; Sulston, J.E.; Waterston, R.H. Genomics in C. elegans: so many genes, such a little worm. Genome Res., 2005, 15, 1651-1660.
102. Granger, L.; Martin, E.; Segalat, L. Mos as a tool for genome-wide insertional mutagenesis in Caenorhabditis elegans: results of a pilot study. Nucleic Acids Res., 2004, 32, e117.
103. Montgomery, M.K.; Fire, A. Double-stranded RNA as a mediator in sequence-specific genetic silencing and co-suppression. Trends Genet., 1998, 14, 255-258.
104. Fraser, A.G.; Kamath, R.S.; Zipperlen, P.; Martinez-Campos, M.; Sohrmann, M.; Ahringer, J. Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature, 2000, 408, 325-330.
105. Kamath, R.S.; Fraser, A.G.; Dong, Y.; Poulin, G.; Durbin, R.; Gotta, M.; Kanapin, A.; Le Bot, N.; Moreno, S.; Sohrmann, M.; Welchman, D.P.; Zipperlen, P.; Ahringer, J. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature, 2003, 421, 231-237.
106. Alessandrini, F.; Jakob, T.; Wolf, A.; Wolf, E.; Balling, R.; Hrabe de Angelis, M.; Ring, J.; Behrendt, H. Enu mouse mutagenesis: generation of mouse mutants with aberrant plasma IgE levels. Int. Arch. Allergy Immunol., 2001, 124, 25-28.
107. Barbaric, I.; Wells, S.; Russ, A.; Dear, T.N. Spectrum of ENUinduced mutations in phenotype-driven and gene-driven screens in the mouse. Environ. Mol. Mutagen., 2007, 48, 124-142.
108. Boles, M.K.; Wilkinson, B.M.; Wilming, L.G.; Liu, B.; Probst, F.J.; Harrow, J.; Grafham, D.; Hentges, K.E.; Woodward, L.P.; Maxwell, A.; Mitchell, K.; Risley, M.D.; Johnson, R.; Hirschi, K.; Lupski, J.R.; Funato, Y.; Miki, H.; Marin-Garcia, P.; Matthews, L.; Coffey, A.J.; Parker, A.; Hubbard, T.J.; Rogers, J.; Bradley, A.; Adams, D.J.; Justice, M.J. Discovery of candidate disease genes in ENU-induced mouse mutants by large-scale sequencing, including a splice-site mutation in nucleoredoxin. PLoS Genet., 2009, 5, e1000759.
109. Brown, S.D.; Balling, R. Systematic approaches to mouse mutagenesis. Curr. Opin. Genet. Dev., 2001, 11, 268-273.
110. Clark, A.T.; Goldowitz, D.; Takahashi, J.S.; Vitaterna, M.H.; Siepka, S.M.; Peters, L.L.; Frankel, W.N.; Carlson, G.A.; Rossant, J.; Nadeau, J.H.; Justice, M.J. Implementing large-scale ENU mutagenesis screens in North America. Genetica, 2004, 122, 51-64.
111. Cordes, S.P. N-ethyl-N-nitrosourea mutagenesis: boarding themouse mutant express. Microbiol. Mol. Biol. Rev., 2005, 69, 426-439.
112. Hrabe de Angelis, M.; Balling, R. Large scale ENU screens in the mouse: genetics meets genomics. Mutat. Res., 1998, 400, 25-32.
113. Hrabe de Angelis, M.; Strivens, M. Large-scale production of mouse phenotypes: the search for animal models for inherited diseases in humans. Brief Bioinform., 2001, 2, 170-180.
114. Hrabe de Angelis, M.H.; Flaswinkel, H.; Fuchs, H.; Rathkolb, B.; Soewarto, D.; Marschall, S.; Heffner, S.; Pargent, W.; Wuensch, K.; Jung, M.; Reis, A.; Richter, T.; Alessandrini, F.; Jakob, T.; Fuchs, E.; Kolb, H.; Kremmer, E.; Schaeble, K.; Rollinski, B.; Roscher, A.; Peters, C.; Meitinger, T.; Strom, T.; Steckler, T.; Holsboer, F.; Klopstock, T.; Gekeler, F.; Schindewolf, C.; Jung, T.; Avraham, K.; Behrendt, H.; Ring, J.; Zimmer, A.; Schughart, K.; Pfeffer, K.; Wolf, E.; Balling, R. Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nat. Genet., 2000, 25, 444-447.
115. Nishimura, I.; Drake, T.A.; Lusis, A.J.; Lyons, K.M.; Nadeau, J.H.; Zernik, J. ENU large-scale mutagenesis and quantitative trait linkage (QTL) analysis in mice: novel technologies for searching polygenetic determinants of craniofacial abnormalities. Crit. Rev. Oral. Biol. Med., 2003, 14, 320-330.
116. Nolan, P.M.; Peters, J.; Vizor, L.; Strivens, M.; Washbourne, R.; Hough, T.; Wells, C.; Glenister, P.; Thornton, C.; Martin, J.; Fisher, E.; Rogers, D.; Hagan, J.; Reavill, C.; Gray, I.; Wood, J.; Spurr, N.; Browne, M.; Rastan, S.; Hunter, J.; Brown, S.D. Implementation of a large-scale ENU mutagenesis program: towards increasing the mouse mutant resource. Mamm. Genome, 2000, 11, 500-506.
117. Rathkolb, B.; Fuchs, E.; Kolb, H.J.; Renner-Muller, I.; Krebs, O.; Balling, R.; Hrabe de Angelis, M.; Wolf, E. Large-scale N-ethyl-Nnitrosourea mutagenesis of mice--from phenotypes to genes. Exp. Physiol., 2000, 85, 635-644.
118. Sakuraba, Y.; Sezutsu, H.; Takahasi, K.R.; Tsuchihashi, K.; Ichikawa, R.; Fujimoto, N.; Kaneko, S.; Nakai, Y.; Uchiyama, M.; Goda, N.; Motoi, R.; Ikeda, A.; Karashima, Y.; Inoue, M.; Kaneda, H.; Masuya, H.; Minowa, O.; Noguchi, H.; Toyoda, A.; Sakaki, Y.; Wakana, S.; Noda, T.; Shiroishi, T.; Gondo, Y. Molecular characterization of ENU mouse mutagenesis and archives. Biochem. Biophys. Res. Commun., 2005, 336, 609-616.
119. Soewarto, D.; Fella, C.; Teubner, A.; Rathkolb, B.; Pargent, W.; Heffner, S.; Marschall, S.; Wolf, E.; Balling, R.; Hrabe de Angelis, M. The large-scale Munich ENU-mouse-mutagenesis screen. Mamm. Genome, 2000, 11, 507-510.
120. Stanford, W.L.; Cohn, J.B.; Cordes, S.P. Gene-trap mutagenesis: past, present and beyond. Nat. Rev. Genet., 2001, 2, 756-768.
121. Araki, M.; Araki, K.; Yamamura, K. International Gene Trap Project: towards gene-driven saturation mutagenesis in mice. Curr. Pharm. Biotechnol., 2009, 10, 221-229.
122. Guan, C.; Ye, C.; Yang, X.; Gao, J. A review of current large-scale mouse knockout efforts. Genesis, 2010, 48, 73-85.
123. Nord, A.S.; Chang, P.J.; Conklin, B.R.; Cox, A.V.; Harper, C.A.; Hicks, G.G.; Huang, C.C.; Johns, S.J.; Kawamoto, M.; Liu, S.; Meng, E.C.; Morris, J.H.; Rossant, J.; Ruiz, P.; Skarnes, W.C.; Soriano, P.; Stanford, W.L.; Stryke, D.; von Melchner, H.; Wurst, W.; Yamamura, K.; Young, S.G.; Babbitt, P.C.; Ferrin, T.E. The International Gene Trap Consortium Website: a portal to all publicly available gene trap cell lines in mouse. Nucleic Acids Res., 2006, 34, D642-8.
124. Skarnes, W.C.; von Melchner, H.; Wurst, W.; Hicks, G.; Nord, A.S.; Cox, T.; Young, S.G.; Ruiz, P.; Soriano, P.; Tessier-Lavigne, M.; Conklin, B.R.; Stanford, W.L.; Rossant, J. A public gene trap resource for mouse functional genomics. Nat. Genet., 2004, 36, 543-544.
125. Stanford, W.L.; Epp, T.; Reid, T.; Rossant, J. Gene trapping in embryonic stem cells. Methods Enzymol., 2006, 420, 136-162.
126. Brandon, E.P.; Idzerda, R.L.; McKnight, G.S. Targeting the mouse genome: a compendium of knockouts (Part III). Curr. Biol., 1995, 5, 873-881.
127. Brandon, E.P.; Idzerda, R.L.; McKnight, G.S. Targeting the mouse genome: a compendium of knockouts (Part II). Curr. Biol., 1995, 5, 758-765.
128. Brandon, E.P.; Idzerda, R.L.; McKnight, G.S. Knockouts. Targeting the mouse genome: a compendium of knockouts (Part I). Curr. Biol., 1995, 5, 625-634.
129. Hurst, L.D.; Smith, N.G. Do essential genes evolve slowly? Curr. Biol. 1999, 9, 747-750.
130. Zambrowicz, B.P.; Sands, A.T. Knockouts model the 100 bestselling drugs--will they model the next 100? Nat. Rev. Drug Discov., 2003, 2, 38-51.
131. Leroux, L.; Desbois, P.; Lamotte, L.; Duvillie, B.; Cordonnier, N.; Jackerott, M.; Jami, J.; Bucchini, D.; Joshi, R.L. Compensatory responses in mice carrying a null mutation for Ins1 or Ins2. Diabetes, 2001, 50(Suppl 1), S150-3.
132. Duvillie, B.; Cordonnier, N.; Deltour, L.; Dandoy-Dron, F.; Itier, J.M.; Monthioux, E.; Jami, J.; Joshi, R.L.; Bucchini, D. Phenotypic alterations in insulin-deficient mutant mice. Proc. Natl. Acad. Sci. USA, 1997, 94, 5137-5140.
133. Joshi, R.L.; Lamothe, B.; Cordonnier, N.; Mesbah, K.; Monthioux, E.; Jami, J.; Bucchini, D. Targeted disruption of the insulin receptor gene in the mouse results in neonatal lethality. EMBO J., 1996, 15, 1542-1547.
134. Accili, D.; Drago, J.; Lee, E.J.; Johnson, M.D.; Cool, M.H.; Salvatore, P.; Asico, L.D.; Jose, P.A.; Taylor, S.I.; Westphal, H. Early neonatal death in mice homozygous for a null allele of the insulin receptor gene. Nat. Genet., 1996, 12, 106-109.
135. Mullins, M.C.; Hammerschmidt, M.; Haffter, P.; Nusslein-Volhard, C. Large-scale mutagenesis in the zebrafish: in search of genes controlling development in a vertebrate. Curr. Biol., 1994, 4, 189-202.
136. Haffter, P.; Nusslein-Volhard, C. Large scale genetics in a small vertebrate, the zebrafish. Int. J. Dev. Biol., 1996, 40, 221-227.
137. Geisler, R.; Rauch, G.J.; Geiger-Rudolph, S.; Albrecht, A.; van Bebber, F.; Berger, A.; Busch-Nentwich, E.; Dahm, R.; Dekens, M.P.; Dooley, C.; Elli, A.F.; Gehring, I.; Geiger, H.; Geisler, M.; Glaser, S.; Holley, S.; Huber, M.; Kerr, A.; Kirn, A.; Knirsch, M.; Konantz, M.; Kuchler, A.M.; Maderspacher, F.; Neuhauss, S.C.; Nicolson, T.; Ober, E.A.; Praeg, E.; Ray, R.; Rentzsch, B.; Rick, J.M.; Rief, E.; Schauerte, H.E.; Schepp, C.P.; Schonberger, U.; Schonthaler, H.B.; Seiler, C.; Sidi, S.; Sollner, C.; Wehner, A.; Weiler, C.; Nusslein-Volhard, C. Large-scale mapping of mutations affecting zebrafish development. BMC Genomics, 2007, 8, 11.
138. de Bruijn, E.; Cuppen, E.; Feitsma, H. Highly Efficient ENU Mutagenesis in Zebrafish. Methods Mol. Biol., 2009, 546, 3-12.
139. Draper, B.W.; McCallum, C.M.; Stout, J.L.; Slade, A.J.; Moens, C.B. A high-throughput method for identifying N-ethyl-Nnitrosourea (ENU)-induced point mutations in zebrafish. Methods Cell Biol., 2004, 77, 91-112.
140. Grunwald, D.J.; Streisinger, G. Induction of recessive lethal and specific locus mutations in the zebrafish with ethyl nitrosourea. Genet. Res., 1992, 59, 103-116.
141. Sood, R.; English, M.A.; Jones, M.; Mullikin, J.; Wang, D.M.; Anderson, M.; Wu, D.; Chandrasekharappa, S.C.; Yu, J.; Zhang, J.; Paul Liu, P. Methods for reverse genetic screening in zebrafish by resequencing and TILLING. Methods, 2006, 39, 220-227.
142. Henikoff, S.; Till, B.J.; Comai, L. TILLING. Traditional mutagenesis meets functional genomics. Plant Physiol., 2004, 135, 630-636.
143. Moens, C.B.; Donn, T.M.; Wolf-Saxon, E.R.; Ma, T.P. Reverse genetics in zebrafish by TILLING. Brief Funct. Genomic. Proteomic., 2008, 7, 454-459.
144. Nasevicius, A.; Ekker, S.C. Effective targeted gene 'knockdown' in zebrafish. Nat. Genet., 2000, 26, 216-220.
145. George, R.A.; Smith, T.D.; Callaghan, S.; Hardman, L.; Pierides, C.; Horaitis, O.; Wouters, M.A.; Cotton, R.G. General mutation databases: analysis and review. J. Med. Genet., 2008, 45, 65-70.
146. Hamosh, A.; Scott, A.F.; Amberger, J.; Valle, D.; McKusick, V.A. Online Mendelian Inheritance in Man (OMIM). Hum. Mutat., 2000, 15, 57-61.
147. Amberger, J.; Bocchini, C.A.; Scott, A.F.; Hamosh, A. McKusick's Online Mendelian Inheritance in Man (OMIM). Nucleic Acids Res., 2009, 37, D793-6.
148. Stenson, P.D.; Mort, M.; Ball, E.V.; Howells, K.; Phillips, A.D.; Thomas, N.S.; Cooper, D.N. The Human Gene Mutation Database: 2008 update. Genome Med., 2009, 1, 13.
149. Cooper, D.N.; Chen, J.M.; Ball, E.V.; Howells, K.; Mort, M.; Phillips, A.D.; Chuzhanova, N.; Krawczak, M.; Kehrer-Sawatzki, H.; Stenson, P.D. Genes, mutations, and human inherited disease at the dawn of the age of personalized genomics. Hum. Mutat., 2010, 31, 631-655.
150. Ring, H.Z.; Kwok, P.Y.; Cotton, R.G. Human Variome Project: an international collaboration to catalogue human genetic variation. Pharmacogenomics, 2006, 7, 969-972.
151. Fredman, D.; Munns, G.; Rios, D.; Sjoholm, F.; Siegfried, M.; Lenhard, B.; Lehvaslaiho, H.; Brookes, A.J. HGVbase: a curated resource describing human DNA variation and phenotype relationships. Nucleic Acids Res., 2004, 32, D516-9.
152. Drake, J.W.; Charlesworth, B.; Charlesworth, D.; Crow, J.F. Rates of spontaneous mutation. Genetics, 1998, 148, 1667-1686.
153. Nachman, M.W.; Crowell, S.L. Estimate of the mutation rate per nucleotide in humans. Genetics, 2000, 156, 297-304.
154. Xue, Y.; Wang, Q.; Long, Q.; Ng, B.L.; Swerdlow, H.; Burton, J.; Skuce, C.; Taylor, R.; Abdellah, Z.; Zhao, Y.; MacArthur, D.G.; Quail, M.A.; Carter, N.P.; Yang, H.; Tyler-Smith, C. Human Y chromosome base-substitution mutation rate measured by direct sequencing in a deep-rooting pedigree. Curr. Biol., 2009, 19, 1453-1457.
155. Roach, J.C.; Glusman, G.; Smit, A.F.; Huff, C.D.; Hubley, R.; Shannon, P.T.; Rowen, L.; Pant, K.P.; Goodman, N.; Bamshad, M.; Shendure, J.; Drmanac, R.; Jorde, L.B.; Hood, L.; Galas, D.J. Analysis of genetic inheritance in a family quartet by wholegenome sequencing. Science, 2010, 328, 636-639.
156. Carson, A.R.; Feuk, L.; Mohammed, M.; Scherer, S.W. Strategies for the detection of copy number and other structural variants in the human genome. Hum. Genomics, 2006, 2, 403-414.
157. Feuk, L.; Carson, A.R.; Scherer, S.W. Structural variation in the human genome. Nat. Rev. Genet., 2006, 7, 85-97.
158. Pinto, D.; Marshall, C.; Feuk, L.; Scherer, S.W. Copy-number variation in control population cohorts. Hum. Mol. Genet., 2007, 16 Spec No. 2, R168-73.
159. Kumar, D. Disorders of the genome architecture: a review. Genomic Med., 2008, 2, 69-76.
160. Kryukov, G.V.; Pennacchio, L.A.; Sunyaev, S.R. Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. Am. J. Hum. Genet., 2007, 80, 727-739.
161. Sunyaev, S.; Ramensky, V.; Koch, I.; Lathe, W., 3rd; Kondrashov, A.S.; Bork, P. Prediction of deleterious human alleles. Hum. Mol. Genet., 2001, 10, 591-597.
162. Yampolsky, L.Y.; Kondrashov, F.A.; Kondrashov, A.S. Distribution of the strength of selection against amino acid replacements in human proteins. Hum. Mol. Genet., 2005, 14, 3191-3201.
163. Boyko, A.R.; Williamson, S.H.; Indap, A.R.; Degenhardt, J.D.; Hernandez, R.D.; Lohmueller, K.E.; Adams, M.D.; Schmidt, S.; Sninsky, J.J.; Sunyaev, S.R.; White, T.J.; Nielsen, R.; Clark, A.G.; Bustamante, C.D. Assessing the evolutionary impact of amino acid mutations in the human genome. PLoS Genet., 2008, 4, e1000083.
164. Eyre-Walker, A.; Keightley, P.D. High genomic deleterious mutation rates in hominids. Nature, 1999, 397, 344-347.
165. Kondrashov, A.S. Direct estimates of human per nucleotide mutation rates at 20 loci causing Mendelian diseases. Hum. Mutat., 2003, 21, 12-27.
166. Population Reference Bureau. World Population Data Sheet. 2009.
167. Sankaranarayanan, K. Ionizing radiation and genetic risks IX. Estimates of the frequencies of mendelian diseases and spontaneous mutation rates in human populations: a 1998 perspective. Mutat. Res., 1998, 411, 129-178.
168. Wilkie, A.O. The molecular basis of genetic dominance. J. Med. Genet., 1994, 31, 89-98.
169. Frank, T.S.; Deffenbaugh, A.M.; Reid, J.E.; Hulick, M.; Ward, B.E.; Lingenfelter, B.; Gumpper, K.L.; Scholl, T.; Tavtigian, S.V.; Pruss, D.R.; Critchfield, G.C. Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J. Clin. Oncol., 2002, 20, 1480-1490.
170. Delatycki, M.B.; Williamson, R.; Forrest, S.M. Friedreich ataxia: an overview. J. Med. Genet., 2000, 37, 1-8.
171. Vucic, S.; Kiernan, M.C. Pathophysiology of neurodegeneration in familial amyotrophic lateral sclerosis. Curr. Mol. Med., 2009, 9, 255-272.
172. Julien, J.P.; Kriz, J. Transgenic mouse models of amyotrophic lateral sclerosis. Biochim. Biophys. Acta, 2006, 1762, 1013-1024.
173. Abifadel, M.; Rabes, J.P.; Devillers, M.; Munnich, A.; Erlich, D.; Junien, C.; Varret, M.; Boileau, C. Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease. Hum. Mutat., 2009, 30, 520-529.
174. Soutar, A.K.; Naoumova, R.P. Mechanisms of disease: genetic causes of familial hypercholesterolemia. Nat. Clin. Pract. Cardiovasc. Med., 2007, 4, 214-225.
175. Horton, J.D.; Cohen, J.C.; Hobbs, H.H. Molecular biology of PCSK9: its role in LDL metabolism. Trends Biochem. Sci., 2007, 32, 71-77.
176. Rahalkar, A.R.; Hegele, R.A. Monogenic pediatric dyslipidemias: classification, genetics and clinical spectrum. Mol. Genet. Metab., 2008, 93, 282-294.
177. Tarugi, P.; Averna, M.; Di Leo, E.; Cefalu, A.B.; Noto, D.; Magnolo, L.; Cattin, L.; Bertolini, S.; Calandra, S. Molecular diagnosis of hypobetalipoproteinemia: an ENID review. Atherosclerosis, 2007, 195, e19-27.
178. Whitfield, A.J.; Barrett, P.H.; van Bockxmeer, F.M.; Burnett, J.R. Lipid disorders and mutations in the APOB gene. Clin. Chem., 2004, 50, 1725-1732.
179. Farese, R.V., Jr.; Linton, M.F.; Young, S.G. Apolipoprotein B gene mutations affecting cholesterol levels. J. Intern. Med., 1992, 231, 643-652.
180. Varret, M.; Abifadel, M.; Rabes, J.P.; Boileau, C. Genetic heterogeneity of autosomal dominant hypercholesterolemia. Clin. Genet., 2008, 73, 1-13.
181. Phadnis, N.; Fry, J.D. Widespread correlations between dominance and homozygous effects of mutations: implications for theories of dominance. Genetics, 2005, 171, 385-392.
182. Porteous, J.W. Dominance--one hundred and fifteen years after Mendel's paper. J. Theor. Biol., 1996, 182, 223-232.
183. Wright, S. Physiological and evolutionary theories of dominance. Am. Nat., 1934, 68, 24-53.
184. Kacser, H.; Burns, J.A. The control of flux. Symp. Soc. Exp. Biol., 1973, 27, 65-104.
185. Kacser, H.; Burns, J.A. The molecular basis of dominance. Genetics, 1981, 97, 639-666.
186. Grossniklaus, U.; Madhusudhan, M.S.; Nanjundiah, V. Nonlinear enzyme kinetics can lead to high metabolic flux control coefficients: implications for the evolution of dominance. J. Theor. Biol., 1996, 182, 299-302.
187. Bagheri, H.C.; Wagner, G.P. Evolution of dominance in metabolic pathways. Genetics, 2004, 168, 1713-1735.
188. Orr, H.A. A test of Fisher's theory of dominance. Proc. Natl. Acad. Sci. USA, 1991, 88, 11413-11415.
189. Charrow, J. Ashkenazi Jewish genetic disorders. Fam. Cancer, 2004, 3, 201-206.
190. Boycott, K.M.; Parboosingh, J.S.; Chodirker, B.N.; Lowry, R.B.; McLeod, D.R.; Morris, J.; Greenberg, C.R.; Chudley, A.E.; Bernier, F.P.; Midgley, J.; Moller, L.B.; Innes, A.M. Clinical genetics and the Hutterite population: a review of Mendelian disorders. Am. J. Med. Genet. A, 2008, 146A, 1088-1098.
191. Laberge, A.M.; Michaud, J.; Richter, A.; Lemyre, E.; Lambert, M.; Brais, B.; Mitchell, G.A. Population history and its impact on medical genetics in Quebec. Clin. Genet., 2005, 68, 287-301.
192. Peltonen, L.; Jalanko, A.; Varilo, T. Molecular genetics of the Finnish disease heritage. Hum. Mol. Genet., 1999, 8, 1913-1923.
193. Zlotogora, J.; Shalev, S.; Habiballah, H.; Barjes, S. Genetic disorders among Palestinian Arabs: 3. Autosomal recessive disorders in a single village. Am. J. Med. Genet., 2000, 92, 343-345.
194. Hassold, T.; Chen, N.; Funkhouser, J.; Jooss, T.; Manuel, B.; Matsuura, J.; Matsuyama, A.; Wilson, C.; Yamane, J.A.; Jacobs, P.A. A cytogenetic study of 1000 spontaneous abortions. Ann. Hum. Genet., 1980, 44, 151-178.
195. Philipp, T.; Philipp, K.; Reiner, A.; Beer, F.; Kalousek, D.K. Embryoscopic and cytogenetic analysis of 233 missed abortions: factors involved in the pathogenesis of developmental defects of early failed pregnancies. Hum. Reprod., 2003, 18, 1724-1732.
196. Schaeffer, A.J.; Chung, J.; Heretis, K.; Wong, A.; Ledbetter, D.H.; Lese Martin, C. Comparative genomic hybridization-array analysis enhances the detection of aneuploidies and submicroscopic imbalances in spontaneous miscarriages. Am. J. Hum. Genet., 2004, 74, 1168-1174.
197. Kosaki, K.; Kosaki, R.; Suzuki, T.; Yoshihashi, H.; Takahashi, T.; Sasaki, K.; Tomita, M.; McGinnis, W.; Matsuo, N. Complete mutation analysis panel of the 39 human HOX genes. Teratology, 2002, 65, 50-62.
198. Bosley, T.M.; Alorainy, I.A.; Salih, M.A.; Aldhalaan, H.M.; Abu-Amero, K.K.; Oystreck, D.T.; Tischfield, M.A.; Engle, E.C.; Erickson, R.P. The clinical spectrum of homozygous HOXA1 mutations. Am. J. Med. Genet. A, 2008, 146A, 1235-1240.
199. Alasti, F.; Sadeghi, A.; Sanati, M.H.; Farhadi, M.; Stollar, E.; Somers, T.; Van Camp, G. A mutation in HOXA2 is responsible for autosomal-recessive microtia in an Iranian family. Am. J. Hum. Genet., 2008, 82, 982-991.
200. Horvat-Switzer, R.D.; Thompson, A.A. HOXA11 mutation in amegakaryocytic thrombocytopenia with radio-ulnar synostosis syndrome inhibits megakaryocytic differentiation in vitro. Blood Cells Mol. Dis., 2006, 37, 55-63.
201. Goodman, F.R.; Bacchelli, C.; Brady, A.F.; Brueton, L.A.; Fryns, J.P.; Mortlock, D.P.; Innis, J.W.; Holmes, L.B.; Donnenfeld, A.E.; Feingold, M.; Beemer, F.A.; Hennekam, R.C.; Scambler, P.J. Novel HOXA13 mutations and the phenotypic spectrum of handfoot-genital syndrome. Am. J. Hum. Genet., 2000, 67, 197-202.
202. Mortlock, D.P.; Innis, J.W. Mutation of HOXA13 in hand-footgenital syndrome. Nat. Genet., 1997, 15, 179-180.
203. Dobbs, M.B.; Gurnett, C.A.; Pierce, B.; Exner, G.U.; Robarge, J.; Morcuende, J.A.; Cole, W.G.; Templeton, P.A.; Foster, B.; Bowcock, A.M. HOXD10 M319K mutation in a family with isolated congenital vertical talus. J. Orthop. Res., 2006, 24, 448-453.
204. Shrimpton, A.E.; Levinsohn, E.M.; Yozawitz, J.M.; Packard, D.S., Jr.; Cady, R.B.; Middleton, F.A.; Persico, A.M.; Hootnick, D.R. A HOX gene mutation in a family with isolated congenital vertical talus and Charcot-Marie-Tooth disease. Am. J. Hum. Genet., 2004, 75, 92-96.
205. Muragaki, Y.; Mundlos, S.; Upton, J.; Olsen, B.R. Altered growth and branching patterns in synpolydactyly caused by mutations in HOXD13. Science, 1996, 272, 548-551.
206. Bentley, D.R. Whole-genome re-sequencing. Curr. Opin. Genet. Dev., 2006, 16, 545-552.
207. Levy, S.; Sutton, G.; Ng, P.C.; Feuk, L.; Halpern, A.L.; Walenz, B.P.; Axelrod, N.; Huang, J.; Kirkness, E.F.; Denisov, G.; Lin, Y.; MacDonald, J.R.; Pang, A.W.; Shago, M.; Stockwell, T.B.; Tsiamouri, A.; Bafna, V.; Bansal, V.; Kravitz, S.A.; Busam, D.A.; Beeson, K.Y.; McIntosh, T.C.; Remington, K.A.; Abril, J.F.; Gill, J.; Borman, J.; Rogers, Y.H.; Frazier, M.E.; Scherer, S.W.; Strausberg, R.L.; Venter, J.C. The diploid genome sequence of an individual human. PLoS Biol., 2007, 5, e254.
208. Kim, J.I.; Ju, Y.S.; Park, H.; Kim, S.; Lee, S.; Yi, J.H.; Mudge, J.; Miller, N.A.; Hong, D.; Bell, C.J.; Kim, H.S.; Chung, I.S.; Lee, W.C.; Lee, J.S.; Seo, S.H.; Yun, J.Y.; Woo, H.N.; Lee, H.; Suh, D.; Lee, S.; Kim, H.J.; Yavartanoo, M.; Kwak, M.; Zheng, Y.; Lee, M.K.; Park, H.; Kim, J.Y.; Gokcumen, O.; Mills, R.E.; Zaranek, A.W.; Thakuria, J.; Wu, X.; Kim, R.W.; Huntley, J.J.; Luo, S.; Schroth, G.P.; Wu, T.D.; Kim, H.; Yang, K.S.; Park, W.Y.; Kim, H.; Church, G.M.; Lee, C.; Kingsmore, S.F.; Seo, J.S. A highly annotated whole-genome sequence of a Korean individual. Nature, 2009, 460, 1011-1015.
209. McKernan, K.J.; Peckham, H.E.; Costa, G.L.; McLaughlin, S.F.; Fu, Y.; Tsung, E.F.; Clouser, C.R.; Duncan, C.; Ichikawa, J.K.; Lee, C.C.; Zhang, Z.; Ranade, S.S.; Dimalanta, E.T.; Hyland, F.C.; Sokolsky, T.D.; Zhang, L.; Sheridan, A.; Fu, H.; Hendrickson, C.L.; Li, B.; Kotler, L.; Stuart, J.R.; Malek, J.A.; Manning, J.M.; Antipova, A.A.; Perez, D.S.; Moore, M.P.; Hayashibara, K.C.; Lyons, M.R.; Beaudoin, R.E.; Coleman, B.E.; Laptewicz, M.W.; Sannicandro, A.E.; Rhodes, M.D.; Gottimukkala, R.K.; Yang, S.; Bafna, V.; Bashir, A.; MacBride, A.; Alkan, C.; Kidd, J.M.; Eichler, E.E.; Reese, M.G.; De La Vega, F.M.; Blanchard, A.P. Sequence and structural variation in a human genome uncovered by short-read, massively parallel ligation sequencing using two-base encoding. Genome Res., 2009, 19, 1527-1541.
210. Wang, J.; Wang, W.; Li, R.; Li, Y.; Tian, G.; Goodman, L.; Fan, W.; Zhang, J.; Li, J.; Zhang, J.; Guo, Y.; Feng, B.; Li, H.; Lu, Y.; Fang, X.; Liang, H.; Du, Z.; Li, D.; Zhao, Y.; Hu, Y.; Yang, Z.; Zheng, H.; Hellmann, I.; Inouye, M.; Pool, J.; Yi, X.; Zhao, J.; Duan, J.; Zhou, Y.; Qin, J.; Ma, L.; Li, G.; Yang, Z.; Zhang, G.; Yang, B.; Yu, C.; Liang, F.; Li, W.; Li, S.; Li, D.; Ni, P.; Ruan, J.; Li, Q.; Zhu, H.; Liu, D.; Lu, Z.; Li, N.; Guo, G.; Zhang, J.; Ye, J.; Fang, L.; Hao, Q.; Chen, Q.; Liang, Y.; Su, Y.; San, A.; Ping, C.; Yang, S.; Chen, F.; Li, L.; Zhou, K.; Zheng, H.; Ren, Y.; Yang, L.; Gao, Y.; Yang, G.; Li, Z.; Feng, X.; Kristiansen, K.; Wong, G.K.; Nielsen, R.; Durbin, R.; Bolund, L.; Zhang, X.; Li, S.; Yang, H.; Wang, J. The diploid genome sequence of an Asian individual. Nature, 2008, 456, 60-65.
211. Wheeler, D.A.; Srinivasan, M.; Egholm, M.; Shen, Y.; Chen, L.; McGuire, A.; He, W.; Chen, Y.J.; Makhijani, V.; Roth, G.T.; Gomes, X.; Tartaro, K.; Niazi, F.; Turcotte, C.L.; Irzyk, G.P.; Lupski, J.R.; Chinault, C.; Song, X.Z.; Liu, Y.; Yuan, Y.; Nazareth, L.; Qin, X.; Muzny, D.M.; Margulies, M.; Weinstock, G.M.; Gibbs, R.A.; Rothberg, J.M. The complete genome of an individual by massively parallel DNA sequencing. Nature, 2008, 452, 872-876.
212. Bentley, D.R.; Balasubramanian, S.; Swerdlow, H.P.; Smith, G.P.; Milton, J.; Brown, C.G.; Hall, K.P.; Evers, D.J.; Barnes, C.L.; Bignell, H.R.; Boutell, J.M.; Bryant, J.; Carter, R.J.; Keira Cheetham, R.; Cox, A.J.; Ellis, D.J.; Flatbush, M.R.; Gormley, N.A.; Humphray, S.J.; Irving, L.J.; Karbelashvili, M.S.; Kirk, S.M.; Li, H.; Liu, X.; Maisinger, K.S.; Murray, L.J.; Obradovic, B.; Ost, T.; Parkinson, M.L.; Pratt, M.R.; Rasolonjatovo, I.M.; Reed, M.T.; Rigatti, R.; Rodighiero, C.; Ross, M.T.; Sabot, A.; Sankar, S.V.; Scally, A.; Schroth, G.P.; Smith, M.E.; Smith, V.P.; Spiridou, A.; Torrance, P.E.; Tzonev, S.S.; Vermaas, E.H.; Walter, K.; Wu, X.; Zhang, L.; Alam, M.D.; Anastasi, C.; Aniebo, I.C.; Bailey, D.M.; Bancarz, I.R.; Banerjee, S.; Barbour, S.G.; Baybayan, P.A.; Benoit, V.A.; Benson, K.F.; Bevis, C.; Black, P.J.; Boodhun, A.; Brennan, J.S.; Bridgham, J.A.; Brown, R.C.; Brown, A.A.; Buermann, D.H.; Bundu, A.A.; Burrows, J.C.; Carter, N.P.; Castillo, N.; Chiara, E.C.M.; Chang, S.; Neil Cooley, R.; Crake, N.R.; Dada, O.O.; Diakoumakos, K.D.; Dominguez-Fernandez, B.; Earnshaw, D.J.; Egbujor, U.C.; Elmore, D.W.; Etchin, S.S.; Ewan, M.R.; Fedurco, M.; Fraser, L.J.; Fuentes Fajardo, K.V.; Scott Furey, W.; George, D.; Gietzen, K.J.; Goddard, C.P.; Golda, G.S.; Granieri, P.A.; Green, D.E.; Gustafson, D.L.; Hansen, N.F.; Harnish, K.; Haudenschild, C.D.; Heyer, N.I.; Hims, M.M.; Ho, J.T.; Horgan, A.M.; Hoschler, K.; Hurwitz, S.; Ivanov, D.V.; Johnson, M.Q.; James, T.; Huw Jones, T.A.; Kang, G.D.; Kerelska, T.H.; Kersey, A.D.; Khrebtukova, I.; Kindwall, A.P.; Kingsbury, Z.; Kokko-Gonzales, P.I.; Kumar, A.; Laurent, M.A.; Lawley, C.T.; Lee, S.E.; Lee, X.; Liao, A.K.; Loch, J.A.; Lok, M.; Luo, S.; Mammen, R.M.; Martin, J.W.; McCauley, P.G.; McNitt, P.; Mehta, P.; Moon, K.W.; Mullens, J.W.; Newington, T.; Ning, Z.; Ling Ng, B.; Novo, S.M.; O'Neill, M.J.; Osborne, M.A.; Osnowski, A.; Ostadan, O.; Paraschos, L.L.; Pickering, L.; Pike, A.C.; Pike, A.C.; Chris Pinkard, D.; Pliskin, D.P.; Podhasky, J.; Quijano, V.J.; Raczy, C.; Rae, V.H.; Rawlings, S.R.; Chiva Rodriguez, A.; Roe, P.M.; Rogers, J.; Rogert Bacigalupo, M.C.; Romanov, N.; Romieu, A.; Roth, R.K.; Rourke, N.J.; Ruediger, S.T.; Rusman, E.; Sanches-Kuiper, R.M.; Schenker, M.R.; Seoane, J.M.; Shaw, R.J.; Shiver, M.K.; Short, S.W.; Sizto, N.L.; Sluis, J.P.; Smith, M.A.; Ernest Sohna Sohna, J.; Spence, E.J.; Stevens, K.; Sutton, N.; Szajkowski, L.; Tregidgo, C.L.; Turcatti, G.; Vandevondele, S.; Verhovsky, Y.; Virk, S.M.; Wakelin, S.; Walcott, G.C.; Wang, J.; Worsley, G.J.; Yan, J.; Yau, L.; Zuerlein, M.; Rogers, J.; Mullikin, J.C.; Hurles, M.E.; McCooke, N.J.; West, J.S.; Oaks, F.L.; Lundberg, P.L.; Klenerman, D.; Durbin, R.; Smith, A.J. Accurate whole human genome sequencing using reversible terminator chemistry. Nature, 2008, 456, 53-59.
213. Ahn, S.M.; Kim, T.H.; Lee, S.; Kim, D.; Ghang, H.; Kim, D.S.; Kim, B.C.; Kim, S.Y.; Kim, W.Y.; Kim, C.; Park, D.; Lee, Y.S.; Kim, S.; Reja, R.; Jho, S.; Kim, C.G.; Cha, J.Y.; Kim, K.H.; Lee, B.; Bhak, J.; Kim, S.J. The first Korean genome sequence and analysis: full genome sequencing for a socio-ethnic group. Genome Res., 2009, 19, 1622-1629.
214. Bau, S.; Schracke, N.; Kranzle, M.; Wu, H.; Stahler, P.F.; Hoheisel, J.D.; Beier, M.; Summerer, D. Targeted next-generation sequencing by specific capture of multiple genomic loci using low-volume microfluidic DNA arrays. Anal. Bioanal. Chem., 2009, 393, 171-175.
215. Porreca, G.J.; Zhang, K.; Li, J.B.; Xie, B.; Austin, D.; Vassallo, S.L.; LeProust, E.M.; Peck, B.J.; Emig, C.J.; Dahl, F.; Gao, Y.; Church, G.M.; Shendure, J. Multiplex amplification of large sets of human exons. Nat. Methods, 2007, 4, 931-936.
216. Hodges, E.; Rooks, M.; Xuan, Z.; Bhattacharjee, A.; Benjamin Gordon, D.; Brizuela, L.; Richard McCombie, W.; Hannon, G.J. Hybrid selection of discrete genomic intervals on custom-designed microarrays for massively parallel sequencing. Nat. Protoc., 2009, 4, 960-974.
217. Hodges, E.; Xuan, Z.; Balija, V.; Kramer, M.; Molla, M.N.; Smith, S.W.; Middle, C.M.; Rodesch, M.J.; Albert, T.J.; Hannon, G.J.; McCombie, W.R. Genome-wide in situ exon capture for selective resequencing. Nat. Genet., 2007, 39, 1522-1527.
218. Via, M.; Gignoux, C.; Burchard, E.G. The 1000 Genomes Project: new opportunities for research and social challenges. Genome Med., 2010, 2, 3.
219. Siva, N. 1000 Genomes project. Nat. Biotechnol., 2008, 26, 256.
220. Kuehn, B.M. 1000 Genomes Project promises closer look at variation in human genome. JAMA, 2008, 300, 2715.
221. Vasta, V.; Ng, S.B.; Turner, E.H.; Shendure, J.; Hahn, S.H. Next generation sequence analysis for mitochondrial disorders. Genome Med., 2009, 1, 100.
222. Hedges, D.J.; Burges, D.; Powell, E.; Almonte, C.; Huang, J.; Young, S.; Boese, B.; Schmidt, M.; Pericak-Vance, M.A.; Martin, E.; Zhang, X.; Harkins, T.T.; Zuchner, S. Exome sequencing of a multigenerational human pedigree. PLoS One, 2009, 4, e8232.
223. Ng, S.B.; Buckingham, K.J.; Lee, C.; Bigham, A.W.; Tabor, H.K.; Dent, K.M.; Huff, C.D.; Shannon, P.T.; Jabs, E.W.; Nickerson, D.A.; Shendure, J.; Bamshad, M.J. Exome sequencing identifies the cause of a mendelian disorder. Nat. Genet., 2010, 42, 30-5.
224. Ng, S.B.; Turner, E.H.; Robertson, P.D.; Flygare, S.D.; Bigham, A.W.; Lee, C.; Shaffer, T.; Wong, M.; Bhattacharjee, A.; Eichler, E.E.; Bamshad, M.; Nickerson, D.A.; Shendure, J. Targeted capture and massively parallel sequencing of 12 human exomes. Nature, 2009, 461, 272-276.
225. Choi, M.; Scholl, U.I.; Ji, W.; Liu, T.; Tikhonova, I.R.; Zumbo, P.; Nayir, A.; Bakkaloglu, A.; Ozen, S.; Sanjad, S.; Nelson-Williams, C.; Farhi, A.; Mane, S.; Lifton, R.P. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc. Natl. Acad. Sci. USA, 2009, 106, 19096-19101.
226. Hoischen, A.; Gilissen, C.; Arts, P.; Wieskamp, N.; van der Vliet, W.; Vermeer, S.; Steehouwer, M.; de Vries, P.; Meijer, R.; Seiqueros, J.; Knoers, N.V.; Buckley, M.F.; Scheffer, H.; Veltman, J.A. Massively parallel sequencing of ataxia genes after array-based enrichment. Hum. Mutat., 2010, 31, 494-499.
227. Raca, G.; Jackson, C.; Warman, B.; Bair, T.; Schimmenti, L.A. Next generation sequencing in research and diagnostics of ocular birth defects. Mol. Genet. Metab., 2010, 100(2),184-192.
228. Biesecker, L.G. Exome sequencing makes medical genomics a reality. Nat. Genet., 2010, 42, 13-14.
229. Lalonde, E.; Albrecht, S.; Ha, K.C.; Jacob, K.; Bolduc, N.; Polychronakos, C.; Dechelotte, P.; Majewski, J.; Jabado, N. Unexpected allelic heterogeneity and spectrum of mutations in Fowler syndrome revealed by next-generation exome sequencing. Hum. Mutat., 2010, Epub ahead of print.
230. Gabory, A.; Ripoche, M.A.; Yoshimizu, T.; Dandolo, L. The H19 gene: regulation and function of a non-coding RNA. Cytogenet. Genome Res., 2006, 113, 188-193.
231. Brown, C.J.; Ballabio, A.; Rupert, J.L.; Lafreniere, R.G.; Grompe, M.; Tonlorenzi, R.; Willard, H.F. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature, 1991, 349, 38-44.
232. Leeb, M.; Steffen, P.A.; Wutz, A. X chromosome inactivation sparked by non-coding RNAs. RNA Biol., 2009, 6, 94-99.
233. Senner, C.E.; Brockdorff, N. Xist gene regulation at the onset of X inactivation. Curr. Opin. Genet. Dev., 2009, 19, 122-126.
234. DiMauro, S. Lessons from mitochondrial DNA mutations. Semin. Cell Dev. Biol., 2001, 12, 397-405.
235. Tuppen, H.A.; Blakely, E.L.; Turnbull, D.M.; Taylor, R.W. Mitochondrial DNA mutations and human disease. Biochim. Biophys. Acta, 2010, 1797, 113-128.
236. Manolio, T.A.; Collins, F.S.; Cox, N.J.; Goldstein, D.B.; Hindorff, L.A.; Hunter, D.J.; McCarthy, M.I.; Ramos, E.M.; Cardon, L.R.; Chakravarti, A.; Cho, J.H.; Guttmacher, A.E.; Kong, A.; Kruglyak, L.; Mardis, E.; Rotimi, C.N.; Slatkin, M.; Valle, D.; Whittemore, A.S.; Boehnke, M.; Clark, A.G.; Eichler, E.E.; Gibson, G.; Haines, J.L.; Mackay, T.F.; McCarroll, S.A.; Visscher, P.M. Finding the missing heritability of complex diseases. Nature, 2009, 461, 747-753.
237. Brinkman, R.R.; Dube, M.P.; Rouleau, G.A.; Orr, A.C.; Samuels, M.E. Human monogenic disorders - a source of novel drug targets. Nat. Rev. Genet., 2006, 7, 249-260.
238. Shimkets, R.A.; Lifton, R.P. Recent advances in the molecular genetics of hypertension. Curr. Opin. Nephrol. Hypertens., 1996, 5, 162-165.
239. Porter, J.R.; Barrett, T.G. Monogenic syndromes of abnormal glucose homeostasis: clinical review and relevance to the understanding of the pathology of insulin resistance and beta cell failure. J. Med. Genet., 2005, 42, 893-902.
240. Lifton, R.P. Genetic dissection of human blood pressure variation: common pathways from rare phenotypes. Harvey Lect., 2004, 100, 71-101.
241. Ahituv, N.; Kavaslar, N.; Schackwitz, W.; Ustaszewska, A.; Martin, J.; Hebert, S.; Doelle, H.; Ersoy, B.; Kryukov, G.; Schmidt, S.; Yosef, N.; Ruppin, E.; Sharan, R.; Vaisse, C.; Sunyaev, S.; Dent, R.; Cohen, J.; McPherson, R.; Pennacchio, L.A. Medical sequencing at the extremes of human body mass. Am. J. Hum. Genet., 2007, 80, 779-791.
242. Cohen, J.C.; Kiss, R.S.; Pertsemlidis, A.; Marcel, Y.L.; McPherson, R.; Hobbs, H.H. Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science, 2004, 305, 869-872.
243. Cohen, J.C.; Pertsemlidis, A.; Fahmi, S.; Esmail, S.; Vega, G.L.; Grundy, S.M.; Hobbs, H.H. Multiple rare variants in NPC1L1 associated with reduced sterol absorption and plasma low-density lipoprotein levels. Proc. Natl. Acad. Sci. USA, 2006, 103, 1810-1815.
244. Romeo, S.; Pennacchio, L.A.; Fu, Y.; Boerwinkle, E.; Tybjaerg-Hansen, A.; Hobbs, H.H.; Cohen, J.C. Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL. Nat. Genet., 2007, 39, 513-516.
245. Ji, W.; Foo, J.N.; O'Roak, B.J.; Zhao, H.; Larson, M.G.; Simon, D.B.; Newton-Cheh, C.; State, M.W.; Levy, D.; Lifton, R.P. Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat. Genet., 2008, 40, 592-599.
246. McCandless, S.E.; Brunger, J.W.; Cassidy, S.B. The burden of genetic disease on inpatient care in a children's hospital. Am. J. Hum. Genet., 2004, 74, 121-127.
247. Scriver, C.R.; Neal, J.L.; Saginur, R.; Clow, A. The frequency of genetic disease and congenital malformation among patients in a pediatric hospital. Can. Med. Assoc. J., 1973, 108, 1111-1115.