Genes, mutations, and human inherited disease at the dawn of the age of personalized genomics

Human Mutation

Volumn 31, Issue 6, 2010, Pages 631-655

  Cooper, David N ^a   Chen, Jian Min ^b   Ball, Edward V ^a   Howells, Katy ^a   Mort, Matthew ^a   Phillips, Andrew D ^a   Chuzhanova, Nadia ^c   Krawczak, Michael ^d   Kehrer Sawatzki, Hildegard ^e   Stenson, Peter D ^a  

^a CARDIFF UNIVERSITY   (United Kingdom)

^b INSERM   (France)

^c NOTTINGHAM TRENT UNIVERSITY   (United Kingdom)

^d UNIVERSITY OF KIEL   (Germany)

^e UNIVERSITY OF ULM   (Germany)

Author keywords

Disease genes; Functionome; Gene definition; Gene essentiality; Gene number; HGMD; Human gene mutation database; Human genome; Inherited mutations; Mutation detection; Mutome; Noncoding regions

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR 2A; MICRORNA; PIWI INTERACTING RNA; RIBOSOME RNA; SMALL INTERFERING RNA; SMALL NUCLEAR RNA; TRANSFER RNA;

3' UNTRANSLATED REGION; 5' UNTRANSLATED REGION; DNA POLYMORPHISM; GENE FUNCTION; GENE MUTATION; GENE SEQUENCE; GENE STRUCTURE; GENETIC DISORDER; GENETIC SCREENING; GENETIC VARIABILITY; GENOMICS; HUMAN; HUMAN GENOME; INTRON; NONHUMAN; NUCLEOTIDE SEQUENCE; OPEN READING FRAME; PRIORITY JOURNAL; PSEUDOGENE; REVIEW; RNA GENE; TRANSPOSON; GENETIC POLYMORPHISM; GENETIC PREDISPOSITION; GENETICS; MUTATION; PROCEDURES; REGULATORY SEQUENCE; STATISTICS AND NUMERICAL DATA; TRENDS;

GENETIC DISEASES, INBORN; GENETIC PREDISPOSITION TO DISEASE; GENOME, HUMAN; GENOMICS; HUMANS; MUTATION; OPEN READING FRAMES; POLYMORPHISM, GENETIC; REGULATORY SEQUENCES, NUCLEIC ACID;

EID: 77952733302     PISSN: 10597794     EISSN: 10981004     Source Type: Journal    
DOI: 10.1002/humu.21260     Document Type: Review

References (360)

1. Aerts S, Lambrechts D, Maity S, Van Loo P, Coessens B, De Smet F, Tranchevent LC, De Moor B, Marynen P, Hassan B, Carmeliet P, Moreau Y. 2006. Gene prioritization through genomic data fusion. Nat Biotechnol 24:537-544.
2. Akiva P, Toporik A, Edelheit S, Peretz Y, Diber A, Shemesh R, Novik A, Sorek R. 2006. Transcription-mediated gene fusion in the human genome. Genome Res 16:30-36.
3. Alkan C, Kidd JM, Marques-Bonet T, Aksay G, Antonacci F, Hormozdiari F, Kitzman JO, Baker C, Malig M, Mutlu O, Sahinalp SC, Gibbs RA, Eichler EE. 2009. Personalized copy number and segmental duplication maps using nextgeneration sequencing. Nat Genet 41:1061-1067.
4. Antonarakis SE, Cooper DN. 2007. Mutations in human genetic disease. Nature and consequences. In: Principles and practice of medical genetics. 5th ed. Rimoin DL, Connor JM, Pyeritz RE, Korf BR. edotprs. Edinburgh: Churchill Livingstone, p 101-128.
5. Arbiza L, Duchi S, Montaner D, Burguet J, Pantoja-Uceda D, Pineda-Lucena A, Dopazo J, Dopazo H. 2006. Selective pressures at a codon-level predict deleterious mutations in human disease genes. J Mol Biol 358:1390-1404.
6. Asthana S, Noble WS, Kryukov G, Grant CE, Sunyaev S, Stamatoyannopoulos JA. 2007. Widely distributed noncoding purifying selection in the human genome. Proc Natl Acad Sci USA 104:12410-12415.
7. Attanasio C, Reymond A, Humbert R, Lyle R, Kuehn MS, Neph S, Sabo PJ, Goldy J, Weaver M, Haydock A, Lee K, Dorschner M, Dermitzakis ET, Antonarakis SE, Stamatoyannopoulos JA. 2008. Assaying the regulatory potential of mammalian conserved non-coding sequences in human cells. Genome Biol 9:R168.
8. Azevedo L, Suriano G, van Asch B, Harding RM, Amorim A. 2006. Epistatic interactions: how strong in disease and evolution? Trends Genet 22:581-585.
9. Bandiera S, Hatem E, Lyonnet S, Henrion-Caude A. 2010. microRNAs in diseases: from candidate to modifier genes. Clin Genet 77:306-313.
10. Barešić A, Hopcroft LE, Rogers HH, Hurst JM, Martin AC. 2010. Compensated pathogenic deviations: analysis of structural effects. J Mol Biol 396:19-30.
11. Barral DC, Ramalho JS, Anders R, Hume AN, Knapton HJ, Tolmachova T, Collinson LM, Goulding D, Authi KS, Seabra MC. 2002. Functional redundancy of Rab27 proteins and the pathogenesis of Griscelli syndrome. J Clin Invest 110:247-257.
12. Bastepe M, Fröhlich LF, Linglart A, Abu-Zahra HS, Tojo K, Ward LM, Jüppner H. 2005. Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib. Nat Genet 37:25-27.
13. Beckmann JS, Sharp AJ, Antonarakis SE. 2008. CNVs and genetic medicine (excitement and consequences of a rediscovery). Cytogenet Genome Res 123:7-16.
14. Benito-Sanz S, Thomas NS, Huber C, Gorbenko del Blanco D, Aza-Carmona M, Crolla JA, Maloney V, Rappold G, Argente J, Campos-Barros A, Cormier-Daire V, Heath KE. 2005. A novel class of pseudoautosomal region 1 deletions downstream of SHOX is associated with Leri-Weill dyschondrosteosis. Am J Hum Genet 77:533-544.
15. Benko S, Fantes JA, Amiel J, Kleinjan DJ, Thomas S, Ramsay J, Jamshidi N, Essafi A, Heaney S, Gordon CT, McBride D, Golzio C, Fisher M, Perry P, Abadie V, Ayuso C, Holder-Espinasse M, Kilpatrick N, Lees MM, Picard A, Temple IK, Thomas P, Vazquez MP, Vekemans M, Crollius HR, Hastie ND, Munnich A, Etchevers HC, Pelet A, Farlie PG, Fitzpatrick DR, Lyonnet S. 2009. Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence. Nat Genet 41:359-364.
16. Bird CP, Stranger BE, Liu M, Thomas DJ, Ingle CE, Beazley C, Miller W, Hurles ME, Dermitzakis ET. 2007. Fast-evolving noncoding sequences in the human genome. Genome Biol 8:R118.
17. Bittles AH, Neel JV. 1994. The costs of human inbreeding and their implications for variations at the DNA level. Nat Genet 8:117-121.
18. Bochukova EG, Huang N, Keogh J, Henning E, Purmann C, Blaszczyk K, Saeed S, Hamilton-Shield J, Clayton-Smith J, O'Rahilly S, Hurles ME, Farooqi IS. 2010. Large, rare chromosomal deletions associated with severe early-onset obesity. Nature 463:666-670.
19. Borel C, Antonarakis SE. 2008. Functional genetic variation of human miRNAs and phenotypic consequences. Mamm Genome 19:503-509.
20. Borel C, Gagnebin M, Gehrig C, Kriventseva EV, Zdobnov EM, Antonarakis SE. 2008. Mapping of small RNAs in the human ENCODE regions. Am J Hum Genet 82:971-981.
21. Boyko AR, Williamson SH, Indap AR, Degenhardt JD, Hernandez RD, Lohmueller KE, Adams MD, Schmidt S, Sninsky JJ, Sunyaev SR, White TJ, Nielsen R, Clark AG, Bustamante CD. 2008. Assessing the evolutionary impact of amino acid mutations in the human genome. PLoS Genet 4:e1000083.
22. Brakenhoff RH, Henskens HA, van Rossum MW, Lubsen NH, Schoenmakers JG. 1994. Activation of the gamma E-crystallin pseudogene in the human hereditary Coppock-like cataract. Hum Mol Genet 3:279-283. (Pubitemid 2047237)
23. Brouwer JR, Willemsen R, Oostra BA. 2009. Microsatellite repeat instability and neurological disease. Bioessays 31:71-83.
24. Brown KK, Reiss JA, Crow K, Ferguson HL, Kelly C, Fritzsch B, Morton CC. 2010. Deletion of an enhancer near DLX5 and DLX6 in a family with hearing loss, craniofacial defects, and an inv(7)(q21.3q35). Hum Genet 127:19-31.
25. Buschiazzo E, Gemmell NJ. 2010. Conservation of human microsatellites across 450 million years of evolution. Genome Biol Evol 2010:153-165.
26. Cai J, Goodman BK, Patel AS, Mulliken JB, Van Maldergem L, Hoganson GE, Paznekas WA, Ben-Neriah Z, Sheffer R, Cunningham ML, Daentl DL, Jabs EW. 2003. Increased risk for developmental delay in Saethre-Chotzen syndrome is associated with TWIST deletions: an improved strategy for TWIST mutation screening. Hum Genet 114:68-76.
27. Cai JJ, Borenstein E, Chen R, Petrov DA. 2009. Similarly strong purifying selection acts on human disease genes of all evolutionary ages. Genome Biol Evol 2009:131-144.
28. Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. 2005. A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 353:1793-1801.
29. Calvo SE, Pagliarini DJ, Mootha VK. 2009. Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans. Proc Natl Acad Sci USA 106:7507-7512.
30. Capriotti E, Arbiza L, Casadio R, Dopazo J, Dopazo H, Marti-Renom MA. 2008. Use of estimated evolutionary strength at the codon level improves the prediction of disease-related protein mutations in humans. Hum Mutat 29:198-204.
31. Carninci P, Sandelin A, Lenhard B, Katayama S, Shimokawa K, Ponjavic J, Semple CA, Taylor MS, Engström PG, Frith MC, Forrest AR, Alkema WB, Tan SL, Plessy C, Kodzius R, Ravasi T, Kasukawa T, Fukuda S, Kanamori-Katayama M, Kitazume Y, Kawaji H, Kai C, Nakamura M, Konno H, Nakano K, Mottagui-Tabar S, Arner P, Chesi A, Gustincich S, Persichetti F, Suzuki H, Grimmond SM, Wells CA, Orlando V, Wahlestedt C, Liu ET, Harbers M, Kawai J, Bajic VB, Hume DA, Hayashizaki Y. 2006. Genome-wide analysis of mammalian promoter architecture and evolution. Nat Genet 38:626-635.
32. Cartegni L, Chew SL, Krainer AR. 2002. Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat Rev Genet 3:285-298. (Pubitemid 34279797)
33. Cecchini KR, Raja Banerjee A, Kim TH. 2009. Towards a genome-wide reconstruction of cis-regulatory networks in the human genome. Semin Cell Dev Biol 20:842-848.
34. Chang JC, Kan YW. 1979. b0 thalassemia, a nonsense mutation in man. Proc Natl Acad Sci USA 76:2886-2889.
35. Chatterjee S, Pal JK. 2009. Role of 5′- and 3′-untranslated regions of mRNAs in human diseases. Biol Cell 101:251-262.
36. Chen CT, Wang JC, Cohen BA. 2007. The strength of selection on ultraconserved elements in the human genome. Am J Hum Genet 80:692-704. (Pubitemid 46564406)
37. Chen J, Wildhardt G, Zhong Z, Röth R, Weiss B, Steinberger D, Decker J, Blum WF, Rappold G. 2009a. Enhancer deletions of the SHOX gene as a frequent cause of short stature: the essential role of a 250 kb downstream regulatory domain. J Med Genet 46:834-839.
38. Chen JM, Férec C, Cooper DN. 2006a. A systematic analysis of disease-associated variants in the 3′ regulatory regions of human protein-coding genes I: general principles and overview. Hum Genet 120:1-21.
39. Chen JM, Férec C, Cooper DN. 2006b. A systematic analysis of disease-associated variants in the 3′ regulatory regions of human protein-coding genes II: the importance of mRNA secondary structure in assessing the functionality of 3′ UTR variants. Hum Genet 120:301-333.
40. Chen JM, Férec C, Cooper DN. 2009b. Closely spaced multiple mutations as potential signatures of transient hypermutability in human genes. Hum Mutat 30:1435-1448.
41. Choi JW, Park CS, Hwang M, Nam HY, Chang HS, Park SG, Han BG, Kimm K, Kim HL, Oh B, Kim Y. 2008. A common intronic variant of CXCR3 is functionally associated with gene expression levels and the polymorphic immune cell responses to stimuli. J Allergy Clin Immunol 122: 1119-1126.e7.
42. 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. 2009. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci USA 106:19096-19101.
43. Chorley BN, Wang X, Campbell MR, Pittman GS, Noureddine MA, Bell DA. 2008. Discovery and verification of functional single nucleotide polymorphisms in regulatory genomic regions: current and developing technologies. Mutat Res 659:147-157.
44. Chun S, Fay JC. 2009. Identification of deleterious mutations within three human genomes. Genome Res 19:1553-1561.
45. Clamp M, Fry B, Kamal M, Xie X, Cuff J, Lin MF, Kellis M, Lindblad-Toh K, Lander ES. 2010. Distinguishing protein-coding and noncoding genes in the human genome. Proc Natl Acad Sci USA 104:19428-19433.
46. Collins LJ, Penny D. 2009. The RNA infrastructure: dark matter of the eukaryotic cell? Trends Genet 25:120-128.
47. Conley AB, Miller WJ, Jordan IK. 2008. Human cis natural antisense transcripts initiated by transposable elements. Trends Genet 24:53-56.
48. Conrad DF, Pinto D, Redon R, Feuk L, Gokcumen O, Zhang Y, Aerts J, Andrews TD, Barnes C, Campbell P, Fitzgerald T, Hu M, Ihm CH, Kristiansson K, Macarthur DG, Macdonald JR, Onyiah I, Pang AW, Robson S, Stirrups K, Valsesia A, Walter K, Wei J, The Wellcome Trust Case Control Consortium, Tyler-Smith C, Carter NP, Lee C, Scherer SW, Hurles ME. 2010. Origins and functional impact of copy number variation in the human genome. Nature 464:704-712.
49. Cotton RGH. 2009. Collection of variation causing disease-the Human Variome Project. Hum Genomics 3:301-303.
50. Coulombe-Huntington J, Lam KC, Dias C, Majewski J. 2009. Fine-scale variation and genetic determinants of alternative splicing across individuals. PLoS Genet 5:e1000766.
51. Coutinho AM, Oliveira G, Katz C, Feng J, Yan J, Yang C, Marques C, Ataíde A, Miguel TS, Borges L, Almeida J, Correia C, Currais A, Bento C, Mota-Vieira L, Temudo T, Santos M, Maciel P, Sommer SS, Vicente AM. 2007. MECP2 coding sequence and 3′UTR variation in 172 unrelated autistic patients. Am J Med Genet B Neuropsychiatr Genet 144B:475-483.
52. Coutinho G, Xie J, Du L, Brusco A, Krainer AR, Gatti RA. 2005. Functional significance of a deep intronic mutation in the ATM gene and evidence for an alternative exon 28a. Hum Mutat 25:118-124.
53. Cropley JE, Martin DI, Suter CM. 2008. Germline epimutation in humans. Pharmacogenomics 9:1861-1868.
54. Cutler G, Kassner PD. 2008. Copy number variation in the mouse genome: implications for the mouse as a model organism for human disease. Cytogenet Genome Res 123:297-306.
55. Dathe K, Kjaer KW, Brehm A, Meinecke P, Nürnberg P, Neto JC, Brunoni D, Tommerup N, Ott CE, Klopocki E, Seemann P, Mundlos S. 2009. Duplications involving a conserved regulatory element downstream of BMP2 are associated with brachydactyly type A2. Am J Hum Genet 84:483-492.
56. Dear A, Daly J, Brennan SO, Tuckfield A, George PM. 2006. An intronic mutation within FGB (IVS1+2076 a→g) is associated with afibrinogenemia and recurrent transient ischemic attacks. J Thromb Haemost 4:471-472.
57. Dear PH. 2009. Copy-number variation: the end of the human genome? Trends Biotechnol 27:448-454.
58. De Gobbi M, Viprakasit V, Hughes JR, Fisher C, Buckle VJ, Ayyub H, Gibbons RJ, Vernimmen D, Yoshinaga Y, de Jong P, Cheng JF, Rubin EM, Wood WG, Bowden D, Higgs DR. 2006. A regulatory SNP causes a human genetic disease by creating a new transcriptional promoter. Science 312:1215-1217.
59. de Kok YJ, Vossenaar ER, Cremers CW, Dahl N, Laporte J, Hu LJ, Lacombe D, Fischel-Ghodsian N, Friedman RA, Parnes LS, Thorpe P, Bitner-Glindzicz M, Pander HJ, Heilbronner H, Graveline J, den Dunnen JT, Brunner HG, Ropers HH, Cremers FP. 1996. Identification of a hot spot for microdeletions in patients with X-linked deafness type 3 (DFN3) 900 kb proximal to the DFN3 gene POU3F4. Hum Mol Genet 5:1229-1235.
60. de Smith AJ, Walters RG, Froguel P, Blakemore AI. 2008. Human genes involved in copy number variation: mechanisms of origin, functional effects and implications for disease. Cytogenet Genome Res 123:17-26.
61. Dehainault C, Michaux D, Pagès-Berhouet S, Caux-Moncoutier V, Doz F, Desjardins L, Couturier J, Parent P, Stoppa-Lyonnet D, Gauthier-Villars M, Houdayer C. 2007. A deep intronic mutation in the RB1 gene leads to intronic sequence exonisation. Eur J Hum Genet 15:473-477.
62. Denoeud F, Kapranov P, Ucla C, Frankish A, Castelo R, Drenkow J, Lagarde J, Alioto T, Manzano C, Chrast J, Dike S, Wyss C, Henrichsen CN, Holroyd N, Dickson MC, Taylor R, Hance Z, Foissac S, Myers RM, Rogers J, Hubbard T, Harrow J, Guigó R, Gingeras TR, Antonarakis SE, Reymond A. 2007. Prominent use of distal 5′ transcription start sites and discovery of a large number of additional exons in ENCODE regions. Genome Res 17:746-759.
63. D'haene B, Attanasio C, Beysen D, Dostie J, Lemire E, Bouchard P, Field M, Jones K, Lorenz B, Menten B, Buysse K, Pattyn F, Friedli M, Ucla C, Rossier C, Wyss C, Speleman F, De Paepe A, Dekker J, Antonarakis SE, De Baere E. 2009. Disease-causing 7.4 kb cis-regulatory deletion disrupting conserved non-coding sequences and their interaction with the FOXL2 promotor: implications for mutation screening. PLoS Genet 5:e1000522.
64. Dhir A, Buratti E. 2010. Alternative splicing: role of pseudoexons in human disease and potential therapeutic strategies. FEBS J 277:841-855.
65. Di Rienzo A, Hudson RR. 2005. An evolutionary framework for common diseases: the ancestral-susceptibility model. Trends Genet 21:596-601.
66. Dickson SP, Wang K, Krantz I, Hakonarson H, Goldstein DB. 2010. Rare variants create synthetic genome-wide associations. PLoS Biol 8:e1000294.
67. Dimas AS, Deutsch S, Stranger BE, Montgomery SB, Borel C, Attar-Cohen H, Ingle C, Beazley C, Gutierrez Arcelus M, Sekowska M, Gagnebin M, Nisbett J, Deloukas P, Dermitzakis ET, Antonarakis SE. 2009. Common regulatory variation impacts gene expression in a cell type-dependent manner. Science 325:1246-1250.
68. Dimas AS, Stranger BE, Beazley C, Finn RD, Ingle CE, Forrest MS, Ritchie ME, Deloukas P, Tavaré S, Dermitzakis ET. 2008. Modifier effects between regulatory and protein-coding variation. PLoS Genet 4:e1000244.
69. Dinger ME, Amaral PP, Mercer TR, Mattick JS. 2009. Pervasive transcription of the eukaryotic genome: functional indices and conceptual implications. Brief Funct Genomic Proteomic 8:407-423.
70. Dixit M, Ansseau E, Tassin A, Winokur S, Shi R, Qian H, Sauvage S, Mattéotti C, van Acker AM, Leo O, Figlewicz D, Barro M, Laoudj-Chenivesse D, Belayew A, Coppée F, Chen YW. 2007. DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1. Proc Natl Acad Sci USA 104:18157-18162.
71. Domazet-Lošo T, Tautz D. 2008. An ancient evolutionary origin of genes associated with human genetic diseases. Mol Biol Evol 25:2699-2707.
72. Dong XY, Rodriguez C, Guo P, Sun X, Talbot JT, Zhou W, Petros J, Li Q, Vessella RL, Kibel AS, Stevens VL, Calle EE, Dong JT. 2008. SnoRNA U50 is a candidate tumor-suppressor gene at 6q14.3 with a mutation associated with clinically significant prostate cancer. Hum Mol Genet 17:1031-1042.
73. Drake JA, Bird C, Nemesh J, Thomas DJ, Newton-Cheh C, Reymond A, Excoffier L, Attar H, Antonarakis SE, Dermitzakis ET, Hirschhorn JN. 2006. Conserved noncoding sequences are selectively constrained and not mutation cold spots. Nat Genet 38:223-227.
74. Driscoll MC, Dobkin CS, Alter BP. 1989. gdb-thalassemia due to a de novo mutation deleting the 5′ β-globin gene activation-region hypersensitive sites. Proc Natl Acad Sci USA 86:7470-7474.
75. Elia J, Gai X, Xie HM, Perin JC, Geiger E, Glessner JT, D'arcy M, Deberardinis R, Frackelton E, Kim C, Lantieri F, Muganga BM, Wang L, Takeda T, Rappaport EF, Grant SF, Berrettini W, Devoto M, Shaikh TH, Hakonarson H, White PS. 2009. Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes. Mol Psychiatry (in press).
76. Emison ES, McCallion AS, Kashuk CS, Bush RT, Grice E, Lin S, Portnoy ME, Cutler DJ, Green ED, Chakravarti A. 2005. A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk. Nature 434:857-863.
77. Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Järvelä I. 2002. Identification of a variant associated with adult-type hypolactasia. Nat Genet 30:233-237.
78. ENCODE Project Consortium, 2007. 2007. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799-816.
79. Eory L, Halligan DL, Keightley PD. 2010. Distributions of selectively constrained sites and deleterious mutation rates in the hominid and murid genomes. Mol Biol Evol 27:177-192.
80. Faghihi MA, Wahlestedt C. 2009. Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol 10:637-643.
81. Fanciulli M, Petretto E, Aitman TJ. 2010. Gene copy number variation and common human disease. Clin Genet 77:201-213.
82. Fantauzzo KA, Tadin-Strapps M, You Y, Mentzer SE, Baumeister FA, Cianfarani S, Van Maldergem L, Warburton D, Sundberg JP, Christiano AM. 2008. A position effect on TRPS1 is associated with Ambras syndrome in humans and the Koala phenotype in mice. Hum Mol Genet 17:3539-3551.
83. Fay JC, Wyckoff GJ, Wu CI. 2001. Positive and negative selection on the human genome. Genetics 158:1227-1234. (Pubitemid 32667107)
84. Fejes-Toth K, Sotirova V, Sachidanandam R, Assaf G, Hannon GJ, Kapranov P, Foissac S, Willingham AT, Duttagupta R, Dumais E, Gingeras TR. 2009. Post-transcriptional processing generates a diversity of 5′-modified long and short RNAs. Nature 457:1028-1032.
85. Feldman I, Rzhetsky A, Vitkup D. 2008. Network properties of genes harboring inherited disease mutations. Proc Natl Acad Sci USA 105:4323-4328.
86. Ferrer-Costa C, Orozco M, de la Cruz X. 2002. Characterization of disease-associated single amino acid polymorphisms in terms of sequence and structure properties. J Mol Biol 315:771-786.
87. Ferrer-Costa C, Orozco M, de la Cruz X. 2007. Characterization of compensated mutations in terms of structural and physico-chemical properties. J Mol Biol 365:249-256.
88. Flomen RH, Vatcheva R, Gorman PA, Baptista PR, Groet J, Barisić I, Ligutic I, Nizetić D. 1998. Construction and analysis of a sequence-ready map in 4q25: Rieger syndrome can be caused by haploinsufficiency of RIEG, but also by chromosome breaks approximately 90 kb upstream of this gene. Genomics 47:409-413. (Pubitemid 28110655)
89. Fraser HB, Xie X. 2009. Common polymorphic transcript variation in human disease. Genome Res 19:567-575.
90. Frazer KA, Murray SS, Schork NJ, Topol EJ. 2009. Human genetic variation and its contribution to complex traits. Nat Rev Genet 10:241-251.
91. Furney SJ, Albà MM, López-Bigas N. 2006. Differences in the evolutionary history of disease genes affected by dominant or recessive mutations. BMC Genomics 7:165.
92. Furniss D, Lettice LA, Taylor IB, Critchley PS, Giele H, Hill RE, Wilkie AO. 2008. A variant in the sonic hedgehog regulatory sequence (ZRS) is associated with triphalangeal thumb and deregulates expression in the developing limb. Hum Mol Genet 17:2417-2423.
93. Gale JS. 1990. Theoretical population genetics. London: Unwin Hyman, p 325-343.
94. Gao L, Zhang J. 2003. Why are some human disease-associated mutations fixed in mice? Trends Genet 19:678-681.
95. Gerdes S, Edwards R, Kubal M, Fonstein M, Stevens R, Osterman A. 2006. Essential genes on metabolic maps. Curr Opin Biotechnol 17:448-456.
96. Gerstein MB, Bruce C, Rozowsky JS, Zheng D, Du J, Korbel JO, Emanuelsson O, Zhang ZD, Weissman S, Snyder M. 2007. What is a gene, post-ENCODE? History and updated definition. Genome Res 17:669-681.
97. Gibbs RA, Rogers J, KatzeMG, Bumgarner R,Weinstock GM,Mardis ER, Remington KA, Strausberg RL, Venter JC, Wilson RK, Batzer MA, Bustamante CD, Eichler EE, Hahn MW, Hardison RC, Makova KD, Miller W, Milosavljevic A, Palermo RE, Siepel A, Sikela JM, Attaway T, Bell S, Bernard KE, Buhay CJ, Chandrabose MN, Dao M, Davis C, Delehaunty KD, Ding Y, Dinh HH, Dugan-Rocha S, Fulton LA, Gabisi RA, Garner TT, Godfrey J, Hawes AC, Hernandez J, Hines S, Holder M, Hume J, Jhangiani SN, Joshi V, Khan ZM, Kirkness EF, Cree A, Fowler RG, Lee S, Lewis LR, Li Z, Liu YS, Moore SM, Muzny D, Nazareth LV, Ngo DN, Okwuonu GO, Pai G, Parker D, Paul HA, Pfannkoch C, Pohl CS, Rogers YH, Ruiz SJ, Sabo A, Santibanez J, Schneider BW, Smith SM, Sodergren E, Svatek AF, Utterback TR, Vattathil S, Warren W, White CS, Chinwalla AT, Feng Y, Halpern AL, Hillier LW, Huang X, Minx P, Nelson JO, Pepin KH, Qin X, Sutton GG, Venter E, Walenz BP, Wallis JW, Worley KC, Yang SP, Jones SM, Marra MA, Rocchi M, Schein JE, Baertsch R, Clarke L, Csürös M, Glasscock J, Harris RA, Havlak P, Jackson AR, Jiang H, Liu Y,Messina DN, Shen Y, Song HX, Wylie T, Zhang L, Birney E, Han K, Konkel MK, Lee J, Smit AF, Ullmer B, Wang H, Xing J, Burhans R, Cheng Z, Karro JE,Ma J, Raney B, She X, Cox MJ,Demuth JP,Dumas LJ, Han SG, Hopkins J, Karimpour-Fard A, Kim YH, Pollack JR, Vinar T, Addo-Quaye C, Degenhardt J, Denby A, Hubisz MJ, Indap A, Kosiol C, Lahn BT, Lawson HA, Marklein A, Nielsen R, Vallender EJ, Clark AG, Ferguson B, Hernandez RD, Hirani K, Kehrer-Sawatzki H, Kolb J, Patil S, Pu LL, Ren Y, Smith DG,Wheeler DA, Schenck I, Ball EV, Chen R, Cooper DN, Giardine B, Hsu F, Kent WJ, Lesk A, Nelson DL, O'Brien WE, Prüfer K, Stenson PD, Wallace JC, Ke H, Liu XM, Wang P, Xiang AP, Yang F, Barber GP, Haussler D, Karolchik D, Kern AD, Kuhn RM, Smith KE, Zwieg AS. 2007. Evolutionary and biomedical insights from the rhesus macaque genome. Science 316:222-234. (Pubitemid 46633091)
98. Gingeras TR. 2007. Origin of phenotypes: genes and transcripts. Genome Res 17:682-690.
99. Gingeras TR. 2009. Implications of chimaeric non-co-linear transcripts. Nature 461:206-211.
100. Girirajan S, Rosenfeld JA, Cooper GM, Antonacci F, Siswara P, Itsara A, Vives L, Walsh T, McCarthy SE, Baker C, Mefford HC, Kidd JM, Browning SR, Browning BL, Dickel DE, Levy DL, Ballif BC, Platky K, Farber DM, Gowans GC, Wetherbee JJ, Asamoah A, Weaver DD, Mark PR, Dickerson J, Garg BP, Ellingwood SA, Smith R, Banks VC, Smith W, McDonald MT, Hoo JJ, French BN, Hudson C, Johnson JP, Ozmore JR, Moeschler JB, Surti U, Escobar LF, El-Khechen D, Gorski JL, Kussmann J, Salbert B, Lacassie Y, Biser A, McDonald-McGinn DM, Zackai EH, Deardorff MA, Shaikh TH, Haan E, Friend KL, Fichera M, Romano C, Gécz J, DeLisi LE, Sebat J, King MC, Shaffer LG, Eichler EE. 2010. A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nat Genet 2010 42:203-209.
101. Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, Wood S, Zhang H, Estes A, Brune CW, Bradfield JP, Imielinski M, Frackelton EC, Reichert J, Crawford EL, Munson J, Sleiman PM, Chiavacci R, Annaiah K, Thomas K, Hou C, Glaberson W, Flory J, Otieno F, Garris M, Soorya L, Klei L, Piven J, Meyer KJ, Anagnostou E, Sakurai T, Game RM, Rudd DS, Zurawiecki D, McDougle CJ, Davis LK, Miller J, Posey DJ, Michaels S, Kolevzon A, Silverman JM, Bernier R, Levy SE, Schultz RT, Dawson G, Owley T, McMahon WM, Wassink TH, Sweeney JA, Nurnberger JI, Coon H, Sutcliffe JS, Minshew NJ, Grant SF, Bucan M, Cook EH, Buxbaum JD, Devlin B, Schellenberg GD, Hakonarson H. 2009. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 459:569-573.
102. Glinskii AB, Ma J, Ma S, Grant D, Lim CU, Sell S, Glinsky GV. 2009. Identification of intergenic trans-regulatory RNAs containing a disease-linked SNP sequence and targeting cell cycle progression/differentiation pathways in multiple common human disorders. Cell Cycle 8:3925-3942.
103. Goh KI, Cusick ME, Valle D, Childs B, Vidal M, Barabási AL. 2007. The human disease network. Proc Natl Acad Sci USA 104:8685-8690.
104. Goode DL, Cooper GM, Schmutz J, Dickson M, Gonzales E, Tsai M, Karra K, Davydov E, Batzoglou S, Myers RM, Sidow A. 2010. Evolutionary constraint facilitates interpretation of genetic variation in resequenced human genomes. Genome Res 20:301-310.
105. Gordon CT, Tan TY, Benko S, Fitzpatrick D, Lyonnet S, Farlie PG. 2009. Long-range regulation at the SOX9 locus in development and disease. J Med Genet 46:649-656.
106. Gorlov IP, Kimmel M, Amos CI. 2006. Strength of the purifying selection against different categories of the point mutations in the coding regions of the human genome. Hum Mol Genet 15:1143-1150.
107. Gorlov IP, Gorlova OY, Amos CI. 2008. Relative effects of mutability and selection on single nucleotide polymorphisms in transcribed regions of the human genome. BMC Genomics 9:292.
108. Grant SF, Reid DM, Blake G, Herd R, Fogelman I, Ralston SH. 1996. Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene. Nat Genet 14:203-205.
109. Griffiths-Jones S. 2007. Annotating noncoding RNA genes. Annu Rev Genomics Hum Genet 8:279-298.
110. Grinchuk OV, Jenjaroenpun P, Orlov YL, Zhou J, Kuznetsov VA. 2010. Integrative analysis of the human cis-antisense gene pairs, miRNAs and their transcription regulation patterns. Nucleic Acids Res 38:534-547.
111. Gross-Hardt S, Reiss J. 2002. The bicistronic MOCS1 gene has alternative start codons on two mutually exclusive exons. Mol Genet Metab 76:340-343.
112. Gurnett CA, Bowcock AM, Dietz FR, Morcuende JA, Murray JC, Dobbs MB. 2007. Two novel point mutations in the long-range SHH enhancer in three families with triphalangeal thumb and preaxial polydactyly. Am J Med Genet A 143:27-32.
113. Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES. 2009. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458:223-227.
114. Haiman CA, Le Marchand L, Yamamato J, Stram DO, Sheng X, Kolonel LN, Wu AH, Reich D, Henderson BE. 2007. A common genetic risk factor for colorectal and prostate cancer. Nat Genet 39:954-956.
115. Harland M, Mistry S, Bishop DT, Bishop JA. 2001. A deep intronic mutation in CDKN2A is associated with disease in a subset of melanoma pedigrees. Hum Mol Genet 10:2679-2686. (Pubitemid 33133409)
116. Harrison PM, Zheng D, Zhang Z, Carriero N, Gerstein M. 2005. Transcribed processed pseudogenes in the human genome: an intermediate form of expressed retrosequence lacking protein-coding ability. Nucleic Acids Res 33:2374-2383.
117. Harteveld CL, Voskamp A, Phylipsen M, Akkermans N, den Dunnen JT, White SJ, Giordano PC. 2005. Nine unknown rearrangements in 16p13.3 and 11p15.4 causingα- and β-thalassaemia characterised by high resolution multiplex ligation-dependent probe amplification. J Med Genet 42:922-931.
118. Hatton CS, Wilkie AO, Drysdale HC, Wood WG, Vickers MA, Sharpe J, Ayyub H, Pretorius IM, Buckle VJ, Higgs DR. 1990.α-Thalassemia caused by a large (62 kb) deletion upstream of the human α-globin gene cluster. Blood 76:221-227. (Pubitemid 20220814)
119. He Y, Vogelstein B, Velculescu VE, Papadopoulos N, Kinzler KW. 2008. The antisense transcriptomes of human cells. Science 322:1855-1857.
120. Hedges DJ, Burges D, Powell E, Almonte C, Huang J, Young S, Boese B, Schmidt M, Pericak-Vance MA, Martin E, Zhang X, Harkins TT, Züchner S. 2009. Exome sequencing of a multigenerational human pedigree. PLoS One 4:e8232.
121. Heintzman ND, Ren B. 2009. Finding distal regulatory elements in the human genome. Curr Opin Genet Dev 19:541-549.
122. Herzog H, Darby K, Hort YJ, Shine J. 1996. Intron 17 of the human retinoblastoma susceptibility gene encodes an actively transcribed G protein-coupled receptor gene. Genome Res 6:858-861. (Pubitemid 26385366)
123. Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, Manolio TA. 2009. Potential etiologic and functional implications of genomewide association loci for human diseases and traits. Proc Natl Acad Sci USA 106:9362-9367.
124. Hirotsune S, Yoshida N, Chen A, Garrett L, Sugiyama F, Takahashi S, Yagami K, Wynshaw-Boris A, Yoshiki A. 2003. An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene. Nature 423:91-96.
125. Hitchins MP, Ward RL. 2009. Constitutional (germline) MLH1 epimutation as an aetiological mechanism for hereditary non-polyposis colorectal cancer. J Med Genet 46:793-802.
126. Homolova K, Zavadakova P, Doktor TK, Schroeder LD, Kozich V, Andresen BS. 2010. The deep intronic c.903+469T>C mutation in the MTRR gene creates an SF2/ ASF binding exonic splicing enhancer, which leads to pseudoexon activation and causes the cblE type of homocystinuria. Hum Mutat 31:437-444.
127. Howard OM, Turpin JA, Goldman R, Modi WS. 2004. Functional redundancy of the human CCL4 and CCL4L1 chemokine genes. Biochem Biophys Res Commun 320:927-931.
128. Hsiao T-L, Vitkup D. 2008. Role of duplicate genes in robustness against deleterious human mutations. PLoS Genet 4:e1000014.
129. Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L, Zeng Y, Miao R, Jin G, Ma H, Chen Y, Shen H. 2008. Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest 118:2600-2608.
130. Hu Z, Liang J, Wang Z, Tian T, Zhou X, Chen J, Miao R, Wang Y, Wang X, Shen H. 2009. Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women. Hum Mutat 30:79-84.
131. Huang H, Winter EE, Wang H, Weinstock KG, Xing H, Goodstadt L, Stenson PD, Cooper DN, Smith D, Albà MM, Ponting CP, Fechtel K. 2004. Evolutionary conservation and selection of human disease gene orthologs in the rat and mouse genomes. Genome Biol 5:R47.
132. Hunt R, Sauna ZE, Ambudkar SV, Gottesman MM, Kimchi-Sarfaty C. 2009. Silent (synonymous) SNPs: should we care about them? Methods Mol Biol 578:23-39.
133. Iafrate AJ, Feuk L, Rivera MN, Listewnik ML, Donahoe PK, Qi Y, Scherer SW, Lee C. 2004. Detection of large-scale variation in the human genome. Nat Genet 36:949-951.
134. International Human Genome Sequencing Consortium. 2004. Finishing the euchromatic sequence of the human genome. Nature 431:931-945.
135. Jarinova O, Stewart AF, Roberts R, Wells G, Lau P, Naing T, Buerki C, McLean BW, Cook RC, Parker JS, McPherson R. 2009. Functional analysis of the chromosome 9p21.3 coronary artery disease risk locus. Arterioscler Thromb Vasc Biol 29:1671-1677.
136. Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la
137. Jimenez-Sanchez G, Childs B, Valle D. 2001. Human disease genes. Nature 409:853-855.
138. Jones S, Hruban RH, Kamiyama M, Borges M, Zhang X, Parsons DW, Lin JC, Palmisano E, Brune K, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Parmigiani G, Kern SE, Velculescu VE, Kinzler KW, Vogelstein B, Eshleman JR, Goggins M, Klein AP. 2009. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 324:217.
139. Jordan IK, Rogozin IB, Glazko GV, Koonin EV. 2003. Origin of a substantial fraction of human regulatory sequences from transposable elements. Trends Genet 19:68-72.
140. Kapranov P, Cawley SE, Drenkow J, Bekiranov S, Strausberg RL, Fodor SP, Gingeras TR. 2002. Large-scale transcriptional activity in chromosomes 21 and 22. Science 296:916-919.
141. Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermüller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR. 2007b. RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316:1484-1488.
142. Kapranov P, Drenkow J, Cheng J, Long J, Helt G, Dike S, Gingeras TR. 2005. Examples of the complex architecture of the human transcriptome revealed by RACE and high-density tiling arrays. Genome Res 15:987-997.
143. Kapranov P, Willingham AT, Gingeras TR. 2007a. Genome-wide transcription and the implications for genomic organization. Nat Rev Genet 8:413-423.
144. Karchin R. 2009. Next generation tools for the annotation of human SNPs. Brief Bioinform 10:35-52.
145. Kasowski M, Grubert F, Heffelfinger C, Hariharan M, Asabere A, Waszak SM, Habegger L, Rozowsky J, Shi M, Urban AE, Hong MY, Karczewski KJ, Huber W, Weissman SM, Gerstein MB, Korbel JO, Snyder M. 2010. Variation in transcription factor binding among humans. Science 328:232-235.
146. Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M, Nishida H, Yap CC, Suzuki M, Kawai J, Suzuki H, Carninci P, Hayashizaki Y, Wells C, Frith M, Ravasi T, Pang KC, Hallinan J, Mattick J, Hume DA, Lipovich L, Batalov S, Engström PG, Mizuno Y, Faghihi MA, Sandelin A, Chalk AM, Mottagui-Tabar S, Liang Z, Lenhard B, Wahlestedt C, RIKEN Genome Exploration Research Group, Genome Science Group (Genome Network Project Core Group), FANTOM Consortium. 2005. Antisense transcription in the mammalian transcriptome. Science 309:1564-1566.
147. Katzman S, Kern AD, Bejerano G, Fewell G, Fulton L, Wilson RK, Salama SR, Haussler D. 2007. Human genome ultraconserved elements are ultraselected. Science 317:915.
148. Kawaji H, Hayashizaki Y. 2008. Exploration of small RNAs. PLoS Genet 4:e22.
149. Keightley PD, Kryukov GV, Sunyaev S, Halligan DL, Gaffney DJ. 2005. Evolutionary constraints in conserved nongenic sequences of mammals. Genome Res 15:1373-1378.
150. Khachane AN, Harrison PM. 2009. Assessing the genomic evidence for conserved transcribed pseudogenes under selection. BMC Genomics 10:435.
151. Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, Regev A, Lander ES, Rinn JL. 2009. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci USA 106:11667-11672.
152. Kidd JM, Cooper GM, Donahue WF, Hayden HS, Sampas N, Graves T, Hansen N, Teague B, Alkan C, Antonacci F, Haugen E, Zerr T, Yamada NA, Tsang P, Newman TL, Tüzün E, Cheng Z, Ebling HM, Tusneem N, David R, Gillett W, Phelps KA, Weaver M, Saranga D, Brand A, Tao W, Gustafson E, McKernan K, Chen L, Malig M, Smith JD, Korn JM, McCarroll SA, Altshuler DA, Peiffer DA, Dorschner M, Stamatoyannopoulos J, Schwartz D, Nickerson DA, Mullikin JC, Wilson RK, Bruhn L, Olson MV, Kaul R, Smith DR, Eichler EE. 2008. Mapping and sequencing of structural variation from eight human genomes. Nature 453:56-64.
153. Kim JI, Ju YS, Park H, Kim S, Lee S, Yi JH, Mudge J, Miller NA, Hong D, Bell CJ, Kim HS, Chung IS, Lee WC, Lee JS, Seo SH, Yun JY, Woo HN, Lee H, Suh D, Lee S, Kim HJ, Yavartanoo M, Kwak M, Zheng Y, Lee MK, Park H, Kim JY, Gokcumen O, Mills RE, Zaranek AW, Thakuria J, Wu X, Kim RW, Huntley JJ, Luo S, Schroth GP, Wu TD, Kim H, Yang KS, Park WY, Kim H, Church GM, Lee C, Kingsmore SF, Seo JS. 2009. A highly annotated whole-genome sequence of a Korean individual. Nature 460:1011-1015.
154. Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV, Gottesman MM. 2007. A "silent" polymorphism in the MDR1 gene changes substrate specificity. Science 315:525-528.
155. Kimura M. 1985. The role of compensatory neutral mutations in molecular evolution. J Genet 64:7-19.
156. Kleinjan DA, Lettice LA. 2008. Long-range gene control and genetic disease. Adv Genet 61:339-388.
157. Kleinjan DJ, Coutinho P. 2009. Cis-ruption mechanisms: disruption of cis-regulatory control as a cause of human genetic disease. Brief Funct Genomic Proteomic 8:317-332.
158. Klooster R, Straasheijm K, Shah B, Sowden J, Frants R, Thornton C, Tawil R, van der Maarel S. 2009. Comprehensive expression analysis of FSHD candidate genes at the mRNA and protein level. Eur J Hum Genet 17:1615-1624.
159. Koenig SC, Becirevic E, Hellberg MS, Li MY, So JC, Hankins JS, Ware RE, McMahon L, Steinberg MH, Luo HY, Chui DH. 2009. Sickle cell disease caused by heterozygosity for Hb S and novel LCR deletion: Report of two patients. Am J Hematol 84:603-606.
160. Kondrashov AS, Sunyaev S, Kondrashov FA. 2002. Dobzhansky-Muller incompatibilities in protein evolution. Proc Natl Acad Sci USA 99:14878-14883.
161. Krawczak M, Thomas NS, Hundrieser B, Mort M, Wittig M, Hampe J, Cooper DN. 2007. Single base-pair substitutions in exon-intron junctions of human genes: nature, distribution, and consequences for mRNA splicing. Hum Mutat 28:150-158.
162. Kryukov GV, Pennacchio LA, Sunyaev SR. 2007. Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. Am J Hum Genet 80:727-739.
163. Kryukov GV, Schmidt S, Sunyaev S. 2005. Small fitness effect of mutations in highly conserved non-coding regions. Hum Mol Genet 14:2221-2229.
164. Kryukov GV, Shpunt A, Stamatoyannopoulos JA, Sunyaev SR. 2009. Power of deep, all-exon resequencing for discovery of human trait genes. Proc Natl Acad Sci USA 106:3871-3876.
165. Kumar S, Suleski MP, Markov GJ, Lawrence S, Marco A, Filipski AJ. 2009. Positional conservation and amino acids shape the correct diagnosis and population frequencies of benign and damaging personal amino acid mutations. Genome Res 19:1562-1569.
166. Kwan T, Benovoy D, Dias C, Gurd S, Provencher C, Beaulieu P, Hudson TJ, Sladek R, Majewski J. 2008. Genome-wide analysis of transcript isoform variation in humans. Nat Genet 40:225-231.
167. Lage K, Hansen NT, Karlberg EO, Eklund AC, Roque FS, Donahoe PK, Szallasi Z, Jensen TS, Brunak S. 2008. A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes. Proc Natl Acad Sci USA 105:20870-20875.
168. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann N, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blöcker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowski J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ, International Human Genome Sequencing Consortium. 2001. Initial sequencing and analysis of the human genome. Nature 409:860-921.
169. Lauderdale JD, Wilensky JS, Oliver ER, Walton DS, Glaser T. 2000. 3′ deletions cause aniridia by preventing PAX6 gene expression. Proc Natl Acad Sci USA 97:13755-13759.
170. Lecointre C, Pichon O, Hamel A, Heloury Y, Michel-Calemard L, Morel Y, David A, Le Caignec C. 2009. Familial acampomelic form of campomelic dysplasia caused by a 960 kb deletion upstream of SOX9. Am J Med Genet 149A:1183-1189.
171. Lee C, Scherer SW. 2010. The clinical context of copy number variation in the human genome. Expert Rev Mol Med 12:e8.
172. Lettice LA, Heaney SJ, Purdie LA, Li L, de Beer P, Oostra BA, Goode D, Elgar G, Hill RE, de Graaff E. 2003. A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum Mol Genet 12:1725-1735.
173. Lettice LA, Horikoshi T, Heaney SJ, van Baren MJ, van der Linde HC, Breedveld GJ, Joosse M, Akarsu N, Oostra BA, Endo N, Shibata M, Suzuki M, Takahashi E, Shinka T, Nakahori Y, Ayusawa D, Nakabayashi K, Scherer SW, Heutink P, Hill RE, Noji S. 2002. Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly. Proc Natl Acad Sci USA 99:7548-7553.
174. Levy S, Sutton G, Ng PC, Feuk L, Halpern AL, Walenz BP, Axelrod N, Huang J, Kirkness EF, Denisov G, Lin Y, MacDonald JR, Pang AW, Shago M, Stockwell TB, Tsiamouri A, Bafna V, Bansal V, Kravitz SA, Busam DA, Beeson KY, McIntosh TC, Remington KA, Abril JF, Gill J, Borman J, Rogers YH, Frazier ME, Scherer SW, Strausberg RL, Venter JC. 2007. The diploid genome sequence of an individual human. PLoS Biol 5:e254.
175. Lewinsky RH, Jensen TG, Møller J, Stensballe A, Olsen J, Troelsen JT. 2005. T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro. Hum Mol Genet 14:3945-3953.
176. Li B, Krishnan VG, Mort ME, Xin F, Kamati KK, Cooper DN, Mooney SD, Radivojac P. 2009a. Automated inference of molecular mechanisms of disease from amino acid substitutions. Bioinformatics 25:2744-2750.
177. Li H, Xie H, Liu W, Hu R, Huang B, Tan YF, Xu K, Sheng ZF, Zhou HD, Wu XP, Luo XH. 2009d. A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans. J Clin Invest 119:3666-3677.
178. Li JB, Levanon EY, Yoon JK, Aach J, Xie B, Leproust E, Zhang K, Gao Y, Church GM. 2009b. Genome-wide identification of human RNA editing sites by parallel DNA capturing and sequencing. Science 324:1210-1213.
179. Li R, Li Y, Zheng H, Luo R, Zhu H, Li Q, Qian W, Ren Y, Tian G, Li J, Zhou G, Zhu X, Wu H, Qin J, Jin X, Li D, Cao H, Hu X, Blanche H, Cann H, Zhang X, Li S, Bolund L, Kristiansen K, Yang H, Wang J, Wang J. 2010a. Building the sequence map of the human pan-genome. Nat Biotechnol 28:57-63.
180. Li SC, Chan WC, Hu LY, Lai CH, Hsu CN, Lin WC. 2010b. Identification of homologous microRNAs in 56 animal genomes. Genomics (in press).
181. Li W, Duan R, Kooy F, Sherman SL, Zhou W, Jin P. 2009c. Germline mutation of microRNA-125a is associated with breast cancer. J Med Genet 46:358-360.
182. Li YC, Korol AB, Fahima T, Nevo E. 2004. Microsatellites within genes: structure, function, and evolution. Mol Biol Evol 21:991-1007.
183. Liang H, Li W-H. 2009. Functional compensation by duplicated genes in mouse. Trends Genet 25:441-442.
184. Liao BY, Zhang J. 2008. Null mutations in human and mouse orthologs frequently result in different phenotypes. Proc Natl Acad Sci USA 105:6987-6992.
185. Licastro D, Gennarino VA, Petrera F, Sanges R, Banfi S, Stupka E. 2010. Promiscuity of enhancer, coding and non-coding transcription functions in ultraconserved elements. BMC Genomics 11:151.
186. Lin L, Jiang P, Shen S, Sato S, Davidson BL, Xing Y. 2009. Large-scale analysis of exonized mammalian-wide interspersed repeats in primate genomes. Hum Mol Genet 18:2204-2214.
187. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR. 2009. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462:315-322.
188. Liu JC, Makova KD, Adkins RM, Gibson S, Li WH. 2001. Episodic evolution of growth hormone in primates and emergence of the species specificity of human growth hormone receptor. Mol Biol Evol 18:945-953. (Pubitemid 32520466)
189. Liu W, Sun J, Li G, Zhu Y, Zhang S, Kim ST, Sun J, Wiklund F, Wiley K, Isaacs SD, Stattin P, Xu J, Duggan D, Carpten JD, Isaacs WB, Grönberg H, Zheng SL, Chang BL. 2009. Association of a germ-line copy number variation at 2p24.3 and risk for aggressive prostate cancer. Cancer Res 69: 2176-2179.
190. Lohmueller KE, Indap AR, Schmidt S, Boyko AR, Hernandez RD, Hubisz MJ, Sninsky JJ, White TJ, Sunyaev SR, Nielsen R, Clark AG, Bustamante CD. 2008. Proportionally more deleterious genetic variation in European than in African populations. Nature 451:994-997.
191. Lomelin D, Jorgenson E, Risch N. 2010. Human genetic variation recognizes functional elements in non-coding sequence. Genome Res 20:311-319.
192. López-Bigas N, Audit B, Ouzounis C, Parra G, Guigó R. 2005. Are splicing mutations the most frequent cause of hereditary disease? FEBS Lett 579:1900-1903.
193. López-Bigas N, Blencowe BJ, Ouzounis CA. 2006. Highly consistent patterns for inherited human diseases at the molecular level. Bioinformatics 22:269-277.
194. López-Bigas N, Ouzounis CA. 2004. Genome-wide identification of genes likely to be involved in human genetic disease. Nucleic Acids Res 32:3108-3114.
195. Louro R, Smirnova AS, Verjovski-Almeida S. 2009. Long intronic noncoding RNA transcription: expression noise or expression choice? Genomics 93:291-298.
196. Lowe CB, Bejerano G, Haussler D. 2007. Thousands of human mobile element fragments undergo strong purifying selection near developmental genes. Proc Natl Acad Sci USA 104:8005-8010.
197. Lower KM, Hughes JR, De Gobbi M, Henderson S, Viprakasit V, Fisher C, Goriely A, Ayyub H, Sloane-Stanley J, Vernimmen D, Langford C, Garrick D, Gibbons RJ, Higgs DR. 2009. Adventitious changes in long-range gene expression caused by polymorphic structural variation and promoter competition. Proc Natl Acad Sci USA 106:21771-21776.
198. Lualdi S, Tappino B, Di Duca M, Dardis A, Anderson CJ, Biassoni R, Thompson PW, Corsolini F, Di Rocco M, Bembi B, Regis S, Cooper DN, Filocamo M. 2010. Enigmatic in vivo iduronate-2-sulfatase (IDS) mutant transcript correction to wild-type in Hunter syndrome. Hum Mutat 31:E1261-E1285.
199. Luco RF, Pan Q, Tominaga K, Blencowe BJ, Pereira-Smith OM, Misteli T. 2010. Regulation of alternative splicing by histone modifications. Science 327:996-1000.
200. Lupski JR, Reid JG, Gonzaga-Jauregui C, Rio Deiros D, Chen DC, Nazareth L, Bainbridge M, Dinh H, Jing C, Wheeler DA, McGuire AL, Zhang F, Stankiewicz P, Halperin JJ, Yang C, Gehman C, Guo D, Irikat RK, Tom W, Fantin NJ, Muzny DM, Gibbs RA. 2010. Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. New Engl J Med 362:1181-1191.
201. Lynch M. 2010. Rate, molecular spectrum, and consequences of human mutation. Proc Natl Acad Sci USA 107:961-968.
202. McCarroll SA. 2008. Extending genome-wide association studies to copy-number variation. Hum Mol Genet 17(R2):R135-142.
203. McKernan KJ, Peckham HE, Costa GL, McLaughlin SF, Fu Y, Tsung EF, Clouser CR, Duncan C, Ichikawa JK, Lee CC, Zhang Z, Ranade SS, Dimalanta ET, Hyland FC, Sokolsky TD, Zhang L, Sheridan A, Fu H, Hendrickson CL, Li B, Kotler L, Stuart JR, Malek JA, Manning JM, Antipova AA, Perez DS, Moore MP, Hayashibara KC, Lyons MR, Beaudoin RE, Coleman BE, Laptewicz MW, Sannicandro AE, Rhodes MD, Gottimukkala RK, Yang S, Bafna V, Bashir A, MacBride A, Alkan C, Kidd JM, Eichler EE, Reese MG, De La Vega FM, Blanchard AP. 2009. Sequence and structural variation in a human genome uncovered by short-read, massively parallel ligation sequencing using two-base encoding. Genome Res 19:1527-1541.
204. McLean C, Bejerano G. 2008. Dispensability of mammalian DNA. Genome Res 18:1743-1751.
205. Mann V, Hobson EE, Li B, Stewart TL, Grant SF, Robins SP, Aspden RM, Ralston SH. 2001. A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 107:899-907. (Pubitemid 32274043)
206. Martin MM, Buckenberger JA, Jiang J, Malana GE, Nuovo GJ, Chotani M, Feldman DS, Schmittgen TD, Elton TS. 2007. The human angiotensin II type 1 receptor 11+66 A/C polymorphism attenuates microrna-155 binding. J Biol Chem 282:24262-24269.
207. Maston GA, Evans SK, Green MR. 2006. Transcriptional regulatory elements in the human genome. Annu Rev Genomics Hum Genet 7:29-59.
208. Mattick JS. 2009. The genetic signatures of noncoding RNAs. PloS Genet 5:e1000459.
209. Medvedeva YA, Fridman MV, Oparina NJ, Malko DB, Ermakova EO, Kulakovskiy IV, Heinzel A, Makeev VJ. 2010. Intergenic, gene terminal, and intragenic CpG islands in the human genome. BMC Genomics 11:48.
210. Mefford HC. 2009. Genotype to phenotype-discovery and characterization of novel genomic disorders in a "genotype-first" era. Genet Med 11:836-842.
211. Mefford HC, Eichler EE. 2009. Duplication hotspots, rare genomic disorders, and common disease. Curr Opin Genet Dev 19:196-204.
212. Mencía A, Modamio-Hłybjør S, Redshaw N, Morín M, Mayo-Merino F, Olavarrieta L, Aguirre LA, del Castillo I, Steel KP, Dalmay T, Moreno F, Moreno-Pelayo MA. 2009. Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss. Nat Genet 41: 609-613.
213. Mercer TR, Dinger ME, Mattick JS. 2009. Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155-159.
214. Merikangas AK, Corvin AP, Gallagher L. 2009. Copy-number variants in neurodevelopmental disorders: promises and challenges. Trends Genet 25:536-544.
215. Miller MP, Kumar S. 2001. Understanding human disease mutations through the use of interspecific genetic variation. Hum Mol Genet 10:2319-2328. (Pubitemid 33069538)
216. Miller MP, Parker JD, Rissing SW, Kumar S. 2003. Quantifying the intragenic distribution of human disease mutations. Ann Hum Genet 67:567-579. (Pubitemid 38016717)
217. Mills RE, Bennett EA, Iskow RC, Devine SE. 2007. Which transposable elements are active in the human genome? Trends Genet 23:183-191.
218. Morley M, Molony CM, Weber TM, Devlin JL, Ewens KG, Spielman RS, Cheung VG. 2004. Genetic analysis of genome-wide variation in human gene expression. Nature 430:743-747.
219. Morris JA. 2001. How many deleterious mutations are there in the human genome? Med Hypotheses 56:646-652.
220. Mort M, Evani US, Krishnan VG, Kamati KK, Baenziger PH, Bagchi A, Peters B, Sathyesh R, Li B, Sun Y, Xue B, Shah N, Kann M, Cooper DN, Radivojac P, Mooney SD. 2010. In silico functional profiling of human disease-associated and polymorphic amino acid substitutions. Hum Mutat 31:335-346.
221. Nackley AG, Shabalina SA, Lambert JE, Conrad MS, Gibson DG, Spiridonov AN, Satterfield SK, Diatchenko L. 2009. Low enzymatic activity haplotypes of the human catechol-O-methyltransferase gene: enrichment for marker SNPs. PLoS One 4:e5237.
222. Nackley AG, Shabalina SA, Tchivileva IE, Satterfield K, Korchynskyi O, Makarov SS, Maixner W, Diatchenko L. 2006. Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science 314:1930-1933.
223. Ng PC, Henikoff S. 2006. Predicting the effects of amino acid substitutions on protein function. Annu Rev Genomics Hum Genet 7:61-80. (Pubitemid 44627922)
224. Ng PC, Levy S, Huang J, Stockwell TB, Walenz BP, Li K, Axelrod N, Busam DA, Strausberg RL, Venter JC. 2008. Genetic variation in an individual human exome. PLoS Genet 4:e1000160.
225. Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ. 2010. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet 42:30-35.
226. 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. 2009. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 461:272-276.
227. 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. 2010. Next-generation sequencing of a 40Mb linkage interval reveals TSPAN12 mutations in patients with familial exudative vitreoretino-athy. Am J Hum Genet 86:240-247.
228. Nishihara H, Smit AF, Okada N. 2006. Functional noncoding sequences derived from SINEs in the mammalian genome. Genome Res 16:864-874.
229. Nozu K, Iijima K, Nozu Y, Ikegami E, Imai T, Fu XJ, Kaito H, Nakanishi K, Yoshikawa N, Matsuo M. 2009. A deep intronic mutation in the SLC12A3 gene leads to Gitelman syndrome. Pediatr Res 66:590-593.
230. Ogino W, Takeshima Y, Nishiyama A, Okizuka Y, Yagi M, Tsuneishi S, Saiki K, Kugo M, Matsuo M. 2007. Mutation analysis of the ornithine transcarbamylase (OTC) gene in five Japanese OTC deficiency patients revealed two known and three novel mutations including a deep intronic mutation. Kobe J Med Sci 53:229-240.
231. Olds LC, Sibley E. 2003. Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element. Hum Mol Genet 12:2333-2340.
232. Orkin SH, Alter BP, Altay C, Mahoney MJ, Lazarus H, Hobbins JC, Nathan DG. 1978. Application of endonuclease mapping to the analysis and prenatal diagnosis of thalassemias caused by globin-gene deletion. N Engl J Med 299:166-172. (Pubitemid 8396222)
233. Osada N, Mano S, Gojobori J. 2009. Quantifying dominance and deleterious effect on human disease genes. Proc Natl Acad Sci USA 106:841-846.
234. Ovcharenko I, Loots GG, Nobrega MA, Hardison RC, Miller W, Stubbs L. 2005. Evolution and functional classification of vertebrate gene deserts. Genome Res 15:137-145.
235. Ozsolak F, Platt AR, Jones DR, Reifenberger JG, Sass LE, McInerney P, Thompson JF, Bowers J, Jarosz M, Milos PM. 2009. Direct RNA sequencing. Nature 461:814-818.
236. Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. 2008. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet 40:1413-1415.
237. Park D, Park J, Park SG, Park T, Choi SS. 2008. Analysis of human disease genes in the context of gene essentiality. Genomics 92:414-418.
238. Park PJ. 2009. ChIP-seq: advantages and challenges of a maturing technology. Nat Rev Genet 10:669-680.
239. Parker SC, Hansen L, Abaan HO, Tullius TD, Margulies EH. 2009. Local DNA topography correlates with functional noncoding regions of the human genome. Science 324:389-392.
240. Parra G, Reymond A, Dabbouseh N, Dermitzakis ET, Castelo R, Thomson TM, Antonarakis SE, Guigó R. 2006. Tandem chimerism as a means to increase protein complexity in the human genome. Genome Res 16:37-44.
241. Pastinen T, Ge B, Hudson TJ. 2006. Influence of human genome polymorphism on gene expression. Hum Mol Genet 15 Spec No 1:R9-R16.
242. Pennacchio LA, Ahituv N, Moses AM, Prabhakar S, Nobrega MA, Shoukry M, Minovitsky S, Dubchak I, Holt A, Lewis KD, Plajzer-Frick I, Akiyama J, De Val S, Afzal V, Black BL, Couronne O, Eisen MB, Visel A, Rubin EM. 2006. In vivo enhancer analysis of human conserved non-coding sequences. Nature 444:499-502.
243. Perotti D, De Vecchi G, Testi MA, Lualdi E, Modena P, Mondini P, Ravagnani F, Collini P, Di Renzo F, Spreafico F, Terenziani M, Sozzi G, Fossati-Bellani F, Radice P. 2004. Germline mutations of the POU6F2 gene in Wilms tumors with loss of heterozygosity on chromosome 7p14. Hum Mutat 24:400-407.
244. Pesole G. 2008. What is a gene? An updated operational definition. Gene 417:1-4.
245. Peters BA, St Croix B, Sjö T, Cummins JM, Silliman N, Ptak J, Saha S, Kinzler KW, Hatzis C, Velculescu VE. 2007. Large-scale identification of novel transcripts in the human genome. Genome Res 17:287-292.
246. Pheasant M, Mattick JS. 2007. Raising the estimate of functional human sequences. Genome Res 17:1245-1253.
247. Piriyapongsa J, Mariño-Ramírez L, Jordan IK. 2007. Origin and evolution of human microRNAs from transposable elements. Genetics 176:1323-1337. (Pubitemid 46961124)
248. Pomerantz MM, Ahmadiyeh N, Jia L, Herman P, Verzi MP, Doddapaneni H, Beckwith CA, Chan JA, Hills A, Davis M, Yao K, Kehoe SM, Lenz HJ, Haiman CA, Yan C, Henderson BE, Frenkel B, Barretina J, Bass A, Tabernero J, Baselga J, Regan MM, Manak JR, Shivdasani R, Coetzee GA, Freedman ML. 2009. The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat Genet 41:882-884.
249. Ponjavic J, Ponting CP, Lunter G. 2007. Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs. Genome Res 17:556-565.
250. Ponting CP, Lunter G. 2006. Signatures of adaptive evolution within human noncoding sequence. Hum Mol Genet 15:R170-R175.
251. Poon A, Davis BH, Chao L. 2005. The coupon collector and the suppressor mutation: estimating the number of compensatory mutations by maximum likelihood. Genetics 170:1323-1332.
252. Prabhakar S, Noonan JP, Pääbo S, Rubin EM. 2006. Accelerated evolution of conserved noncoding sequences in humans. Science 314:786.
253. Prabhu S, Pe'er I. 2009. Overlapping pools for high-throughput targeted resequencing. Genome Res 19:1254-1261.
254. Preker P, Nielsen J, Kammler S, Lykke-Andersen S, Christensen MS, Mapendano CK, Schierup MH, Jensen TH. 2008. RNA exosome depletion reveals transcription upstream of active human promoters. Science 322:1851-1854.
255. Pros E, Gómez C, Martí T, Fábregas P, Serra E, Lázaro C. 2008. Nature and mRNA effect of 282 different NF1 point mutations: focus on splicing alterations. Hum Mutat 29:E173-E193.
256. Pruitt KD, Harrow J, Harte RA, Wallin C, Diekhans M, Maglott DR, Searle S, Farrell CM, Loveland JE, Ruef BJ, Hart E, Suner MM, Landrum MJ, Aken B, Ayling S, Baertsch R, Fernandez-Banet J, Cherry JL, Curwen V, Dicuccio M, Kellis M, Lee J, Lin MF, Schuster M, Shkeda A, Amid C, Brown G, Dukhanina O, Frankish A, Hart J, Maidak BL, Mudge J, Murphy MR, Murphy T, Rajan J, Rajput B, Riddick LD, Snow C, Steward C, Webb D, Weber JA, Wilming L, Wu W, Birney E, Haussler D, Hubbard T, Ostell J, Durbin R, Lipman D. 2009. The consensus coding sequence (CCDS) project: identifying a common protein-coding gene set for the human and mouse genomes. Genome Res 19:1316-1323.
257. Purevsuren J, Fukao T, Hasegawa Y, Fukuda S, Kobayashi H, Yamaguchi S. 2008. Study of deep intronic sequence exonization in a Japanese neonate with a mitochondrial trifunctional protein deficiency. Mol Genet Metab 95:46-51.
258. Quemener S, Chen JM, Chuzhanova N, Bénech C, Casals T, MacekJr M, Bienvenu T, McDevitt T, Farrell PM, Loumi O, Messaoud T, Cuppens H, Cutting GR, Stenson PD, Giteau K, Audrézet MP, Cooper DN, Férec C. 2010. Complete ascertainment of intragenic copy number mutations (CNMs) in the CFTR gene and its implications for CNM formation at other autosomal loci. Hum Mutat 31:421-428.
259. Rademakers R, Eriksen JL, Baker M, Robinson T, Ahmed Z, Lincoln SJ, Finch N, Rutherford NJ, Crook RJ, Josephs KA, Boeve BF, Knopman DS, Petersen RC, Parisi JE, Caselli RJ, Wszolek ZK, Uitti RJ, Feldman H, Hutton ML, Mackenzie IR, Graff-Radford NR, Dickson DW. 2008. Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia. Hum Mol Genet 17:3631-3642.
260. Rahimov F, Marazita ML, Visel A, Cooper ME, Hitchler MJ, Rubini M, Domann FE, Govil M, Christensen K, Bille C, Melbye M, Jugessur A, Lie RT, Wilcox AJ, Fitzpatrick DR, Green ED, Mossey PA, Little J, Steegers-Theunissen RP, Pennacchio LA, Schutte BC, Murray JC. 2008. Disruption of an AP-2α binding site in an IRF6 enhancer is associated with cleft lip. Nat Genet 40:1341-1347.
261. Rasmussen M, Li Y, Lindgreen S, Pedersen JS, Albrechtsen A, Moltke I, Metspalu M, Metspalu E, Kivisild T, Gupta R, Bertalan M, Nielsen K, Gilbert MT, Wang Y, Raghavan M, Campos PF, Kamp HM, Wilson AS, Gledhill A, Tridico S, Bunce M, Lorenzen ED, Binladen J, Guo X, Zhao J, Zhang X, Zhang H, Li Z, Chen M, Orlando L, Kristiansen K, Bak M, Tommerup N, Bendixen C, Pierre TL, Grønnow B, Meldgaard M, Andreasen C, Fedorova SA, Osipova LP, Higham TF, Ramsey CB, Hansen TV, Nielsen FC, Crawford MH, Brunak S, Sicheritz-Pontén T, Villems R, Nielsen R, Krogh A, Wang J, Willerslev E. 2010. Ancient human genome sequence of an extinct Palaeo-Eskimo. Nature 463:757-762.
262. Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH, Andrews TD, FieglerH, Shapero MH, Carson AR, Chen W, Cho EK, Dallaire S, Freeman JL, González JR, Gratacòs M, Huang J, Kalaitzopoulos D, Komura D, MacDonald JR, Marshall CR, Mei R, Montgomery L, Nishimura K, Okamura K, Shen F, Somerville MJ, Tchinda J, Valsesia A,Woodwark C, Yang F, Zhang J, Zerjal T, Zhang J, Armengol L, Conrad DF, Estivill X, Tyler-Smith C, Carter NP, Aburatani H, Lee C, Jones KW, Scherer SW, Hurles ME. 2006. Global variation in copy number in the human genome. Nature 444:444-454.
263. Reich DE, Lander ES. 2001. On the allelic spectrum of human disease. Trends Genet 17:502-510.
264. Rio Frio T, McGee TL, Wade NM, Iseli C, Beckmann JS, Berson EL, Rivolta C. 2009. A single-base substitution within an intronic repetitive element causes dominant retinitis pigmentosa with reduced penetrance. Hum Mutat 30:1340-1347.
265. Rincón A, Aguado C, Desviat LR, Sánchez-Alcudia R, Ugarte M, Pérez B. 2007. Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA. Am J Hum Genet 81:1262-1270.
266. Roach JC, Glusman G, Smit AF, Huff CD, Hubley R, Shannon PT, Rowen L, Pant KP, Goodman N, Bamshad M, Shendure J, Drmanac R, Jorde LB, Hood L, Galas DJ. 2010. Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science 328:636-639.
267. Romao L, Osorio-Almeida L, Higgs DR, Lavinha J, Liebhaber SA. 1991. α-Thalassemia resulting from deletion of regulatory sequences far upstream of the alpha-globin structural genes. Blood 78:1589-1595.
268. Rozowsky JS, Newburger D, Sayward F, Wu J, Jordan G, Korbel JO, Nagalakshmi U, Yang J, Zheng D, Guigó R, Gingeras TR, Weissman S, Miller P, Snyder M, Gerstein MB. 2007. The DART classification of unannotated transcription within the ENCODE regions: associating transcription with known and novel loci. Genome Res 17:732-745.
269. Rung J, Cauchi S, Albrechtsen A, Shen L, Rocheleau G, Cavalcanti-Proenc-a C, Bacot F, Balkau B, Belisle A, Borch-Johnsen K, Charpentier G, Dina C, Durand E, Elliott P, Hadjadj S, Jäin MR, Laitinen J, Lauritzen T, Marre M, Mazur A, Meyre D, Montpetit A, Pisinger C, Posner B, Poulsen P, Pouta A, Prentki M, Ribel-Madsen R, Ruokonen A, Sandbaek A, Serre D, Tichet J, Vaxillaire M, Wojtaszewski JF, Vaag A, Hansen T, Polychronakos C, Pedersen O, Froguel P, Sladek R. 2009. Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Nat Genet 41:1110-1115.
270. Sahoo T, del Gaudio D, German JR, Shinawi M, Peters SU, Person RE, Garnica A, Cheung SW, Beaudet AL. 2008. Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster. Nat Genet 40:719-721.
271. Sakai H, Koyanagi KO, Imanishi T, Itoh T, Gojobori T. 2007. Frequent
272. Sanford JR, Wang X, Mort M, Vanduyn N, Cooper DN, Mooney SD, Edenberg HJ, Liu Y. 2009. Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts. Genome Res 19:381-394.
273. Schalkwyk LC, Meaburn EL, Smith R, Dempster EL, Jeffries AR, Davies MN, Plomin R, Mill J. 2010. Allelic skewing of DNA methylation is widespread across the genome. Am J Hum Genet 86:196-212.
274. Schollen E, Keldermans L, Foulquier F, Briones P, Chabas A, Sánchez-Valverde F, Adamowicz M, Pronicka E, Wevers R, Matthijs G. 2007. Characterization of two unusual truncating PMM2 mutations in two CDG-Ia patients. Mol Genet Metab 90:408-413.
275. Schork NJ, Murray SS, Frazer KA, Topol EJ. 2009. Common vs. rare allele hypotheses for complex diseases. Curr Opin Genet Dev 19:212-219.
276. Schuster SC, Miller W, Ratan A, Tomsho LP, Giardine B, Kasson LR, Harris RS, Petersen DC, Zhao F, Qi J, Alkan C, Kidd JM, Sun Y, Drautz DI, Bouffard P, Muzny DM, Reid JG, Nazareth LV, Wang Q, Burhans R, Riemer C, Wittekindt NE, Moorjani P, Tindall EA, Danko CG, Teo WS, Buboltz AM, Zhang Z, Ma Q, Oosthuysen A, Steenkamp AW, Oostuisen H, Venter P, Gajewski J, Zhang Y, Pugh BF, Makova KD, Nekrutenko A, Mardis ER, Patterson N, Pringle TH, Chiaromonte F, Mullikin JC, Eichler EE, Hardison RC, Gibbs RA, Harkins TT, Hayes VM. 2010. Complete Khoisan and Bantu genomes from southern Africa. Nature 463:943-947.
277. Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yoon S, Krasnitz A, Kendall J, Leotta A, Pai D, Zhang R, Lee YH, Hicks J, Spence SJ, Lee AT, Puura K, Lehtimäki T, Ledbetter D, Gregersen PK, Bregman J, Sutcliffe JS, Jobanputra V, Chung W, Warburton D, King MC, Skuse D, Geschwind DH, Gilliam TC, Ye K, Wigler M. 2007. Strong association of de novo copy number mutations with autism. Science 316:445-449.
278. Sebat J, Lakshmi B, Troge J, Alexander J, Young J, Lundin P, Mo̊nér S, Massa H, Walker M, Chi M, Navin N, Lucito R, Healy J, Hicks J, Ye K, Reiner A, Gilliam TC, Trask B, Patterson N, Zetterberg A, Wigler M. 2004. Large-scale copy number polymorphism in the human genome. Science 305:525-528.
279. Seila AC, Calabrese JM, Levine SS, Yeo GW, Rahl PB, Flynn RA, Young RA, Sharp PA. 2008. Divergent transcription from active promoters. Science 322:1849-1851.
280. Sethupathy P, Collins FS. 2008. MicroRNA target site polymorphisms and human disease. Trends Genet 24:489-497.
281. Shao X, Shepelev V, Fedorov A. 2006. Bioinformatic analysis of exon repetition, exon scrambling and trans-splicing in humans. Bioinformatics 22:692-698.
282. Shen J, Ambrosone CB, Zhao H. 2009. Novel genetic variants in microRNA genes and familial breast cancer. Int J Cancer 124:1178-1182.
283. Shen J, DiCioccio R, Odunsi K, Lele SB, Zhao H. 2010. Novel genetic variants in miR-191 gene and familial ovarian cancer. BMC Cancer 10:47.
284. Shlien A, Tabori U, Marshall CR, Pienkowska M, Feuk L, Novokmet A, Nanda S, Druker H, Scherer SW, Malkin D. 2008. Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome. Proc Natl Acad Sci USA 105:11264-11269.
285. Simon D, Laloo B, Barillot M, Barnetche T, Blanchard C, Rooryck C, Marche M, Burgelin I, Coupry I, Chassaing N, Gilbert-Dussardier B, Lacombe D, Grosset C, Arveiler B. 2010. A mutation in the 3′-UTR of the HDAC6 gene abolishing the post-transcriptional regulation mediated by hsa-miR-433 is linked to a new form of dominant X-linked chondrodysplasia. Hum Mol Genet 19:2015-2027.
286. Smith NG, Eyre-Walker A. 2003. Human disease genes: patterns and predictions. Gene 318:169-175.
287. Smith AD, Xuan Z, Zhang MQ. 2008. Using quality scores and longer reads improves accuracy of Solexa read mapping. BMC Bioinformatics 9:128.
288. Snider L, Asawachaicharn A, Tyler AE, Geng LN, Petek LM, Maves L, Miller DG, Lemmers RJ, Winokur ST, Tawil R, van der Maarel SM, Filippova GN, Tapscott SJ. 2009. RNA transcripts, miRNA-sized fragments and proteins produced from D4Z4 units: new candidates for the pathophysiology of facioscapulohumeral dystrophy. Hum Mol Genet 18:2414-2430.
289. Snyder M, Du J, Gerstein M. 2010. Personal genome sequencing: current approaches and challenges. Genes Dev 24:423-431.
290. Solis AS, Shariat N, Patton JG. 2008. Splicing fidelity, enhancers, and disease. Front Biosci 13:1926-1942.
291. Spena S, Asselta R, Platé M, Castaman G, Duga S, Tenchini ML. 2007. Pseudo-exon activation caused by a deep-intronic mutation in the fibrinogen gamma-chain gene as a novel mechanism for congenital afibrinogenaemia. Br J Haematol 139:128-132.
292. Stankiewicz P, Sen P, Bhatt SS, Storer M, Xia Z, Bejjani BA, Ou Z, Wiszniewska J, Driscoll DJ, Maisenbacher MK, Bolivar J, Bauer M, Zackai EH, McDonald-McGinn D, Nowaczyk MM, Murray M, Hustead V, Mascotti K, Schultz R, Hallam L, McRae D, Nicholson AG, Newbury R, Durham-O'Donnell J, Knight G, Kini U, Shaikh TH, Martin V, Tyreman M, Simonic I, Willatt L, Paterson J, Mehta S, Rajan D, Fitzgerald T, Gribble S, Prigmore E, Patel A, Shaffer LG, Carter NP, Cheung SW, Langston C, Shaw-Smith C. 2009. Genomic and genic deletions of the FOX gene cluster on 16q24.1 and inactivating mutations of FOXF1 cause alveolar capillary dysplasia and other malformations. Am J Hum Genet 84:780-791.
293. Stankiewicz P, Lupski JR. 2010. Structural variation in the human genome and its role in disease. Annu Rev Med 61:437-455.
294. Stefansson H, Rujescu D, Cichon S, Pietiläinen OP, Ingason A, Steinberg S, Fossdal R, Sigurdsson E, Sigmundsson T, Buizer-Voskamp JE, Hansen T, Jakobsen KD, Muglia P, Francks C, Matthews PM, Gylfason A, Halldorsson BV, Gudbjartsson D, Thorgeirsson TE, Sigurdsson A, Jonasdottir A, Jonasdottir A, Bjornsson A, Mattiasdottir S, Blondal T, Haraldsson M, Magnusdottir BB, Giegling I, Möller HJ, Hartmann A, Shianna KV, Ge D, Need AC, Crombie C, Fraser G, Walker N, Lonnqvist J, Suvisaari J, Tuulio-Henriksson A, Paunio T, Toulopoulou T, Bramon E, Di Forti M, Murray R, Ruggeri M, Vassos E, Tosato S, Walshe M, Li T, Vasilescu C, Mühleisen TW, Wang AG, Ullum H, Djurovic S, Melle I, Olesen J, Kiemeney LA, Franke B; GROUP, Sabatti C, Freimer NB, Gulcher JR, Thorsteinsdottir U, Kong A, Andreassen OA, Ophoff RA, Georgi A, Rietschel M, Werge T, Petursson H, Goldstein DB, Nöthen MM, Peltonen L, Collier DA, St Clair D, Stefansson K. 2008. Large recurrent microdeletions associated with schizophrenia. Nature 455:232-236.
295. Stenson PD, Mort M, Ball EV, Howells K, Phillips AD, Thomas NS, Cooper DN. 2009. The Human Gene Mutation Database: 2008 update. Genome Med 1:13.
296. Stranger BE, Forrest MS, Clark AG, Minichiello MJ, Deutsch S, Lyle R, Hunt S, Kahl B, Antonarakis SE, Tavaré S, Deloukas P, Dermitzakis ET. 2005. Genomewide associations of gene expression variation in humans. PLoS Genet 1:e78.
297. Stranger BE, Nica AC, Forrest MS, Dimas A, Bird CP, Beazley C, Ingle CE, Dunning M, Flicek P, Koller D, Montgomery S, Tavaré S, Deloukas P, Dermitzakis ET. 2007. Population genomics of human gene expression. Nat Genet 39:1217-1224.
298. Su Z, Gu X. 2008. Predicting the proportion of essential genes in mouse duplicates based on biased mouse knockout genes. J Mol Evol 67:705-709.
299. Subramanian S, Kumar S. 2006. Evolutionary anatomies of positions and types of disease-associated and neutral amino acid mutations in the human genome. BMC Genomics 7:306.
300. Sultan M, Schulz MH, 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 ML. 2008. A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science 321:956-960.
301. Sun G, Yan J, Noltner K, Feng J, Li H, Sarkis DA, Sommer SS, Rossi JJ. 2009. SNPs in human miRNA genes affect biogenesis and function. RNA 15:1640-1651.
302. Suriano G, Azevedo L, Novais M, Boscolo B, Seruca R, Amorim A, Ghibaudi EM. 2007. In vitro demonstration of intra-locus compensation using the ornithine transcarbamylase protein as model. Hum Mol Genet 16:2209-2214.
303. Susa S, Daimon M, Sakabe J, Sato H, Oizumi T, Karasawa S, Wada K, Jimbu Y, Kameda W, Emi M, Muramatsu M, Kato T. 2008. A functional polymorphism of the TNF-α gene that is associated with type 2 DM. Biochem Biophys Res Commun 369:943-947.
304. Svensson O, Arvestad L, Lagergren J. 2006. Genome-wide survey for biologically functional pseudogenes. PLoS Comput. Biol 2:e46.
305. Taft RJ, Glazov EA, Cloonan N, Simons C, Stephen S, Faulkner GJ, Lassmann T, Forrest AR, Grimmond SM, Schroder K, Irvine K, Arakawa T, Nakamura M, Kubosaki A, Hayashida K, Kawazu C, Murata M, Nishiyori H, Fukuda S, Kawai J, Daub CO, Hume DA, Suzuki H, Orlando V, Carninci P, Hayashizaki Y, Mattick JS. 2009. Tiny RNAs associated with transcription start sites in animals. Nat Genet 41:572-578.
306. Taylor J. 2005. Clues to function in gene deserts. Trends Biotechnol 23:269-271.
307. Terai G, Yoshizawa A, Okida H, Asai K, Mituyama T. 2010. Discovery of short pseudogenes derived from messenger RNAs. Nucleic Acids Res 38:1163-1171.
308. Thean LF, Loi C, Ho KS, Koh PK, Eu KW, Cheah PY. 2010. Genome-wide scan identifies a copy number variable region at 3q26 that regulates PPM1L in APC mutation-negative familial colorectal cancer patients. Genes Chrom Cancer 49:99-106.
309. Theuns J, Del-Favero J, Dermaut B, van Duijn CM, Backhovens H, Van den Broeck MV, Serneels S, Corsmit E, Van Broeckhoven CV, Cruts M. 2000. Genetic variability in the regulatory region of presenilin 1 associated with risk for Alzheimer's disease and variable expression. Hum Mol Genet 9:325-331.
310. Thornburg BG, Gotea V, Makałowski W. 2006. Transposable elements as a significant source of transcription regulating signals. Gene 365:104-110.
311. Tress ML, Martelli PL, Frankish A, Reeves GA, Wesselink JJ, Yeats C, Olason PI, Albrecht M, Hegyi H, Giorgetti A, Raimondo D, Lagarde J, Laskowski RA, López G, Sadowski MI, Watson JD, Fariselli P, Rossi I, Nagy A, Kai W, Størling Z, Orsini M, Assenov Y, Blankenburg H, Huthmacher C, Ramírez F, Schlicker A, Denoeud F, Jones P, Kerrien S, Orchard S, Antonarakis SE, Reymond A, Birney E, Brunak S, Casadio R, Guigo R, Harrow J, Hermjakob H, Jones DT, Lengauer T, Orengo CA, Patthy L, Thornton JM, Tramontano A, Valencia A. 2007. The implications of alternative splicing in the ENCODE protein complement. Proc Natl Acad.Sci USA 104:5495-5500.
312. Tsai CJ, Sauna ZE, Kimchi-Sarfaty C, Ambudkar SV, Gottesman MM, Nussinov R. 2008. Synonymous mutations and ribosome stalling can lead to altered folding pathways and distinct minima. J Mol Biol 383:281-291.
313. Tu Z, Wang L, Xu M, Zhou X, Chen T, Sun F. 2006. Further understanding human disease genes by comparing with housekeeping genes and other genes. BMC Genomics 7:31.
314. Tucker T, Marra M, Friedman JM. 2009. Massively parallel sequencing: the next big thing in genetic medicine. Am J Hum Genet 85:142-154.
315. Turgeon B, Meloche S. 2009. Interpreting neonatal lethal phenotypes in mouse mutants: insights into gene function and human diseases. Physiol Rev 89:1-26.
316. Tuupanen S, Turunen M, Lehtonen R, Hallikas O, Vanharanta S, Kivioja T, Björklund M, Wei G, Yan J, Niittymäki I, Mecklin JP, Järvinen H, Ristimäki A, Di-Bernardo M, East P, Carvajal-Carmona L, Houlston RS, Tomlinson I, Palin K, Ukkonen E, Karhu A, Taipale J, Aaltonen LA. 2009. The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nat Genet 41:885-890.
317. van Bokhoven H, Rawson RB, Merkx GF, Cremers FP, Seabra MC. 1996. cDNA cloning and chromosomal localization of the genes encoding the alpha- and beta-subunits of human Rab geranylgeranyl transferase: the 3′ end of the alpha-subunit gene overlaps with the transglutaminase 1 gene promoter. Genomics 38:133-140.
318. Velagaleti GV, Bien-Willner GA, Northup JK, Lockhart LH, Hawkins JC, Jalal SM, Withers M, Lupski JR, Stankiewicz P. 2005. Position effects due to chromosome breakpoints that map approximately 900 Kb upstream and approximately 1.3Mb downstream of SOX9 in two patients with campomelic dysplasia. Am J Hum Genet 76:652-662.
319. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, SkupskiM, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, HigginsME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F,Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, ZhangW, Zhang H, Zhao Q, Zheng L, Zhong F, ZhongW, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigó R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J,Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X. 2001. The sequence of the human genome. Science 291:1304-1351.
320. Venturin M, Moncini S, Villa V, Russo S, Bonati MT, Larizza L, Riva P. 2006. Mutations and novel polymorphisms in coding regions and UTRs of CDK5R1 and OMG genes in patients with non-syndromic mental retardation. Neurogenetics 7:59-66.
321. VerMilyea MD, O'Neill LP, Turner BM. 2009. Transcription-independent heritability of induced histone modifications in the mouse preimplantation embryo. PLoS One 4:e6086.
322. Veyrieras JB, Kudaravalli S, Kim SY, Dermitzakis ET, Gilad Y, Stephens M, Pritchard JK. 2008. High-resolution mapping of expression-QTLs yields insight into human gene regulation. PLoS Genet 4:e1000214.
323. Viprakasit V, Kidd AM, Ayyub H, Horsley S, Hughes J, Higgs DR. 2003. De novo deletion within the telomeric region flanking the human α-globin locus as a cause of α-thalassaemia. Br J Haematol 120:867-875.
324. Visel A, Rubin EM, Pennacchio LA. 2009. Genomic views of distant-acting enhancers. Nature 461:199-205.
325. Vuoristo JT, Berrettini WH, Ala-Kokko L. 2001. C18orf2, a novel, highly conserved intronless gene within intron 5 of the GNAL gene on chromosome 18p11. Cytogenet Cell Genet 93:19-22. (Pubitemid 32727537)
326. Waalen J, Beutler E. 2009. Genetic screening for low-penetrance variants in proteincoding genes. Annu Rev Genomics Hum Genet 10:431-450.
327. Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, Cooper GM, Nord AS, Kusenda M, Malhotra D, Bhandari A, Stray SM, Rippey CF, Roccanova P, Makarov V, Lakshmi B, Findling RL, Sikich L, Stromberg T, Merriman B, Gogtay N, Butler P, Eckstrand K, Noory L, Gochman P, Long R, Chen Z, Davis S, Baker C, Eichler EE, Meltzer PS, Nelson SF, Singleton AB, Lee MK, Rapoport JL, King MC, Sebat J. 2008. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320:539-543.
328. Walters RG, Jacquemont S, Valsesia A, de Smith AJ, Martinet D, Andersson J, Falchi M, Chen F, Andrieux J, Lobbens S, Delobel B, Stutzmann F, El-Sayed Moustafa JS, Chèvre JC, Lecoeur C, Vatin V, Bouquillon S, Buxton JL, Boute O, Holder-Espinasse M, Cuisset JM, Lemaitre MP, Ambresin AE, Brioschi A, Gaillard M, Giusti V, Fellmann F, Ferrarini A, Hadjikhani N, Campion D, Guilmatre A, Goldenberg A, Calmels N, Mandel JL, Le Caignec C, David A, Isidor B, Cordier MP, Dupuis-Girod S, Labalme A, Sanlaville D, Béri-Dexheimer M, Jonveaux P, Leheup B, Ounap K, Bochukova EG, Henning E, Keogh J, Ellis RJ, Macdermot KD, van Haelst MM, Vincent-Delorme C, Plessis G, Touraine R, Philippe A, Malan V, Mathieu-Dramard M, Chiesa J, Blaumeiser B, Kooy RF, Caiazzo R, Pigeyre M, Balkau B, Sladek R, Bergmann S, Mooser V, Waterworth D, Reymond A, Vollenweider P, Waeber G, Kurg A, Palta P, Esko T, Metspalu A, Nelis M, Elliott P, Hartikainen AL, McCarthy MI, Peltonen L, Carlsson L, Jacobson P, Sjöström L, Huang N, Hurles ME, O'Rahilly S, Farooqi IS, Männik K, Jarvelin MR, Pattou F, Meyre D, Walley AJ, Coin LJ, Blakemore AI, Froguel P, Beckmann JS. 2010. A new highly penetrant form of obesity due to deletions on chromosome 16p11.2. Nature 463:671-675.
329. Wang GS, Cooper TA. 2007. Splicing in disease: disruption of the splicing code and the decoding machinery. Nat Rev Genet 8:749-761.
330. 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 GK, Nielsen R, Durbin R, Bolund L, Zhang X, Li S, Yang H, Wang J. 2008a. The diploid genome sequence of an Asian individual. Nature 456:60-65.
331. Wang X, Wang K, Radovich M, Wang Y, Wang G, Feng W, Sanford JR, Liu Y. 2009a. Genome-wide prediction of cis-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing. BMC Genomics 10(Suppl 1):S4.
332. Wang Z, Gerstein M, Snyder M. 2009b. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet 10:57-63.
333. Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, Cui K, Roh TY, Peng W, Zhang MQ, Zhao K. 2008b. Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet 40:897-903.
334. Wang ZQ, Tian SH, Shi YZ, Zhou PT, Wang ZY, Shu RZ, Hu L, Kong X. 2007. A single C to T transition in intron 5 of LMBR1 gene is associated with triphalangeal thumb-polysyndactyly syndrome in a Chinese family. Biochem Biophys Res Commun 355:312-317.
335. Washietl S, Hofacker IL, Lukasser M, Hüttenhofer A, Stadler PF. 2005. Mapping of conserved RNA secondary structures predicts thousands of functional noncoding RNAs in the human genome. Nat Biotechnol 23:1383-1390.
336. Wen Y, Liu Y, Xu Y, Zhao Y, Hua R, Wang K, Sun M, Li Y, Yang S, Zhang XJ, Kruse R, Cichon S, Betz RC, Nöthen MM, van Steensel MA, van Geel M, Steijlen PM, Hohl D, Huber M, Dunnill GS, Kennedy C, Messenger A, Munro CS, Terrinoni A, Hovnanian A, Bodemer C, de Prost Y, Paller AS, Irvine AD, Sinclair R, Green J, Shang D, Liu Q, Luo Y, Jiang L, Chen HD, Lo WH, McLean WH, He CD, Zhang X. 2009. Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis. Nat Genet 41:228-233.
337. Werner A, Carlile M, Swan D. 2009. What do natural antisense transcripts regulate? RNA Biol 6:43-48.
338. Wheeler DA, Srinivasan M, Egholm M, Shen Y, Chen L, McGuire A, He W, Chen YJ, Makhijani V, Roth GT, Gomes X, Tartaro K, Niazi F, Turcotte CL, Irzyk GP, Lupski JR, Chinault C, Song XZ, Liu Y, Yuan Y, Nazareth L, Qin X, Muzny DM, Margulies M, Weinstock GM, Gibbs RA, Rothberg JM. 2008. The complete genome of an individual by massively parallel DNA sequencing. Nature 452:872-876.
339. Wieczorek D, Pawlik B, Li Y, Akarsu NA, Caliebe A, May KJ, Schweiger B, Vargas FR, Balci S, Gillessen-Kaesbach G, Wollnik B. 2010. A specific mutation in the distant sonic hedgehog (SHH) cis-regulator (ZRS) causes Werner mesomelic syndrome (WMS) while complete ZRS duplications underlie Haas type polysyndactyly and preaxial polydactyly (PPD) with or without triphalangeal thumb. Hum Mutat 31:81-89.
340. Wilch E, Azaiez H, Fisher RA, Elfenbein J, Murgia A, Birkenhäger R, Bolz H, da Silva- Costa SM, Del Castillo I, Haaf T, Hoefsloot L, Kremer H, Kubisch C, Le Marechal C, Pandya A, Sartorato EL, Schneider E, Van Camp G, Wuyts W, Smith RJ, Friderici KH. 2010. A novel DFNB1 deletion allele supports the existence of a distant cis-regulatory region that controls GJB2 and GJB6 expression. Clin Genet (in press).
341. Wilkins JM, Southam L, Mustafa Z, Chapman K, Loughlin J. 2009. Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis. BMC Med Genet 10:141.
342. Wong E, Wei CL. 2009. ChIP'ing the mammalian genome: technical advances and insights into functional elements. Genome Med 1:89.
343. Wright JB, Brown SJ, Cole MD. 2010. Upregulation of c-MYC in cis through a large chromatin loop linked to a cancer risk-associated single-nucleotide polymorphism in colorectal cancer cells. Mol Cell Biol 30:1411-1420.
344. Wu M, Jolicoeur N, Li Z, Zhang L, Fortin Y, L'Abbe D, Yu Z, Shen SH. 2008. Genetic variations of microRNAs in human cancer and their effects on the expression of miRNAs. Carcinogenesis 29:1710-1716.
345. Xing J, Zhang Y, Han K, Salem AH, Sen SK, Huff CD, Zhou Q, Kirkness EF, Levy S, Batzer MA, Jorde LB. 2009. Mobile elements create structural variation: analysis of a complete human genome. Genome Res 19:1516-1526.
346. Yagi M, Takeshima Y, Wada H, Nakamura H, Matsuo M. 2003. Two alternative exons can result from activation of the cryptic splice acceptor site deep within intron 2 of the dystrophin gene in a patient with as yet asymptomatic dystrophinopathy. Hum Genet 112:164-170. (Pubitemid 36869099)
347. Yamaguchi-Kabata Y, Shimada MK, Hayakawa Y, Minoshima S, Chakraborty R, Gojobori T, Imanishi T. 2008. Distribution and effects of nonsense polymorphisms in human genes. PLoS One 3:e3393.
348. Yang MQ, Elnitski LL. 2008. Diversity of core promoter elements comprising human bidirectional promoters. BMC Genomics 9(Suppl 2):S3.
349. Yang R, Frank B, Hemminki K, Bartram CR, Wappenschmidt B, Sutter C, Kiechle M, Bugert P, Schmutzler RK, Arnold N, Weber BH, Niederacher D, Meindl A, Burwinkel B. 2008a. SNPs in ultraconserved elements and familial breast cancer risk. Carcinogenesis 29:351-355. (Pubitemid 351359674)
350. Yang TL, Chen XD, Guo Y, Lei SF, Wang JT, Zhou Q, Pan F, Chen Y, Zhang ZX, Dong SS, Xu XH, Yan H, Liu X, Qiu C, Zhu XZ, Chen T, Li M, Zhang H, Zhang L, Drees BM, Hamilton JJ, Papasian CJ, Recker RR, Song XP, Cheng J, Deng HW. 2008b. Genome-wide copy-number-variation study identified a susceptibility gene, UGT2B17, for osteoporosis. Am J Hum Genet 83:663-674.
351. Yngvadottir B, MacArthur DG, Jin H, Tyler-Smith C. 2009a. The promise and reality of personal genomics. Genome Biol 10:237.
352. Yngvadottir B, Xue Y, Searle S, Hunt S, Delgado M, Morrison J, Whittaker P, Deloukas P, Tyler-Smith C. 2009b. A genome-wide survey of the prevalence and evolutionary forces acting on human nonsense SNPs. Am J Hum Genet 84:224-234.
353. Yu P, Ma D, Xu M. 2005. Nested genes in the human genome. Genomics 86:414-422.
354. Zhang C. 2008. MicroRNomics: a newly emerging approach for disease biology. Physiol. Genomics 33:139-147.
355. Zhang F, Carvalho CM, Lupski JR. 2009. Complex human chromosomal and genomic rearrangements. Trends Genet 25:298-307.
356. Zhang ZD, Frankish A, Hunt T, Harrow J, Gerstein M. 2010. Identification and analysis of unitary pseudogenes: historic and contemporary gene losses in humans and other primates. Genome Biol 11:R26.
357. Zhang ZD, Paccanaro A, Fu Y, Weissman S, Weng Z, Chang J, Snyder M, Gerstein MB. 2007. Statistical analysis of the genomic distribution and correlation of regulatory elements in the ENCODE regions. Genome Res 17:787-797.
358. Zheng D, Frankish A, Baertsch R, Kapranov P, Reymond A, Choo SW, Lu Y, Denoeud F, Antonarakis SE, Snyder M, Ruan Y, Wei CL, Gingeras TR, Guigó R, Harrow J, Gerstein MB. 2007. Pseudogenes in the ENCODE regions: consensus annotation, analysis of transcription, and evolution. Genome Res 17: 839-851.
359. Zheng D, Gerstein MB. 2007. The ambiguous boundary between genes and pseudogenes: the dead rise up, or do they? Trends Genet 23: 219-224.
360. Zhu QS, Xing W, Qian B, von Dippe P, Shneider BL, Fox VL, Levy D. 2003. Inhibition of human m-epoxide hydrolase gene expression in a case of hypercholanemia. Biochim Biophys Acta 1638:208-216.