Needles in stacks of needles: Finding disease-causal variants in a wealth of genomic data

Nature Reviews Genetics

Volumn 12, Issue 9, 2011, Pages 628-640

  Cooper, Gregory M ^a   Shendure, Jay ^b  

^a HUDSONALPHA INSTITUTE FOR BIOTECHNOLOGY   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CAUSAL ATTRIBUTION; FUNCTIONAL GENOMICS; GENE INTERACTION; GENE MUTATION; GENE SEQUENCE; GENETIC DISORDER; GENETIC VARIABILITY; HUMAN; HUMAN GENOME; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM;

AMINO ACID SEQUENCE; COMPUTATIONAL BIOLOGY; DATABASES, GENETIC; EVOLUTION, MOLECULAR; GENETIC ASSOCIATION STUDIES; GENETIC LINKAGE; GENETIC LOCI; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; GENOME, HUMAN; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; MOLECULAR SEQUENCE DATA; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEIN CONFORMATION; SEQUENCE ANALYSIS, DNA;

EID: 80051968181     PISSN: 14710056     EISSN: 14710064     Source Type: Journal    
DOI: 10.1038/nrg3046     Document Type: Review

References (117)

1. Shendure, J. & Ji, H. Next-generation DNA sequencing. Nature Biotech. 26, 1135-1145 (2008).
2. Bentley, D. R. et al. Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456, 53-59 (2008).
3. The 1000 Genomes Project Consortium. A map of human genome variation from population-scale sequencing. Nature 467, 1061-1073 (2010).
4. Lander, E. S. Initial impact of the sequencing of the human genome. Nature 470, 187-197 (2011).
5. Manly, K. F., Nettleton, D. & Hwang, J. T. Genomics, prior probability, and statistical tests of multiple hypotheses. Genome Res. 14, 997-1001 (2004). (Pubitemid 38811535)
6. Morton, N. E. Sequential tests for the detection of linkage. Am. J. Hum. Genet. 7, 277-318 (1955).
7. Ng, S. B. et al. Exome sequencing identifies the cause of a mendelian disorder. Nature Genet. 42, 30-35 (2010).
8. Ng, S. B. et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 461, 272-276 (2009).
9. Choi, M. et al. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc. Natl Acad. Sci. USA 106, 19096-19101 (2009).
10. Erlich, Y. et al. Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis. Genome Res. 21, 658-664 (2011).
11. Kimura, M. The Neutral Theory Of Molecular Evolution (Cambridge Univ. Press, New York, 1983).
12. Cooper, G. M. & Brown, C. D. Qualifying the relationship between sequence conservation and molecular function. Genome Res. 18, 201-205 (2008). (Pubitemid 351240729)
13. McAuliffe, J. D., Jordan, M. I. & Pachter, L. Subtree power analysis and species selection for comparative genomics. Proc. Natl Acad. Sci. USA 102, 7900-7905 (2005). (Pubitemid 40781035)
14. Stone, E. A., Cooper, G. M. & Sidow, A. Trade-offs in detecting evolutionarily constrained sequence by comparative genomics. Annu. Rev. Genomics Hum. Genet. 6, 143-164 (2005). (Pubitemid 41397079)
15. Eddy, S. R. A model of the statistical power of comparative genome sequence analysis. PLoS Biol. 3, e10 (2005).
16. The Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69-87 (2005).
17. Davydov, E. V. et al. Identifying a high fraction of the human genome to be under selective constraint using GERP++. PLoS Comput. Biol. 6, e1001025 (2010).
18. The Mouse Genome Sequencing Consortium. Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520-562 (2002).
19. The ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447, 799-816 (2007).
20. Boffelli, D. et al. Phylogenetic shadowing of primate sequences to find functional regions of the human genome. Science 299, 1391-1394 (2003). (Pubitemid 36254651)
21. Prabhakar, S. et al. Close sequence comparisons are sufficient to identify human cis-regulatory elements. Genome Res. 16, 855-863 (2006). (Pubitemid 43992909)
22. Kaessmann, H. Origins, evolution, and phenotypic impact of new genes. Genome Res. 20, 1313-1326 (2010).
23. Johnson, M. E. et al. Positive selection of a gene family during the emergence of humans and African apes. Nature 413, 514-519 (2001). (Pubitemid 32938748)
24. Wang, T. et al. Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53. Proc. Natl Acad. Sci. USA 104, 18613-18618 (2007). (Pubitemid 350210745)
25. Enard, W. et al. Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418, 869-872 (2002). (Pubitemid 34966304)
26. Prabhakar, S. et al. Human-specific gain of function in a developmental enhancer. Science 321, 1346-1350 (2008).
27. Stone, E. A. & Sidow, A. Physicochemical constraint violation by missense substitutions mediates impairment of protein function and disease severity. Genome Res. 15, 978-986 (2005). (Pubitemid 40994218)
28. De Gobbi, M. et al. A regulatory SNP causes a human genetic disease by creating a new transcriptional promoter. Science 312, 1215-1217 (2006). (Pubitemid 43801147)
29. Botstein, D. & Risch, N. Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease. Nature Genet. 33, 228-237 (2003). (Pubitemid 36278833)
30. Ng, S. B. et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nature Genet. 42, 790-793 (2010).
31. MacArthur, D. G. & Tyler-Smith, C. Loss-of-function variants in the genomes of healthy humans. Hum. Mol. Genet. 19, R125-R130 (2010).
32. Grantham, R. Amino acid difference formula to help explain protein evolution. Science 185, 862-864 (1974).
33. Ng, P. C. & Henikoff, S. Predicting the effects of amino acid substitutions on protein function. Annu. Rev. Genomics Hum. Genet. 7, 61-80 (2006). (Pubitemid 44627922)
34. Care, M. A., Needham, C. J., Bulpitt, A. J. & Westhead, D. R. Deleterious SNP prediction: be mindful of your training data! Bioinformatics 23, 664-672 (2007). (Pubitemid 46554716)
35. Adzhubei, I. A. et al. A method and server for predicting damaging missense mutations. Nature Methods 7, 248-249 (2010).
36. Bromberg, Y. & Rost, B. SNAP: predict effect of non-synonymous polymorphisms on function. Nucleic Acids Res. 35, 3823-3835 (2007). (Pubitemid 47244674)
37. Capriotti, E., Calabrese, R. & Casadio, R. Predicting the insurgence of human genetic diseases associated to single point protein mutations with support vector machines and evolutionary information. Bioinformatics 22, 2729-2734 (2006). (Pubitemid 44742391)
38. Ferrer-Costa, C., Orozco, M. & de la Cruz, X. Sequence-based prediction of pathological mutations. Proteins 57, 811-819 (2004). (Pubitemid 39627003)
39. Ng, P. C. & Henikoff, S. Predicting deleterious amino acid substitutions. Genome Res. 11, 863-874 (2001). (Pubitemid 32447869)
40. Schwarz, J. M., Rodelsperger, C., Schuelke, M. & Seelow, D. MutationTaster evaluates disease-causing potential of sequence alterations. Nature Methods 7, 575-576 (2010).
41. Thomas, P. D. et al. PANTHER: a library of protein families and subfamilies indexed by function. Genome Res. 13, 2129-2141 (2003). (Pubitemid 37161770)
42. Ye, Z. Q. et al. Finding new structural and sequence attributes to predict possible disease association of single amino acid polymorphism (SAP). Bioinformatics 23, 1444-1450 (2007).
43. Chun, S. & Fay, J. C. Identification of deleterious mutations within three human genomes. Genome Res. 19, 1553-1561 (2009).
44. Bao, L., Zhou, M. & Cui, Y. nsSNPAnalyzer: identifying disease-associated nonsynonymous single nucleotide polymorphisms. Nucleic Acids Res. 33, W480-W482 (2005). (Pubitemid 44529966)
45. Sunyaev, S. et al. Prediction of deleterious human alleles. Hum. Mol. Genet. 10, 591-597 (2001). (Pubitemid 32229363)
46. Ng, P. C. & Henikoff, S. SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res. 31, 3812-3814 (2003). (Pubitemid 37442253)
47. Lynch, M. & Conery, J. S. The evolutionary fate and consequences of duplicate genes. Science 290, 1151-1155 (2000).
48. Marini, N. J., Thomas, P. D. & Rine, J. The use of orthologous sequences to predict the impact of amino acid substitutions on protein function. PLoS Genet. 6, e1000968 (2010).
49. Dobson, R. J., Munroe, P. B., Caulfield, M. J. & Saqi, M. A. Predicting deleterious nsSNPs: an analysis of sequence and structural attributes. BMC Bioinformatics 7, 217 (2006).
50. Saunders, C. T. & Baker, D. Evaluation of structural and evolutionary contributions to deleterious mutation prediction. J. Mol. Biol. 322, 891-901 (2002).
51. Yue, P., Li, Z. & Moult, J. Loss of protein structure stability as a major causative factor in monogenic disease. J. Mol. Biol. 353, 459-473 (2005). (Pubitemid 41356624)
52. Bao, L. & Cui, Y. Prediction of the phenotypic effects of non-synonymous single nucleotide polymorphisms using structural and evolutionary information. Bioinformatics 21, 2185-2190 (2005). (Pubitemid 40731569)
53. Li, Y. et al. Predicting disease-associated substitution of a single amino acid by analyzing residue interactions. BMC Bioinformatics 12, 14 (2011).
54. Hindorff, L. A. et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl Acad. Sci. USA 106, 9362-9367 (2009).
55. Musunuru, K. et al. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 466, 714-719 (2010).
56. Storey, J. D. et al. Gene-expression variation within and among human populations. Am. J. Hum. Genet. 80, 502-509 (2007).
57. Nicolae, D. L. et al. Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS. PLoS Genet. 6, e1000888 (2010).
58. King, M. C. & Wilson, A. C. Evolution at two levels in humans and chimpanzees. Science 188, 107-116 (1975).
59. Carroll, S. B. Evolution at two levels: on genes and form. PLoS Biol. 3, e245 (2005).
60. Siepel, A. et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 15, 1034-1050 (2005). (Pubitemid 41126859)
61. Lettice, L. A. et al. 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 (2003). (Pubitemid 36896664)
62. Stenson, P. D. et al. The Human Gene Mutation Database: providing a comprehensive central mutation database for molecular diagnostics and personalized genomics. Hum. Genomics 4, 69-72 (2009).
63. Treisman, R., Orkin, S. H. & Maniatis, T. Specific transcription and RNA splicing defects in five cloned β-thalassaemia genes. Nature 302, 591-596 (1983). (Pubitemid 13118831)
64. Woolfe, A. et al. Highly conserved non-coding sequences are associated with vertebrate development. PLoS Biol. 3, e7 (2005).
65. Dehal, P. et al. The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins. Science 298, 2157-2167 (2002). (Pubitemid 35471235)
66. Pollard, K. S., Hubisz, M. J., Rosenbloom, K. R. & Siepel, A. Detection of nonneutral substitution rates on mammalian phylogenies. Genome Res. 20, 110-121 (2010).
67. Cooper, G. M. et al. Distribution and intensity of constraint in mammalian genomic sequence. Genome Res. 15, 901-913 (2005). (Pubitemid 40994210)
68. Asthana, S., Roytberg, M., Stamatoyannopoulos, J. & Sunyaev, S. Analysis of sequence conservation at nucleotide resolution. PLoS Comput. Biol. 3, e254 (2007).
69. Margulies, E. H., Blanchette, M., Haussler, D. & Green, E. D. Identification and characterization of multi-species conserved sequences. Genome Res. 13, 2507-2518 (2003). (Pubitemid 37541140)
70. Dubchak, I. et al. Active conservation of noncoding sequences revealed by three-way species comparisons. Genome Res. 10, 1304-1306 (2000).
71. Parker, S. C., Hansen, L., Abaan, H. O., Tullius, T. D. & Margulies, E. H. Local DNA topography correlates with functional noncoding regions of the human genome. Science 324, 389-392 (2009).
72. Cooper, G. M. et al. Single-nucleotide evolutionary constraint scores highlight disease-causing mutations. Nature Methods 7, 250-251 (2010).
73. Wang, G. S. & Cooper, T. A. Splicing in disease: disruption of the splicing code and the decoding machinery. Nature Rev. Genet. 8, 749-761 (2007). (Pubitemid 47429207)
74. Drake, J. A. et al. Conserved noncoding sequences are selectively constrained and not mutation cold spots. Nature Genet. 38, 223-227 (2006). (Pubitemid 43177238)
75. Katzman, S. et al. Human genome ultraconserved elements are ultraselected. Science 317, 915 (2007). (Pubitemid 47301312)
76. Goode, D. L. et al. Evolutionary constraint facilitates interpretation of genetic variation in resequenced human genomes. Genome Res. 20, 301-310 (2010).
77. Pennacchio, L. A. et al. In vivo enhancer analysis of human conserved non-coding sequences. Nature 444, 499-502 (2006). (Pubitemid 44809068)
78. Margulies, E. H. et al. Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome. Genome Res. 17, 760-774 (2007). (Pubitemid 46919712)
79. The ENCODE Project Consortium. A user's guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol. 9, e1001046 (2011).
80. Ge, B. et al. Global patterns of cis variation in human cells revealed by high-density allelic expression analysis. Nature Genet. 41, 1216-1222 (2009).
81. Nica, A. C. et al. Candidate causal regulatory effects by integration of expression QTLs with complex trait genetic associations. PLoS Genet. 6, e1000895 (2010).
82. Zheng, W., Zhao, H., Mancera, E., Steinmetz, L. M. & Snyder, M. Genetic analysis of variation in transcription factor binding in yeast. Nature 464, 1187-1191 (2010).
83. Patwardhan, R. P. et al. High-resolution analysis of DNA regulatory elements by synthetic saturation mutagenesis. Nature Biotech. 27, 1173-1175 (2009).
84. Pitt, J. N. & Ferre-D'Amare, A. R. Rapid construction of empirical RNA fitness landscapes. Science 330, 376-379 (2010).
85. Fowler, D. M. et al. High-resolution mapping of protein sequence-function relationships. Nature Methods 7, 741-746 (2010).
86. Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L. & Wold, B. Mapping and quantifying mammalian transcriptomes by RNA-seq. Nature Methods 5, 621-628 (2008). (Pubitemid 351911867)
87. Johnson, D. S., Mortazavi, A., Myers, R. M. & Wold, B. Genome-wide mapping of in vivo protein-DNA interactions. Science 316, 1497-1502 (2007). (Pubitemid 46906620)
88. Cao, A. R. et al. Genome-wide analysis of transcription factor E2F1 mutant proteins reveals that N-and C-terminal protein interaction domains do not participate in targeting E2F1 to the human genome. J. Biol. Chem. 286, 11985-11996 (2011).
89. Botstein, D. & Shortle, D. Strategies and applications of in vitro mutagenesis. Science 229, 1193-1201 (1985). (Pubitemid 15021669)
90. Blow, M. J. et al. ChIP-seq identification of weakly conserved heart enhancers. Nature Genet. 42, 806-810 (2010).
91. Cheng, Y. et al. Erythroid GATA1 function revealed by genome-wide analysis of transcription factor occupancy, histone modifications, and mRNA expression. Genome Res. 19, 2172-2184 (2009).
92. Miller, D. T. et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am. J. Hum. Genet. 86, 749-764 (2010).
93. Sebat, J. et al. Strong association of de novo copy number mutations with autism. Science 316, 445-449 (2007). (Pubitemid 46651493)
94. Walsh, T. et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320, 539-543 (2008). (Pubitemid 351590668)
95. Markiewicz, P., Kleina, L. G., Cruz, C., Ehret, S. & Miller, J. H. Genetic studies of the lac repressor. XIV. Analysis of 4000 altered Escherichia coli lac repressors reveals essential and non-essential residues, as well as "spacers" which do not require a specific sequence. J. Mol. Biol. 240, 421-433 (1994). (Pubitemid 24249917)
96. Rennell, D., Bouvier, S. E., Hardy, L. W. & Poteete, A. R. Systematic mutation of bacteriophage T4 lysozyme. J. Mol. Biol. 222, 67-88 (1991). (Pubitemid 121003989)
97. Loeb, D. D. et al. Complete mutagenesis of the HIV-1 protease. Nature 340, 397-400 (1989). (Pubitemid 19191607)
98. Hardison, R. C. et al. HbVar: a relational database of human hemoglobin variants and thalassemia mutations at the globin gene server. Hum. Mutat. 19, 225-233 (2002). (Pubitemid 34195183)
99. Olivier, M. et al. The IARC TP53 database: new online mutation analysis and recommendations to users. Hum. Mutat. 19, 607-614 (2002). (Pubitemid 34556481)
100. Yip, Y. L. et al. The Swiss-Prot variant page and the ModSNP database: a resource for sequence and structure information on human protein variants. Hum. Mutat. 23, 464-470 (2004). (Pubitemid 38569219)
101. Brown, C. D., Johnson, D. S. & Sidow, A. Functional architecture and evolution of transcriptional elements that drive gene coexpression. Science 317, 1557-1560 (2007). (Pubitemid 47417436)
102. Kim, J., He, X. & Sinha, S. Evolution of regulatory sequences in 12 Drosophila species. PLoS Genet. 5, e1000330 (2009).
103. Moses, A. M., Chiang, D. Y., Kellis, M., Lander, E. S. & Eisen, M. B. Position specific variation in the rate of evolution in transcription factor binding sites. BMC Evol. Biol. 3, 19 (2003).
104. Visel, A. et al. ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature 457, 854-858 (2009).
105. Dekker, J., Rippe, K., Dekker, M. & Kleckner, N. Capturing chromosome conformation. Science 295, 1306-1311 (2002). (Pubitemid 34157624)
106. Liu, D. J. & Leal, S. M. A novel adaptive method for the analysis of next-generation sequencing data to detect complex trait associations with rare variants due to gene main effects and interactions. PLoS Genet. 6, e1001156 (2010).
107. Yandell, M. et al. A probabilistic disease-gene finder for personal genomes. Genome Res. 23 Jun 2011(doi:10.1101/gr.123158.111).
108. Gerke, J., Lorenz, K. & Cohen, B. Genetic interactions between transcription factors cause natural variation in yeast. Science 323, 498-501 (2009).
109. Gerke, J., Lorenz, K., Ramnarine, S. & Cohen, B. Gene-environment interactions at nucleotide resolution. PLoS Genet. 6, e1001144 (2010).
110. Bush, W. S. et al. A knowledge-driven interaction analysis reveals potential neurodegenerative mechanism of multiple sclerosis susceptibility. Genes Immun. (2011).
111. Rual, J. F. et al. Towards a proteome-scale map of the human protein-protein interaction network. Nature 437, 1173-1178 (2005).
112. Emilsson, V. et al. Genetics of gene expression and its effect on disease. Nature 452, 423-428 (2008). (Pubitemid 351450845)
113. The Gene Ontology Consortium. et al. Gene ontology: tool for the unification of biology. Nature Genet. 25, 25-29 (2000).
114. Risch, N. & Merikangas, K. The future of genetic studies of complex human diseases. Science 273, 1516-1517 (1996). (Pubitemid 26301653)
115. Ioannidis, J. P. Why most published research findings are false. PLoS Med. 2, e124 (2005).
116. Rothman, K. J. No adjustments are needed for multiple comparisons. Epidemiology 1, 43-46 (1990). (Pubitemid 20255621)
117. Keinan, A., Mullikin, J. C., Patterson, N. & Reich, D. Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans. Nature Genet. 39, 1251-1255 (2007) (Pubitemid 47482683)