A method for calculating probabilities of fitness consequences for point mutations across the human genome

Nature Genetics

Volumn 47, Issue 3, 2015, Pages 276-283

  Gulko, Brad ^a   Hubisz, Melissa J ^b   Gronau, Ilan ^b   Siepel, Adam ^a,b  

^a Department of Computer Science and School of Operations Research and Information Engineering   (United States)

^b Plant Breeding and Genetics Section in the School of Integrative Plant Science   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NUCLEOTIDE;

ARTICLE; CHIMPANZEE; CIS REGULATORY ELEMENT; EMBRYO; EVOLUTION; FITNESS CONSEQUENCE; FUNCTIONAL GENOMICS; GENETIC ASSOCIATION; GENETIC CONSERVATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GENOME ANALYSIS; HIGH THROUGHPUT SEQUENCING; HUMAN; HUMAN CELL; HUMAN GENOME; NATURAL SELECTION; NONHUMAN; NUCLEOTIDE SEQUENCE; POINT MUTATION; PREDICTION; PRIORITY JOURNAL; PROBABILITY; REGULATORY SEQUENCE; ANIMAL; CELL LINE; GENETICS; MOLECULAR EVOLUTION; PAN TROGLODYTES; REPRODUCTIVE FITNESS; UMBILICAL VEIN ENDOTHELIAL CELL;

PAN;

ANIMALS; CELL LINE; EVOLUTION, MOLECULAR; GENETIC FITNESS; GENOME, HUMAN; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; PAN TROGLODYTES; POINT MUTATION; POLYMORPHISM, GENETIC; PROBABILITY; REGULATORY SEQUENCES, NUCLEIC ACID;

EID: 84924039302     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.3196     Document Type: Article

References (54)

1. Mardis, E.R. A decade's perspective on DNA sequencing technology. Nature 470, 198-203 (2011).
2. Wold, B. & Myers, R.M. Sequence census methods for functional genomics. Nat. Methods 5, 19-21 (2008).
3. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57-74 (2012).
4. Shen, Y. et al. A map of the cis-regulatory sequences in the mouse genome. Nature 488, 116-120 (2012).
5. Neph, S. et al. An expansive human regulatory lexicon encoded in transcription factor footprints. Nature 489, 83-90 (2012).
6. Lappalainen, T. et al. Transcriptome and genome sequencing uncovers functional variation in humans. Nature 501, 506-511 (2013).
7. Cooper, G.M. & Shendure, J. Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data. Nat. Rev. Genet. 12, 628-640 (2011).
8. Mayor, C. et al. VISTA: visualizing global DNA sequence alignments of arbitrary length. Bioinformatics 16, 1046-1047 (2000).
9. Margulies, E.H., Blanchette, M., Program, N.C.S., Haussler, D. & Green, E.D. Identification and characterization of multi-species conserved sequences. Genome Res. 13, 2507-2518 (2003).
10. Boffelli, D. et al. Phylogenetic shadowing of primate sequences to find functional regions of the human genome. Science 299, 1391-1394 (2003).
11. Ovcharenko, I., Boffelli, D. & Loots, G.G. eShadow: a tool for comparing closely related sequences. Genome Res. 14, 1191-1198 (2004).
12. Siepel, A. et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 15, 1034-1050 (2005).
13. Cooper, G.M. et al. Distribution and intensity of constraint in mammalian genomic sequence. Genome Res. 15, 901-913 (2005).
14. Asthana, S., Roytberg, M., Stamatoyannopoulos, J. & Sunyaev, S. Analysis of sequence conservation at nucleotide resolution. PLOS Comput. Biol. 3, e254 (2007).
15. 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).
16. Graur, D. et al. On the immortality of television sets: "function" in the human genome according to the evolution-free gospel of ENCODE. Genome Biol. Evol. 5, 578-590 (2013).
17. Niu, D.K. & Jiang, L. Can ENCODE tell us how much junk DNA we carry in our genome? Biochem. Biophys. Res. Commun. 430, 1340-1343 (2013).
18. Doolittle, W.F. Is junk DNA bunk? A critique of ENCODE. Proc. Natl. Acad. Sci. USA 110, 5294-5300 (2013).
19. Eddy, S.R. The ENCODE project: missteps overshadowing a success. Curr. Biol. 23, R259-R261 (2013).
20. McDonald, J.H. & Kreitman, M. Adaptive protein evolution at the Adh locus in Drosophila. Nature 351, 652-654 (1991).
21. Fay, J.C., Wyckoff, G.J. & Wu, C.I. Positive and negative selection on the human genome. Genetics 158, 1227-1234 (2001).
22. Andolfatto, P. Adaptive evolution of non-coding DNA in Drosophila. Nature 437, 1149-1152 (2005).
23. Eyre-Walker, A., Woolfit, M. & Phelps, T. The distribution of fitness effects of new deleterious amino acid mutations in humans. Genetics 173, 891-900 (2006).
24. Boyko, A.R. et al. Assessing the evolutionary impact of amino acid mutations in the human genome. PLoS Genet. 4, e1000083 (2008).
25. Wilson, D.J., Hernandez, R.D., Andolfatto, P. & Przeworski, M. A population genetics-phylogenetics approach to inferring natural selection in coding sequences. PLoS Genet. 7, e1002395 (2011).
26. Ward, L.D. & Kellis, M. Evidence of abundant purifying selection in humans for recently acquired regulatory functions. Science 337, 1675-1678 (2012).
27. Khurana, E. et al. Integrative annotation of variants from 1092 humans: application to cancer genomics. Science 342, 1235587 (2013).
28. Arbiza, L. et al. Genome-wide inference of natural selection on human transcription factor binding sites. Nat. Genet. 45, 723-729 (2013).
29. Narlikar, L. et al. Genome-wide discovery of human heart enhancers. Genome Res. 20, 381-392 (2010).
30. Ritchie, G.R., Dunham, I., Zeggini, E. & Flicek, P. Functional annotation of noncoding sequence variants. Nat. Methods 11, 294-296 (2014).
31. Ernst, J. & Kellis, M. Discovery and characterization of chromatin states for systematic annotation of the human genome. Nat. Biotechnol. 28, 817-825 (2010).
32. Hoffman, M.M. et al. Unsupervised pattern discovery in human chromatin structure through genomic segmentation. Nat. Methods 9, 473-476 (2012).
33. Hoffman, M.M. et al. Integrative annotation of chromatin elements from ENCODE data. Nucleic Acids Res. 41, 827-841 (2013).
34. Gronau, I., Arbiza, L., Mohammed, J. & Siepel, A. Inference of natural selection from interspersed genomic elements based on polymorphism and divergence. Mol. Biol. Evol. 30, 1159-1171 (2013).
35. Kircher, M. et al. A general framework for estimating the relative pathogenicity of human genetic variants. Nat. Genet. 46, 310-315 (2014).
36. Boyle, A.P. et al. Annotation of functional variation in personal genomes using Regulome DB. Genome Res. 22, 1790-1797 (2012).
37. Erwin, G.D. et al. Integrating diverse datasets improves developmental enhancer prediction. PLOS Comput. Biol. 10, e1003677 (2014).
38. Gerstein, M.B. et al. Architecture of the human regulatory network derived from ENCODE data. Nature 489, 91-100 (2012).
39. Core, L.J. et al. Analysis of nascent RNA identifies a unified architecture of transcription initiation regions at mammalian promoters and enhancers. Nat. Genet. 46, 1311-1320 (2014).
40. Mouse Genome Sequencing Consortium. Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520-562 (2002).
41. Cooper, G.M. et al. Characterization of evolutionary rates and constraints in three mammalian genomes. Genome Res. 14, 539-548 (2004).
42. Lindblad-Toh, K. et al. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 438, 803-819 (2005).
43. Lindblad-Toh, K. et al. A high-resolution map of human evolutionary constraint using 29 mammals. Nature 478, 476-482 (2011).
44. Ponting, C.P., Nellaker, C. & Meader, S. Rapid turnover of functional sequence in human and other genomes. Annu. Rev. Genomics Hum. Genet. 12, 275-299 (2011).
45. Chiaromonte, F. et al. The share of human genomic DNA under selection estimated from human-mouse genomic alignments. Cold Spring Harb. Symp. Quant. Biol. 68, 245-254 (2003).
46. Meader, S., Ponting, C.P. & Lunter, G. Massive turnover of functional sequence in human and other mammalian genomes. Genome Res. 20, 1335-1343 (2010).
47. Smith, N.G., Brandstrom, M. & Ellegren, H. Evidence for turnover of functional noncoding DNA in mammalian genome evolution. Genomics 84, 806-813 (2004).
48. Ponting, C.P. & Hardison, R.C. What fraction of the human genome is functional? Genome Res. 21, 1769-1776 (2011).
49. Rands, C.M., Meader, S., Ponting, C.P. & Lunter, G. 8.2% of the human genome is constrained: variation in rates of turnover across functional element classes in the human lineage. PLoS Genet. 10, e1004525 (2014).
50. Lunter, G., Ponting, C.P. & Hein, J. Genome-wide identification of human functional DNA using a neutral indel model. PLOS Comput. Biol. 2, e5 (2006).
51. Kellis, M. et al. Defining functional DNA elements in the human genome. Proc. Natl. Acad. Sci. USA 111, 6131-6138 (2014).
52. Pheasant, M. & Mattick, J.S. Raising the estimate of functional human sequences. Genome Res. 17, 1245-1253 (2007).
53. Gronau, I., Hubisz, M.J., Gulko, B., Danko, C.G. & Siepel, A. Bayesian inference of ancient human demography from individual genome sequences. Nat. Genet. 43, 1031-1034 (2011).
54. Harrow, J. et al. GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 22, 1760-1774 (2012).