Inferring causality and functional significance of human coding dna variants

Human Molecular Genetics

Volumn 21, Issue R1, 2012, Pages

  Sunyaev, Shamil R ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; DNA;

AMINO ACID SUBSTITUTION; ARTICLE; GENE FREQUENCY; GENE FUNCTION; GENETIC ANALYSIS; GENETIC CODE; GENETIC VARIABILITY; HUMAN; IN VITRO STUDY; MISSENSE MUTATION; PHENOTYPE; PREDICTION; PRIORITY JOURNAL;

ALLELES; AMINO ACID SUBSTITUTION; DNA; EXOME; GENE FREQUENCY; GENETIC PREDISPOSITION TO DISEASE; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; HUMANS; MUTATION, MISSENSE; PHENOTYPE; SEQUENCE ANALYSIS, DNA;

EID: 84867113601     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/dds385     Document Type: Article

References (78)

1. [1000] Genomes Project Consortium (2010) A map of human genome variation from population-scale sequencing. Nature, 467, 1061-1073.
2. Tennessen, J.A., Bigham, A.W., ÓConnor, T.D., Fu, W., Kenny, E.E., Gravel, S., McGee, S., Do, R., Liu, X. and Jun, G. (2012) Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science, 337, 64-69.
3. Plon, S.E., Eccles, D.M. and Easton, D. and IARC Unclassified Genetic Variants Working Group (2008) Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results. Hum. Mutat., 29, 1282-1291.
4. Ng, S.B., Buckingham, K.J., Lee, C., Bigham, A.W., Tabor, H.K., Dent, K.M., Huff, C.D., Shannon, P.T., Jabs, E.W., Nickerson, D.A. et al. (2010) Exome sequencing identifies the cause of a Mendelian disorder. Nat. Genet., 42, 30-35.
5. Roach, J.C., Glusman, G., Smit, A.F., Huff, C.D., Hubley, R., Shannon, P.T., Rowen, L., Pant, K.P., Goodman, N., Bamshad, M. et al. (2010) Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science, 328, 636-639.
6. Neale, B.M., Kou, Y., Liu, L., Máayan, A., Samocha, K.E., Sabo, A., Lin, C.F., Stevens, C., Wang, L.S., Makarov, V. et al. (2012) Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature, 485, 242-245.
7. óRoak, B.J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B.P., Levy, R., Ko, A., Lee, C., Smith, J.D. et al. (2012) Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature, 485, 246-250.
8. Sanders, S.J., Murtha, M.T., Gupta, A.R., Murdoch, J.D., Raubeson, M.J., Willsey, A.J., Ercan-Sencicek, A.G., DiLullo, N.M., Parikshak, N.N., Stein, J.L. et al. (2012) De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature, 485, 237-241.
9. Xu, B., Roos, J.L., Dexheimer, P., Boone, B., Plummer, B., Levy, S., Gogos, J.A. and Karayiorgou, M. (2011) Exome sequencing supports a de novo mutational paradigm for schizophrenia. Nat. Genet., 43, 864-868.
10. Kondrashov, A.S. (2003) Direct estimates of human per nucleotide mutation rates at 20 loci causing Mendelian diseases. Hum. Mutat., 21, 12-27.
11. Nachman, M.W. and Crowell, S.L. (2000) Estimate of the mutation rate per nucleotide in humans. Genetics, 156, 297-304.
12. Kong, A., Frigge, M.L., Masson, G., Besenbacher, S., Sulem, P., Magnusson, G., Gudjonsson, S.A., Sigurdsson, A., Jonasdottir, A., Jonasdottir, A. et al. (2012) Rate of de novo mutations and the importance of fatheŕs age to disease risk. Nature, 488, 471-475.
13. Sun, J.X., Helgason, A., Masson, G., Ebenesersdò ttir, S.S., Li, H., Mallick, S., Gnerre, S., Patterson, N., Kong, A., Reich, D. and Stefansson, K. (2012) A direct characterization of human mutation based on microsatellites. Nat. Genet. doi, 10.1038/ng.2398
14. Dickson, S.P., Wang, K., Krantz, I., Hakonarson, H. and Goldstein, D.B. (2010) Rare variants create synthetic genome-wide associations. PLoS Biol., 8, e1000294.
15. Wray, N.R., Purcell, S.M. and Visscher, P.M. (2011) Synthetic associations created by rare variants do not explain most GWAS results. PLoS Biol., 9, e1000579.
16. Musunuru, K., Strong, A., Frank-Kamenetsky, M., Lee, N.E., Ahfeldt, T., Sachs, K.V., Li, X., Li, H., Kuperwasser, N., Ruda, V.M. et al. (2010) From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature, 466, 714-719.
17. Raychaudhuri, S., Sandor, C., Stahl, E.A., Freudenberg, J., Lee, H.S., Jia, X., Alfredsson, L., Padyukov, L., Klareskog, L., Worthington, J. et al. (2012) Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat. Genet., 44, 291-296.
18. International HIV Controllers StudyPereyra, F., Jia, X., McLaren, P.J., Telenti, A., de Bakker, P.I., Walker, B.D., Ripke, S., Brumme, C.J., Pulit, S.L. et al. (2010) The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science, 330, 1551-1557.
19. Stranger, B.E., Nica, A.C., Forrest, M.S., Dimas, A., Bird, C.P., Beazley, C., Ingle, C.E., Dunning, M., Flicek, P., Koller, D. et al. (2007) Population genomics of human gene expression. Nat. Genet., 39, 1217-1224.
20. McDaniell, R., Lee, B.K., Song, L., Liu, Z., Boyle, A.P., Erdos, M.R., Scott, L.J., Morken, M.A., Kucera, K.S., Battenhouse, A. et al. (2010) Heritable individual-specific and allele-specific chromatin signatures in humans. Science, 328, 235-239.
21. Degner, J.F., Pai, A.A., Pique-Regi, R., Veyrieras, J.B., Gaffney, D.J., Pickrell, J.K., De Leon, S., Michelini, K., Lewellen, N., Crawford, G.E. et al. (2012) DNase I sensitivity QTLs are a major determinant of human expression variation. Nature, 482, 390-394.
22. Maurano, M.T., Humbert, R., Rynes, E., Thurman, R.E., Haugen, E., Wang, H., Reynolds, A.P., Sandstrom, R., Qu, H. and Brody, J. (2012) Systematic localization of common disease-associated variation in regulatory DNA. Science, 337, 1190-1195.
23. Cohen, J.C., Kiss, R.S., Pertsemlidis, A., Marcel, Y.L., McPherson, R. and Hobbs, H.H. (2004) Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science, 305, 869-872.
24. Romeo, S., Yin, W., Kozlitina, J., Pennacchio, L.A., Boerwinkle, E., Hobbs, H.H. and Cohen, J.C. (2009) Rare loss-of-function mutations inANGPTL family members contribute to plasma triglyceride levels in humans. J. Clin. Invest., 119, 70-79.
25. Ji, W., Foo, J.N., óRoak, B.J., Zhao, H., Larson, M.G., Simon, D.B., Newton-Cheh, C., State, M.W., Levy, D. and Lifton, R.P. (2008) Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat. Genet., 40, 592-599.
26. Johansen, C.T., Wang, J., Lanktree, M.B., McIntyre, A.D., Ban, M.R., Martins, R.A., Kennedy, B.A., Hassell, R.G., Visser, M.E., Schwartz, S.M. et al. (2010) Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia. Nat. Genet., 42, 684-687.
27. Ahituv, N., Kavaslar, N., Schackwitz, W., Ustaszewska, A., Martin, J., Hebert, S., Doelle, H., Ersoy, B., Kryukov, G., Schmidt, S. et al. (2007) Medical sequencing at the extremes of human body mass. Am. J. Hum. Genet., 80, 779-791.
28. Rivas, M.A., Beaudoin, M., Gardet, A., Stevens, C., Sharma, Y., Zhang, C.K., Boucher, G., Ripke, S., Ellinghaus, D., Burtt, N., Fennell, T. et al. (2011) Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat. Genet., 43, 1066-1073.
29. Jordan, C.T., Cao, L., Roberson, E.D., Duan, S., Helms, C.A., Nair, R.P., Duffin, K.C., Stuart, P.E., Goldgar, D., Hayashi, G. et al. (2012) Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis. Am. J. Hum. Genet., 90, 796-808.
30. Bonnefond, A., Clément, N., Fawcett, K., Yengo, L., Vaillant, E., Guillaume, J.L., Dechaume, A., Payne, F., Roussel, R., Czernichow, S. et al. (2012) Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nat. Genet., 44, 297-301.
31. Momozawa, Y., Mni, M., Nakamura, K., Coppieters, W., Almer, S., Amininejad, L., Cleynen, I., Colombel, J.F., de Rijk, P., Dewit, O. et al. (2011) Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease. Nat. Genet., 43, 43-47.
32. Kiezun, A., Garimella, K., Do, R., Stitziel, N.O., Neale, B.M., McLaren, P.J., Gupta, N., Sklar, P., Sullivan, P.F. and Moran, J.L. (2012) Exome sequencing and the genetic basis of complex traits. Nat. Genet., 44, 623- 630.
33. Price, A.L., Kryukov, G.V., de Bakker, P.I., Purcell, S.M., Staples, J., Wei, L.J. and Sunyaev, S.R. (2010) Pooled association tests for rare variants in exon-resequencing studies. Am. J. Hum. Genet., 86, 832-838.
34. MacArthur, D.G., Balasubramanian, S., Frankish, A., Huang, N., Morris, J., Walter, K., Jostins, L., Habegger, L., Pickrell, J.K., Montgomery, S.B. et al. (2012) A systematic survey of loss-of-function variants in human protein-coding genes. Science, 335, 823-828.
35. Wang, X., Grus, W.E. and Zhang, J. (2006) Gene losses during human origins. PLoS Biol., 4, e52.
36. Jordan, D.M., Kiezun, A., Baxter, S.M., Agarwala, V., Green, R.C., Murray, M.F., Pugh, T., Lebo, M.S., Rehm, H.L., Funke, B.H. and Sunyaev, S.R. (2011) Development and validation of a computational method for assessment of missense variants in hypertrophic cardiomyopathy. Am. J. Hum. Genet., 88, 183-192.
37. Mitchell, A.A., Chakravarti, A. and Cutler, D.J. (2005) On the probability that a novel variant is a disease-causing mutation. Genome Res., 15, 960- 966.
38. Marth, G.T., Czabarka, E., Murvai, J. and Sherry, S.T. (2004) The allele frequency spectrum in genome-wide human variation data reveals signals of differential demographic history in three large world populations. Genetics, 166, 351-372.
39. Williamson, S.H., Hernandez, R., Feldel-Alon, A., Zhe, L., Nielsen, R. and Bustamante, C.D. (2005) Simultaneous inference of selection and population growth from patterns of variation in the human genome. Proc. Natl Acad. Sci. USA, 102, 7882-7887.
40. Kryukov, G.V., Shpunt, A., Stamatoyannopoulos, J.A. and Sunyaev, S.R. (2009) Power of deep, all-exon resequencing for discovery of human trait genes. Proc. Natl Acad. Sci. USA, 106, 3871-3876.
41. Sunyaev, S.R., Lathe, W.C. III, Ramensky, V.E. and Bork, P. (2000) SNP frequencies in human genes an excess of rare alleles and differing modes of selection. Trends Genet., 16, 335-337.
42. Kryukov, G.V., Pennacchio, L.A. and Sunyaev, S.R. (2007) Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. Am. J. Hum. Genet., 80, 727-739.
43. Boyko, A.R., Williamson, S.H., Indap, A.R., Degenhardt, J.D., Hernandez, R.D., Lohmueller, K.E., Adams, M.D., Schmidt, S., Sninsky, J.J., Sunyaev, S.R. et al. (2008) Assessing the evolutionary impact of amino acid mutations in the human genome. PLoS Genet., 4, e1000083.
44. Li, Y., Vinckenbosch, N., Tian, G., Huerta-Sanchez, E., Jiang, T., Jiang, H., Albrechtsen, A., Andersen, G., Cao, H., Korneliussen, T. et al. (2010) Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants. Nat. Genet., 42, 969-972.
45. Rivière, J.B., van Bon, B.W., Hoischen, A., Kholmanskikh, S.S., ÓRoak, B.J., Gilissen, C., Gijsen, S., Sullivan, C.T., Christian, S.L., Abdul-Rahman, O.A. et al. (2012) De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. Nat. Genet., 44, 440-444.
46. Le Goff, C., Mahaut, C., Abhyankar, A., Le Goff, W., Serre, V., Afenjar, A., Destrée, A., di Rocco, M., Héron, D., Jacquemont, S. et al. (2011) Mutations at a single codon in Mad homology 2 domain of SMAD4 cause Myhre syndrome. Nat. Genet., 44, 85-88.
47. Van Houdt, J.K., Nowakowska, B.A., Sousa, S.B., van Schaik, B.D., Seuntjens, E., Avonce, N., Sifrim, A., Abdul-Rahman, O.A., van den Boogaard, M.J., Bottani, A. et al. (2012) Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome. Nat. Genet., 44, 445-449.
48. Heinzen, E.L., Swoboda, K.J., Hitomi, Y., Gurrieri, F., Nicole, S., de Vries, B., Tiziano, F.D., Fontaine, B., Walley, N.M., Heavin, S. et al. (2012) De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. Nat. Genet., 44, 1030-1034.
49. Rivière, J.B., Mirzaa, G.M., ÓRoak, B.J., Beddaoui, M., Alcantara, D., Conway, R.L., St-Onge, J., Schwartzentruber, J.A., Gripp, K.W., Nikkel, S.M. et al. (2012) De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat. Genet., 44, 934-940.
50. Boileau, C., Guo, D.C., Hanna, N., Regalado, E.S., Detaint, D., Gong, L., Varret, M., Prakash, S.K., Li, A.H., d'Indy, H. et al. (2012) TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome. Nat. Genet., 44, 916-921.
51. Wortmann, S.B., Vaz, F.M., Gardeitchik, T., Vissers, L.E., Renkema, G.H., Schuurs-Hoeijmakers, J.H., Kulik, W., Lammens, M., Christin, C., Kluijtmans, L.A. et al. (2012) Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness. Nat. Genet., 44, 797-802.
52. Rademakers, R., Baker, M., Nicholson, A.M., Rutherford, N.J., Finch, N., Soto-Ortolaza, A., Lash, J., Wider, C., Wojtas, A., DeJesus-Hernandez, M. et al. (2011) Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nat. Genet., 44, 200-205.
53. Sarparanta, J., Jonson, P.H., Golzio, C., Sandell, S., Luque, H., Screen, M., McDonald, K., Stajich, J.M., Mahjneh, I., Vihola, A. et al. (2012) Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy. Nat. Genet., 44, 450- 455.
54. Grall, A., Guaguère, E., Planchais, S., Grond, S., Bourrat, E., Hausser, I., Hitte, C., Le Gallo, M., Derbois, C., Kim, G.J. et al. (2012) PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever 4s and humans. Nat. Genet., 44, 140-147.
55. Louis-Dit-Picard, H., Barc, J., Trujillano, D., Miserey-Lenkei, S., Bouatia-Naji, N., Pylypenko, O., Beaurain, G., Bonnefond, A., Sand, O., Simian, C. et al. (2012) KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. Nat. Genet., 44, 456-460.
56. Wan, J., Yourshaw, M., Mamsa, H., Rudnik-Schöneborn, S., Menezes, M.P., Hong, J.E., Leong, D.W., Senderek, J., Salman, M.S., Chitayat, D. et al. (2012) Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration. Nat. Genet., 44, 704-708.
57. Zaghloul, N.A. and Katsanis, N. (2011) Zebrafish assays of ciliopathies. Methods Cell Biol., 105, 257-272.
58. Mayfield, J.A., Davies, M.W., Dimster-Denk, D., Pleskac, N., McCarthy, S., Boydston, E.A., Fink, L., Lin, X.X., Narain, A.S., Meighan, M. and Rine, J. (2012) Surrogate genetics and metabolic profiling for characterization of human disease alleles. Genetics, 190, 1309-1323.
59. Hicks, S., Wheeler, D.A., Plon, S.E. and Kimmel, M. (2011) Prediction of missense mutation functionality depends on both the algorithm and sequence alignment employed. Hum. Mutat., 32, 661-668.60.
60. Jordan, D.M., Ramensky, V.E. and Sunyaev, S.R. (2010) Human allelic variation: perspective from protein function, structure, and evolution. Curr. Opin. Struct. Biol., 20, 342-350.
61. Richards, C.S., Bale, S., Bellissimo, D.B., Das, S., Grody, W.W., Hegde, M.R., Lyon, E. and Ward, B.E. and Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee. (2008) ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007. Genet. Med., 10, 294-300.
62. Ng, P.C. and Henikoff, S. (2001) Predicting deleterious amino acid substitutions. Genome Res., 11, 863-874.
63. Sunyaev, S.R., Ramensky, V.E., Koch, I., Lathe, W. III, Kondrashov, A.S. and Bork, P. (2001) Prediction of deleterious human alleles. Hum. Mol. Genet., 15, 591-597.
64. Chasman, D. and Adams, R.M. (2001) Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation. J. Mol. Biol., 307, 683-706.
65. Yue, P., Li, Z. and Moult, J. (2005) Loss of protein structure stability as a major causative factor in monogenic disease. J. Mol. Biol., 353, 459-473.
66. Potapov, V., Cohen, M. and Schreiber, G. (2009) Assessing computational methods for predicting protein stability upon mutation: good on average but not in the details. Protein Eng. Des. Sel., 22, 553-560.
67. Adzhubei, I.A., Schmidt, S., Peshkin, L., Ramensky, V.E., Gerasimova, A., Bork, P., Kondrashov, A.S. and Sunyaev, S.R. (2010) A method and server for predicting damaging missense mutations. Nat. Methods, 7, 248-249.
68. Kumar, S., Suleski, M.P., Markov, G.J., Lawrence, S., Marco, A. and Filipski, A.J. (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.
69. Stone, E.A. and Sidow, A. (2005) Physicochemical constraint violation by missense substitutions mediates impairment of protein function and disease severity. Genome Res., 15, 978-986.
70. Chun, S. and Fay, J.C. (2009) Identification of deleterious mutations within three human genomes. Genome Res., 19, 1553-1561.
71. Cooper, G.M., Goode, D.L., Ng, S.B., Sidow, A., Bamshad, M.J., Shendure, J. and Nickerson, D.A. (2010) Single-nucleotide evolutionary constraint scores highlight disease-causing mutations. Nat. Methods, 7, 250-251.
72. Schwarz, J.M., Rödelsperger, C., Schuelke, M. and Seelow, D. (2010) MutationTaster evaluates disease-causing potential of sequence alterations. Nat. Methods, 7, 575-576.
73. Bromberg, Y., Yachdav, G. and Rost, B. (2008) SNAP predicts effect of mutations on protein function. Bioinformatics, 24, 2397-2398.
74. González-Pérez, A. and López-Bigas, N. (2011) Improving the assessment of the outcome of nonsynonymous SNVs with a consensus deleteriousness score, Condel. Am. J. Hum. Genet., 88, 440-449.
75. Karchin, R., Monteiro, A.N., Tavtigian, S.V., Carvalho, M.A. and Sali, A. (2007) Functional impact of missense variants in BRCA1 predicted by supervised learning. PLoS Comput. Biol., 3, e26.
76. Kondrashov, A.S., Sunyaev, S. and Kondrashov, F.A. (2002) Dobzhansky-Muller incompatibilities in protein evolution. Proc. Natl Acad. Sci. USA, 99, 14878-14883.
77. Do, R., Kathiresan, S. and Abecasis, G. Exome sequencing and complex disease: practical aspects of rare variant association studies. Hum. Mol. Genet. (in press).
78. Livingston, R.J., von Niederhausern, A., Jegga, A.G., Crawford, D.C., Carlson, C.S., Rieder, M.J., Gowrisankar, S., Aronow, B.J., Weiss, R.B. and Nickerson, D.A. (2004) Pattern of sequence variation across 213 environmental response genes. Genome Res., 14, 1821-1831.