Genomic Patterns of De Novo Mutation in Simplex Autism

Cell

Volumn 171, Issue 3, 2017, Pages 710-722.e12

  Turner, Tychele N ^a   Coe, Bradley P ^a   Dickel, Diane E ^b   Hoekzema, Kendra ^a   Nelson, Bradley J ^a   Zody, Michael C ^c   Kronenberg, Zev N ^a   Hormozdiari, Fereydoun ^d   Raja, Archana ^a,e   Pennacchio, Len A ^b,f   Darnell, Robert B ^c,g   Eichler, Evan E ^a,e  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^b LAWRENCE BERKELEY NATIONAL LABORATORY   (United States)

^c NEW YORK GENOME CENTER   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e UNIVERSITY OF WASHINGTON   (United States)

^f DOE JOINT GENOME INSTITUTE   (United States)

^g ROCKEFELLER UNIVERSITY   (United States)

Author keywords

attributable fraction; autism; de novo mutation; genome sequencing; mechanisms of disease; multifactorial genetics; noncoding; oligogenic; regulatory

Indexed keywords

REPETITIVE DNA;

ARTICLE; AUTISM; COPY NUMBER VARIATION; DE NOVO MUTATION; EMBRYONIC STEM CELL; ENHANCER REGION; FETUS BRAIN; GENE MAPPING; GENE MUTATION; GENETIC ASSOCIATION; GENOMICS; IDIOPATHIC DISEASE; MISSENSE MUTATION; MUTATION RATE; NERVE CELL; PRIORITY JOURNAL; PROMOTER REGION; SIBLING; SIMPLEX AUTISM; SINGLE NUCLEOTIDE POLYMORPHISM; STRIATE CORTEX; TREND STUDY; ANIMAL; DNA MUTATIONAL ANALYSIS; FEMALE; GENETICS; GENOME-WIDE ASSOCIATION STUDY; HUMAN; INDEL MUTATION; MALE; MOUSE;

ANIMALS; AUTISTIC DISORDER; DNA COPY NUMBER VARIATIONS; DNA MUTATIONAL ANALYSIS; FEMALE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; INDEL MUTATION; MALE; MICE; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 85030709217     PISSN: 00928674     EISSN: 10974172     Source Type: Journal    
DOI: 10.1016/j.cell.2017.08.047     Document Type: Article

References (76)

1. Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., Rutter, M., Autism as a strongly genetic disorder: evidence from a British twin study. Psychol. Med. 25 (1995), 63–77.
2. Basu, S.N., Kollu, R., Banerjee-Basu, S., AutDB: a gene reference resource for autism research. Nucleic Acids Res. 37 (2009), D832–D836.
3. Brandler, W.M., Antaki, D., Gujral, M., Kleiber, M.L., Maile, M.S., Hong, O., Chapman, T.R., Tan, S., Tandon, P., Pang, T., et al. Paternally inherited noncoding structural variants contribute to autism. bioRxiv, 2017, 10.1101/102327.
4. Brandon, M.C., Ruiz-Pesini, E., Mishmar, D., Procaccio, V., Lott, M.T., Nguyen, K.C., Spolim, S., Patil, U., Baldi, P., Wallace, D.C., MITOMASTER: a bioinformatics tool for the analysis of mitochondrial DNA sequences. Hum. Mutat. 30 (2009), 1–6.
5. C Yuen, R.K., Merico, D., Bookman, M., L Howe, J., Thiruvahindrapuram, B., Patel, R.V., Whitney, J., Deflaux, N., Bingham, J., Wang, Z., et al. Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. Nat. Neurosci. 20 (2017), 602–611.
6. Carter, C.O., Genetics of common disorders. Br. Med. Bull. 25 (1969), 52–57.
7. Chen, F.C., Li, W.H., Genomic divergences between humans and other hominoids and the effective population size of the common ancestor of humans and chimpanzees. Am. J. Hum. Genet. 68 (2001), 444–456.
8. Chiang, C., Layer, R.M., Faust, G.G., Lindberg, M.R., Rose, D.B., Garrison, E.P., Marth, G.T., Quinlan, A.R., Hall, I.M., SpeedSeq: ultra-fast personal genome analysis and interpretation. Nat. Methods 12 (2015), 966–968.
9. Constantino, J.N., Recurrence rates in autism spectrum disorders. JAMA 312 (2014), 1154–1155.
10. Cotney, J., Muhle, R.A., Sanders, S.J., Liu, L., Willsey, A.J., Niu, W., Liu, W., Klei, L., Lei, J., Yin, J., et al. The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment. Nat. Commun., 6, 2015, 6404.
11. Danecek, P., McCarthy, S.A., BCFtools/csq: haplotype-aware variant consequences. Bioinformatics, 2017, 10.1093/bioinformatics/btx100 Published online February 16, 2017.
12. Davydov, E.V., Goode, D.L., Sirota, M., Cooper, G.M., Sidow, A., Batzoglou, S., Identifying a high fraction of the human genome to be under selective constraint using GERP++. PLoS Comput. Biol., 6, 2010, e1001025.
13. De Rubeis, S., He, X., Goldberg, A.P., Poultney, C.S., Samocha, K., Cicek, A.E., Kou, Y., Liu, L., Fromer, M., Walker, S., et al. DDD Study Homozygosity Mapping Collaborative for Autism, UK10K Consortium. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 515 (2014), 209–215.
14. Dong, F., Jiang, J., McSweeney, C., Zou, D., Liu, L., Mao, Y., Deletion of CTNNB1 in inhibitory circuitry contributes to autism-associated behavioral defects. Hum. Mol. Genet. 25 (2016), 2738–2751.
15. Dougherty, J.D., Schmidt, E.F., Nakajima, M., Heintz, N., Analytical approaches to RNA profiling data for the identification of genes enriched in specific cells. Nucleic Acids Res. 38 (2010), 4218–4230.
16. Durak, O., Gao, F., Kaeser-Woo, Y.J., Rueda, R., Martorell, A.J., Nott, A., Liu, C.Y., Watson, L.A., Tsai, L.H., Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling. Nat. Neurosci. 19 (2016), 1477–1488.
17. Durand, C.M., Betancur, C., Boeckers, T.M., Bockmann, J., Chaste, P., Fauchereau, F., Nygren, G., Rastam, M., Gillberg, I.C., Anckarsäter, H., et al. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat. Genet. 39 (2007), 25–27.
18. Eastwood, S.L., Walker, M., Hyde, T.M., Kleinman, J.E., Harrison, P.J., The DISC1 Ser704Cys substitution affects centrosomal localization of its binding partner PCM1 in glia in human brain. Hum. Mol. Genet. 19 (2010), 2487–2496.
19. Ernst, J., Kellis, M., ChromHMM: automating chromatin-state discovery and characterization. Nat. Methods 9 (2012), 215–216.
20. Fischbach, G.D., Lord, C., The Simons Simplex Collection: a resource for identification of autism genetic risk factors. Neuron 68 (2010), 192–195.
21. Fombonne, E., Epidemiological surveys of autism and other pervasive developmental disorders: an update. J. Autism Dev. Disord. 33 (2003), 365–382.
22. Fuccillo, M.V., Striatal circuits as a common node for autism pathophysiology. Front. Neurosci., 10, 2016, 27.
23. Gaugler, T., Klei, L., Sanders, S.J., Bodea, C.A., Goldberg, A.P., Lee, A.B., Mahajan, M., Manaa, D., Pawitan, Y., Reichert, J., et al. Most genetic risk for autism resides with common variation. Nat. Genet. 46 (2014), 881–885.
24. Girirajan, S., Rosenfeld, J.A., Cooper, G.M., Antonacci, F., Siswara, P., Itsara, A., Vives, L., Walsh, T., McCarthy, S.E., Baker, C., et al. A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nat. Genet. 42 (2010), 203–209.
25. Gratten, J., Wray, N.R., Peyrot, W.J., McGrath, J.J., Visscher, P.M., Goddard, M.E., Risk of psychiatric illness from advanced paternal age is not predominantly from de novo mutations. Nat. Genet. 48 (2016), 718–724.
26. Hach, F., Hormozdiari, F., Alkan, C., Hormozdiari, F., Birol, I., Eichler, E.E., Sahinalp, S.C., mrsFAST: a cache-oblivious algorithm for short-read mapping. Nat. Methods 7 (2010), 576–577.
27. Hallmayer, J., Cleveland, S., Torres, A., Phillips, J., Cohen, B., Torigoe, T., Miller, J., Fedele, A., Collins, J., Smith, K., et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch. Gen. Psychiatry 68 (2011), 1095–1102.
28. Handsaker, R.E., Korn, J.M., Nemesh, J., McCarroll, S.A., Discovery and genotyping of genome structural polymorphism by sequencing on a population scale. Nat. Genet. 43 (2011), 269–276.
29. Hashimoto, R., Nakazawa, T., Tsurusaki, Y., Yasuda, Y., Nagayasu, K., Matsumura, K., Kawashima, H., Yamamori, H., Fujimoto, M., Ohi, K., et al. Whole-exome sequencing and neurite outgrowth analysis in autism spectrum disorder. J. Hum. Genet. 61 (2016), 199–206.
30. Hormozdiari, F., Hajirasouliha, I., McPherson, A., Eichler, E.E., Sahinalp, S.C., Simultaneous structural variation discovery among multiple paired-end sequenced genomes. Genome Res. 21 (2011), 2203–2212.
31. Hormozdiari, F., Penn, O., Borenstein, E., Eichler, E.E., The discovery of integrated gene networks for autism and related disorders. Genome Res. 25 (2015), 142–154.
32. Hoyer, J., Ekici, A.B., Endele, S., Popp, B., Zweier, C., Wiesener, A., Wohlleber, E., Dufke, A., Rossier, E., Petsch, C., et al. Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex, is a frequent cause of intellectual disability. Am. J. Hum. Genet. 90 (2012), 565–572.
33. Iossifov, I., Ronemus, M., Levy, D., Wang, Z., Hakker, I., Rosenbaum, J., Yamrom, B., Lee, Y.H., Narzisi, G., Leotta, A., et al. De novo gene disruptions in children on the autistic spectrum. Neuron 74 (2012), 285–299.
34. Iossifov, I., O'Roak, B.J., Sanders, S.J., Ronemus, M., Krumm, N., Levy, D., Stessman, H.A., Witherspoon, K.T., Vives, L., Patterson, K.E., et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature 515 (2014), 216–221.
35. Jacquemont, S., Coe, B.P., Hersch, M., Duyzend, M.H., Krumm, N., Bergmann, S., Beckmann, J.S., Rosenfeld, J.A., Eichler, E.E., A higher mutational burden in females supports a “female protective model” in neurodevelopmental disorders. Am. J. Hum. Genet. 94 (2014), 415–425.
36. Jiang, Y.H., Sahoo, T., Michaelis, R.C., Bercovich, D., Bressler, J., Kashork, C.D., Liu, Q., Shaffer, L.G., Schroer, R.J., Stockton, D.W., et al. A mixed epigenetic/genetic model for oligogenic inheritance of autism with a limited role for UBE3A. Am. J. Med. Genet. A. 131 (2004), 1–10.
37. Jiang, Y.H., Yuen, R.K., Jin, X., Wang, M., Chen, N., Wu, X., Ju, J., Mei, J., Shi, Y., He, M., et al. Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing. Am. J. Hum. Genet. 93 (2013), 249–263.
38. Katayama, Y., Nishiyama, M., Shoji, H., Ohkawa, Y., Kawamura, A., Sato, T., Suyama, M., Takumi, T., Miyakawa, T., Nakayama, K.I., CHD8 haploinsufficiency results in autistic-like phenotypes in mice. Nature 537 (2016), 675–679.
39. Kircher, M., Witten, D.M., Jain, P., O'Roak, B.J., Cooper, G.M., Shendure, J., A general framework for estimating the relative pathogenicity of human genetic variants. Nat. Genet. 46 (2014), 310–315.
40. Kong, A., Frigge, M.L., Masson, G., Besenbacher, S., Sulem, P., Magnusson, G., Gudjonsson, S.A., Sigurdsson, A., Jonasdottir, A., Jonasdottir, A., et al. Rate of de novo mutations and the importance of father's age to disease risk. Nature 488 (2012), 471–475.
41. Kong, S.W., Collins, C.D., Shimizu-Motohashi, Y., Holm, I.A., Campbell, M.G., Lee, I.H., Brewster, S.J., Hanson, E., Harris, H.K., Lowe, K.R., et al. Characteristics and predictive value of blood transcriptome signature in males with autism spectrum disorders. PLoS ONE, 7, 2012, e49475.
42. Konopka, G., Wexler, E., Rosen, E., Mukamel, Z., Osborn, G.E., Chen, L., Lu, D., Gao, F., Gao, K., Lowe, J.K., Geschwind, D.H., Modeling the functional genomics of autism using human neurons. Mol. Psychiatry 17 (2012), 202–214.
43. Kronenberg, Z.N., Osborne, E.J., Cone, K.R., Kennedy, B.J., Domyan, E.T., Shapiro, M.D., Elde, N.C., Yandell, M., Wham: identifying structural variants of biological consequence. PLoS Comput. Biol., 11, 2015, e1004572.
44. Krumm, N., Turner, T.N., Baker, C., Vives, L., Mohajeri, K., Witherspoon, K., Raja, A., Coe, B.P., Stessman, H.A., He, Z.X., et al. Excess of rare, inherited truncating mutations in autism. Nat. Genet. 47 (2015), 582–588.
45. Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., Ziller, M.J., et al., Roadmap Epigenomics Consortium. Integrative analysis of 111 reference human epigenomes. Nature 518 (2015), 317–330.
46. Layer, R.M., Chiang, C., Quinlan, A.R., Hall, I.M., LUMPY: a probabilistic framework for structural variant discovery. Genome Biol., 15, 2014, R84.
47. Lee, H., Lin, M.C., Kornblum, H.I., Papazian, D.M., Nelson, S.F., Exome sequencing identifies de novo gain of function missense mutation in KCND2 in identical twins with autism and seizures that slows potassium channel inactivation. Hum. Mol. Genet. 23 (2014), 3481–3489.
48. Levy, D., Ronemus, M., Yamrom, B., Lee, Y.H., Leotta, A., Kendall, J., Marks, S., Lakshmi, B., Pai, D., Ye, K., et al. Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron 70 (2011), 886–897.
49. Li, H., Durbin, R., Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26 (2010), 589–595.
50. Liu, G.E., Alkan, C., Jiang, L., Zhao, S., Eichler, E.E., Comparative analysis of Alu repeats in primate genomes. Genome Res. 19 (2009), 876–885.
51. Manichaikul, A., Mychaleckyj, J.C., Rich, S.S., Daly, K., Sale, M., Chen, W.M., Robust relationship inference in genome-wide association studies. Bioinformatics 26 (2010), 2867–2873.
52. Marchetto, M.C., Belinson, H., Tian, Y., Freitas, B.C., Fu, C., Vadodaria, K.C., Beltrao-Braga, P.C., Trujillo, C.A., Mendes, A.P., Padmanabhan, K., et al. Altered proliferation and networks in neural cells derived from idiopathic autistic individuals. Mol. Psychiatry 22 (2016), 820–835.
53. McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., Garimella, K., Altshuler, D., Gabriel, S., Daly, M., DePristo, M.A., The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20 (2010), 1297–1303.
54. Moreno-Ramos, O.A., Olivares, A.M., Haider, N.B., de Autismo, L.C., Lattig, M.C., Whole-exome sequencing in a South American cohort links ALDH1A3, FOXN1 and retinoic acid regulation pathways to autism spectrum disorders. PLoS ONE, 10, 2015, e0135927.
55. O'Roak, B.J., Deriziotis, P., Lee, C., Vives, L., Schwartz, J.J., Girirajan, S., Karakoc, E., Mackenzie, A.P., Ng, S.B., Baker, C., et al. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat. Genet. 43 (2011), 585–589.
56. O'Roak, B.J., Vives, L., Fu, W., Egertson, J.D., Stanaway, I.B., Phelps, I.G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., et al. Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science 338 (2012), 1619–1622.
57. O'Roak, B.J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B.P., Levy, R., Ko, A., Lee, C., Smith, J.D., et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 485 (2012), 246–250.
58. Pennacchio, L.A., Ahituv, N., Moses, A.M., Prabhakar, S., Nobrega, M.A., Shoukry, M., Minovitsky, S., Dubchak, I., Holt, A., Lewis, K.D., et al. In vivo enhancer analysis of human conserved non-coding sequences. Nature 444 (2006), 499–502.
59. Pinto, D., Delaby, E., Merico, D., Barbosa, M., Merikangas, A., Klei, L., Thiruvahindrapuram, B., Xu, X., Ziman, R., Wang, Z., et al. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am. J. Hum. Genet. 94 (2014), 677–694.
60. Sanders, S.J., Ercan-Sencicek, A.G., Hus, V., Luo, R., Murtha, M.T., Moreno-De-Luca, D., Chu, S.H., Moreau, M.P., Gupta, A.R., Thomson, S.A., et al. Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron 70 (2011), 863–885.
61. 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. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 485 (2012), 237–241.
62. Schaaf, C.P., Sabo, A., Sakai, Y., Crosby, J., Muzny, D., Hawes, A., Lewis, L., Akbar, H., Varghese, R., Boerwinkle, E., et al. Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders. Hum. Mol. Genet. 20 (2011), 3366–3375.
63. She, X., Liu, G., Ventura, M., Zhao, S., Misceo, D., Roberto, R., Cardone, M.F., Rocchi, M., Green, E.D., Archidiacano, N., Eichler, E.E., NISC Comparative Sequencing Program. A preliminary comparative analysis of primate segmental duplications shows elevated substitution rates and a great-ape expansion of intrachromosomal duplications. Genome Res. 16 (2006), 576–583.
64. Steffenburg, S., Gillberg, C., Hellgren, L., Andersson, L., Gillberg, I.C., Jakobsson, G., Bohman, M., A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J. Child Psychol. Psychiatry 30 (1989), 405–416.
65. Sudmant, P.H., Kitzman, J.O., Antonacci, F., Alkan, C., Malig, M., Tsalenko, A., Sampas, N., Bruhn, L., Shendure, J., Eichler, E.E., 1000 Genomes Project. Diversity of human copy number variation and multicopy genes. Science 330 (2010), 641–646.
66. Sudmant, P.H., Mallick, S., Nelson, B.J., Hormozdiari, F., Krumm, N., Huddleston, J., Coe, B.P., Baker, C., Nordenfelt, S., Bamshad, M., et al. Global diversity, population stratification, and selection of human copy number variation. Science, 11, 2015, 349.
67. Sudmant, P.H., Rausch, T., Gardner, E.J., Handsaker, R.E., Abyzov, A., Huddleston, J., Zhang, Y., Ye, K., Jun, G., Hsi-Yang Fritz, M., et al. An integrated map of structural variation in 2,504 human genomes. Nature 526 (2015), 75–81.
68. Tavassoli, T., Kolevzon, A., Wang, A.T., Curchack-Lichtin, J., Halpern, D., Schwartz, L., Soffes, S., Bush, L., Grodberg, D., Cai, G., Buxbaum, J.D., De novo SCN2A splice site mutation in a boy with Autism spectrum disorder. BMC Med. Genet., 15, 2014, 35.
69. Turner, T., Pihur, V., Chakravarti, A., Quantifying and modeling birth order effects in autism. PLoS ONE, 6, 2011, e26418.
70. Turner, T.N., Sharma, K., Oh, E.C., Liu, Y.P., Collins, R.L., Sosa, M.X., Auer, D.R., Brand, H., Sanders, S.J., Moreno-De-Luca, D., et al. Loss of δ-catenin function in severe autism. Nature 520 (2015), 51–56.
71. Turner, T.N., Hormozdiari, F., Duyzend, M.H., McClymont, S.A., Hook, P.W., Iossifov, I., Raja, A., Baker, C., Hoekzema, K., Stessman, H.A., et al. Genome sequencing of autism-affected families reveals disruption of putative noncoding regulatory DNA. Am. J. Hum. Genet. 98 (2016), 58–74.
72. Visel, A., Minovitsky, S., Dubchak, I., Pennacchio, L.A., VISTA enhancer browser-a database of tissue-specific human enhancers. Nucleic Acids Res. 35 (2007), D88–D92.
73. Voineagu, I., Wang, X., Johnston, P., Lowe, J.K., Tian, Y., Horvath, S., Mill, J., Cantor, R.M., Blencowe, B.J., Geschwind, D.H., Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature 474 (2011), 380–384.
74. Werling, D.M., Brand, H., An, J.-Y., Stone, M.R., Glessner, J.T., Zhu, L., Collins, R.L., Dong, S., Layer, R.M., Markenscoff-Papadimitriou, E.-C., et al. Limited contribution of rare, noncoding variation to autism spectrum disorder from sequencing of 2,076 genomes in quartet families. bioRxiv, 2017, 10.1101/127043.
75. Xu, X., Wells, A.B., O'Brien, D.R., Nehorai, A., Dougherty, J.D., Cell type-specific expression analysis to identify putative cellular mechanisms for neurogenetic disorders. J. Neurosci. 34 (2014), 1420–1431.
76. Yuen, R.K., Merico, D., Cao, H., Pellecchia, G., Alipanahi, B., Thiruvahindrapuram, B., Tong, X., Sun, Y., Cao, D., Zhang, T., et al. Genome-wide characteristics of de novo mutations in autism. NPJ Genom. Med., 1, 2016 160271-1602710.