Whole-Genome Sequencing in Autism Identifies Hot Spots for De Novo Germline Mutation
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De novo mutation plays an important role in autism spectrum disorders (ASDs). Notably, pathogenic copy number variants (CNVs) are characterized by high mutation rates. We hypothesize that hypermutability is a property of ASD genes and may also include nucleotide-substitution hot spots. We investigated global patterns of germline mutation by whole-genome sequencing of monozygotic twins concordant for ASD and their parents. Mutation rates varied widely throughout the genome (by 100-fold) and could be explained by intrinsic characteristics of DNA sequence and chromatin structure. Dense clusters of mutations within individual genomes were attributable to compound mutation or gene conversion. Hypermutability was a characteristic of genes involved in ASD and other diseases. In addition, genes impacted by mutations in this study were associated with ASD in independent exome-sequencing data sets. Our findings suggest that regional hypermutation is a significant factor shaping patterns of genetic variation and disease risk in humans.
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Advanced paternal age correlates with increased rates of germline mutation in offspring.
“We and others have demonstrated that advanced paternal age correlates with increased rates of germline mutation in offspring28–30”
From A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex (2022) · cites this paper as [28]
About 70% of de novo mutations are paternal, and the total new mutation rate in offspring increases by 1-2 mutations per year with paternal age.
“Thus, a majority (70%) of de novo mutations originate from the father and total rate of new mutations in offspring increase by 1–2 mutations per year with his age (Kong et al., 2012; Michaelson et al., 2012).”
From Getting to the cores of autism (2019) · cites this paper as Michaelson et al., 2012
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Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
Regularization Paths for Generalized Linear Models via Coordinate Descent
Friedman, J., Hastie, T., & Tibshirani, R. (2010) · Journal of Statistical Software · doi:10.18637/jss.v033.i01 · Cited by 19,927 · see citing works
A framework for variation discovery and genotyping using next-generation DNA sequencing data
DePristo, M. A., Banks, E., Poplin, R. E., Garimella, K. V., Maguire, J., Hartl, C., Philippakis, A., del Angel, G., Rivas, M. A., Hanna, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.806 · Cited by 11,216 · see citing works
Hindorff, L. A., Sethupathy, P., Junkins, H. A., Ramos, E. M., Mehta, J. P., Collins, F. S., & Manolio, T. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903103106 · Cited by 4,013 · see citing works
Strong association of de novo copy number mutations with autism
Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., et al. (2007) · Science · doi:10.1126/science.1138659 · Cited by 2,795 · see citing works
Self-citationInitial sequence of the chimpanzee genome and comparison with the human genome
The Chimpanzee Sequencing and Analysis Consortium (2005) · Nature · doi:10.1038/nature04072 · Cited by 2,459 · see citing works
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
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. (2012) · Nature · doi:10.1038/nature10989 · Cited by 2,165 · cited 8× · see citing works
“…correlated with mutation rate variation in a genome-wide data set from two trios (Conrad et al., 2011) (Figure 4B) and exome data sets from four independent trio-based studies of autism (Iossifov et al., 2012; Neale et al., 2012; O’Roak et al., 2011, 2012; Sanders et al., 2012) (Figures 4C and 4D).”
InfluentialRate of de novo mutations and the importance of father’s age to disease risk
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) · Nature · doi:10.1038/nature11396 · Cited by 2,134 · see citing works
De novo mutations revealed by whole-exome sequencing are strongly associated with autism
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) · Nature · doi:10.1038/nature10945 · Cited by 2,084 · see citing works
Patterns and rates of exonic de novo mutations in autism spectrum disorders
Neale, B. M., Kou, Y., Liu, L., Ma’ayan, A., Samocha, K. E., Sabo, A., Lin, C.-F., Stevens, C., Wang, L.-S., Makarov, V., et al. (2012) · Nature · doi:10.1038/nature11011 · Cited by 1,734 · see citing works
De Novo Gene Disruptions in Children on the Autistic Spectrum
Iossifov, I., Ronemus, M., Levy, D., Wang, Z., Hakker, I., Rosenbaum, J., Yamrom, B., Lee, Y.-H., Narzisi, G., Leotta, A., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.04.009 · Cited by 1,446 · see citing works
Estimate of the Mutation Rate per Nucleotide in Humans
Nachman, M. W., & Crowell, S. L. (2000) · Genetics · doi:10.1093/genetics/156.1.297 · Cited by 1,214 · see citing works
Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations
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. (2011) · Nature Genetics · doi:10.1038/ng.835 · Cited by 1,203 · see citing works
Molecular basis of base substitution hotspots in Escherichia coli
Coulondre, C., Miller, J. H., Farabaugh, P. J., & Gilbert, W. (1978) · Nature · doi:10.1038/274775a0 · Cited by 1,193 · see citing works
The origins, patterns and implications of human spontaneous mutation
Crow, J. F. (2000) · Nature Reviews Genetics · doi:10.1038/35049558 · Cited by 928 · see citing works
Lupski, J. R. (1998) · Trends in Genetics · doi:10.1016/s0168-9525(98)01555-8 · Cited by 908 · see citing works
CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics
Malhotra, D., & Sebat, J. (2012) · Cell · doi:10.1016/j.cell.2012.02.039 · Cited by 854 · see citing works
Self-citationRate, molecular spectrum, and consequences of human mutation
Lynch, M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912629107 · Cited by 792 · see citing works
Gene conversion: mechanisms, evolution and human disease
Chen, J., Cooper, D. N., Chuzhanova, N. A., Férec, C., & Patrinos, G. P. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2193 · Cited by 689 · see citing works
Chromatin organization is a major influence on regional mutation rates in human cancer cells
Schuster-Böckler, B., & Lehner, B. (2012) · Nature · doi:10.1038/nature11273 · Cited by 657 · cited 2× · see citing works
“, 2012) and cancer (Schuster-Böckler and Lehner, 2012) is also influenced by aspects of chromatin structure, consistent with partially overlappingmutational mechanisms acting in germ cells and somatic cells.”
Siva, N. (2008) · Nature Biotechnology · doi:10.1038/nbt0308-256b · Cited by 629 · see citing works
Deletions of Chromosome 15 as a Cause of the Prader–Willi Syndrome
Ledbetter, D. H., Riccardi, V. M., Airhart, S. D., Strobel, R. J., Keenan, B. S., & Crawford, J. D. (1981) · New England Journal of Medicine · doi:10.1056/nejm198102053040604 · Cited by 622 · see citing works
Revising the human mutation rate: implications for understanding human evolution
Scally, A., & Durbin, R. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3295 · Cited by 610 · see citing works
Variation in genome-wide mutation rates within and between human families
the 1000 Genomes Project (2011) · Nature Genetics · doi:10.1038/ng.862 · Cited by 581 · see citing works
Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation
Berkel, S., Marshall, C. R., Weiss, B., Howe, J., Roeth, R., Moog, U., Endris, V., Roberts, W., Szatmari, P., Pinto, D., et al. (2010) · Nature Genetics · doi:10.1038/ng.589 · Cited by 563 · see citing works
The rate of spontaneous mutation of a human gene
Haldane, J. B. S. (2004) · Journal of Genetics · doi:10.1007/bf02717892 · Cited by 472 · see citing works
Clinical application of exome sequencing in undiagnosed genetic conditions
Need, A. C., Shashi, V., Hitomi, Y., Schoch, K., Shianna, K. V., McDonald, M., Meisler, M. H., & Goldstein, D. B. (2012) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2012-100819 · Cited by 438 · see citing works
Nelis, E., & Broeckhoven, C. V. (1996) · European Journal of Human Genetics · doi:10.1159/000472166 · Cited by 431 · see citing works
Genomic rearrangements and sporadic disease
Lupski, J. R. (2007) · Nature Genetics · doi:10.1038/ng2084 · Cited by 424 · see citing works
Evolving responsively: adaptive mutation
Rosenberg, S. M. (2001) · Nature Reviews Genetics · doi:10.1038/35080556 · Cited by 417 · see citing works
Mechanisms of transcription-coupled DNA repair
Svejstrup, J. Q. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm703 · Cited by 380 · see citing works
Human SNP variability and mutation rate are higher in regions of high recombination
Lercher, M. J., & Hurst, L. D. (2002) · Trends in Genetics · doi:10.1016/s0168-9525(02)02669-0 · Cited by 367 · see citing works
A direct characterization of human mutation based on microsatellites
Sun, J. X., Helgason, A., Másson, G., Ebenesersdóttir, S. S., Li, H., Mallick, S., Gnerre, S., Patterson, N. J., Kong, A., Reich, D., et al. (2012) · Nature Genetics · doi:10.1038/ng.2398 · Cited by 342 · see citing works
High frequencies of de novo CNVs in bipolar disorder and schizophrenia
Malhotra, D., McCarthy, S., Michaelson, J. J., Vacic, V., Burdick, K. E., Yoon, S., Cichon, S., Corvin, A., Gary, S., Gershon, E. S., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.11.007 · Cited by 325 · cited 1× · see citing works
“Based on experience from our earlier CNV-based studies of DNM (Malhotra et al., 2011; Nord et al., 2011; Sebat et al., 2007), an unfiltered set of putative DNMs is highly enriched for errors.”
Self-citationAmiel, J., Rio, M., Pontual, L. D., Redon, R., Malan, V., Boddaert, N., Plouin, P., Carter, N. P., Lyonnet, S., Munnich, A., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/515582 · Cited by 319 · see citing works
Zweier, C., Peippo, M. M., Hoyer, J., Sousa, S., Bottani, A., Clayton-Smith, J., Reardon, W., Saraiva, J., Cabral, A., Göhring, I., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/515583 · Cited by 317 · see citing works
The histone code at DNA breaks: a guide to repair?
van Attikum, H., & Gasser, S. M. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1737 · Cited by 301 · see citing works
Hardison, R. C., Roskin, K., Yang, S., Diekhans, M., Kent, W. J., Weber, R., Elnitski, L., Li, J., O'Connor, M., Kolbe, D., et al. (2003) · Genome Research · doi:10.1101/gr.844103 · Cited by 280 · see citing works
Koren, A., Polak, P., Nemesh, J., Michaelson, J. J., Sebat, J., Sunyaev, S., & Mccarroll, S. (2012) · American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.10.018 · Cited by 246 · see citing works
Self-citationProtein interactome reveals converging molecular pathways among autism disorders
Sakai, Y., Shaw, C. A., Dawson, B. C., Dugas, D. V., Al-Mohtaseb, Z., Hill, D. E., & Zoghbi, H. Y. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002166 · Cited by 226 · see citing works
Estimating the human mutation rate using autozygosity in a founder population.
Campbell, C. D., Chong, J. X., Malig, M., Ko, A., Dumont, B. L., Han, L., Vives, L., O'Roak, B. J., Sudmant, P. H., Shendure, J., et al. (2012) · Nature Genetics · doi:10.1038/ng.2418 · Cited by 215 · see citing works
The role of genetic variation in the causation of mental illness: an evolution-informed framework
Uher, R. (2009) · Molecular Psychiatry · doi:10.1038/mp.2009.85 · Cited by 189 · see citing works
OGEE: an online gene essentiality database
Chen, W., Mínguez, P., Lercher, M. J., & Peer Bork, B. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr986 · Cited by 183 · see citing works
Laumonnier, F., Roger, S., Guérin, P., Molinari, F., Mrad, R., Cahard, D., Belhadj, A., Halayem, M. B., Persico, A. M., Elia, M., et al. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.9.1622 · Cited by 180 · see citing works
Talkowski, M. E., Ernst, C., Heilbut, A. M., Chiang, C., Hanscom, C., Lindgren, A. M., Kirby, A. W., Liu, S., Muddukrishna, B., Ohsumi, T. K., et al. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.03.013 · Cited by 177 · see citing works
Mutation rate variation in the mammalian genome
Ellegren, H., Smith, N. G. C., & Webster, M. T. (2003) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2003.10.008 · Cited by 159 · see citing works
Ninio, J. (1991) · Genetics · doi:10.1093/genetics/129.3.957 · Cited by 150 · see citing works
Why do human diversity levels vary at a megabase scale?Preprint
Hellmann, I., Prüfer, K., Ji, H., Zody, M. C., Pääbo, S., & Ptak, S. E. (2005) · Genome Research · doi:10.1101/gr.3461105 · Cited by 148 · see citing works
Pervasive Multinucleotide Mutational Events in Eukaryotes
Schrider, D. R., Hourmozdi, J., & Hahn, M. W. (2011) · Current Biology · doi:10.1016/j.cub.2011.05.013 · Cited by 144 · see citing works
Predicting Human Nucleosome Occupancy from Primary Sequence
Gupta, S., Dennis, J. H., Thurman, R. E., et al. (2008) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000134 · Cited by 134 · see citing works
Raychaudhuri, S., Korn, J. M., McCarroll, S. A., The International Schizophrenia Consortium, Altshuler, D., Sklar, P., Purcell, S., & Daly, M. J. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001097 · Cited by 131 · see citing works
Self-citationReduced transcript expression of genes affected by inherited and de novo CNVs in autism
STAART Psychopharmacology Network, Nord, A. S., Roeb, W., Dickel, D. E., Walsh, T., Kusenda, M., O’Connor, K. L., Malhotra, D., McCarthy, S., Stray, S. M., et al. (2011) · European Journal of Human Genetics · doi:10.1038/ejhg.2011.24 · Cited by 125 · see citing works
Self-citationA molecular approach to estimating the human deleterious mutation rate
Kondrashov, A. S., & Crow, J. F. (1993) · Human Mutation · doi:10.1002/humu.1380020312 · Cited by 118 · see citing works
Isochores result from mutation not selection
Francino, M. P., & Ochman, H. (1999) · Nature · doi:10.1038/21804 · Cited by 103 · see citing works
Rattray, A. J., Shafer, B. K., McGill, C. B., & Strathern, J. N. (2002) · Genetics · doi:10.1093/genetics/162.3.1063 · Cited by 101 · see citing works
Mutator phenotypes due to DNA replication infidelity
Arana, M. E., & Kunkel, T. A. (2010) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2010.10.003 · Cited by 96 · see citing works
Compositional Evolution of Noncoding DNA in the Human and Chimpanzee Genomes
Webster, M. T. (2003) · Molecular Biology and Evolution · doi:10.1093/molbev/msg037 · Cited by 79 · see citing works
Wang, J., Hagman, K. D. F., Scaringe, W. A., Tsai, K., Liu, N., Gu, D., Li, W., Hill, K. A., & Sommer, S. S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610902104 · Cited by 74 · see citing works
Self-citationforestSV: structural variant discovery through statistical learning
Michaelson, J. J., & Sebat, J. L. (2012) · Nature Methods · doi:10.1038/nmeth.2085 · Cited by 52 · see citing works
Self-citationHuang, X., Zou, Y. S., Maher, T. A., Newton, S. A., & Milunsky, J. M. (2010) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33497 · Cited by 51 · see citing works
Hurles, M. E. (2002) · Science · doi:10.1126/science.298.5598.1509a · Cited by 26 · see citing works
Hamdan, F. F., Daoud, H., Patry, L., Dionne‐Laporte, A., Spiegelman, D., Dobrzeniecka, S., Rouleau, G. A., & Michaud, J. L. (2012) · Clinical Genetics · doi:10.1111/j.1399-0004.2012.01890.x · Cited by 20 · see citing works
Flagged first, then by citations
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The contribution of de novo coding mutations to autism spectrum disorder
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. (2014) · Nature · doi:10.1038/nature13908 · Cited by 2,585 · see citing works
Lai, M.-C., Lombardo, M. V., & Baron-Cohen, S. (2014) · The Lancet · doi:10.1016/s0140-6736(13)61539-1 · Cited by 2,371 · see citing works
Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism
Parikshak, N. N., Luo, R., Zhang, A., Won, H., Lowe, J. K., Chandran, V., Horvath, S., & Geschwind, D. H. (2013) · Cell · doi:10.1016/j.cell.2013.10.031 · Cited by 1,039 · see citing works
Genome sequencing identifies major causes of severe intellectual disability
Gilissen, C., Hehir-Kwa, J. Y., Thung, D. T., van de Vorst, M., van Bon, B. W. M., Willemsen, M. H., Kwint, M., Janssen, I. M., Hoischen, A., Schenck, A., et al. (2014) · Nature · doi:10.1038/nature13394 · Cited by 1,125 · see citing works
From the genetic architecture to synaptic plasticity in autism spectrum disorder
Bourgeron, T. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3992 · Cited by 975 · see citing works
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
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. (2017) · Nature Neuroscience · doi:10.1038/nn.4524 · Cited by 844 · see citing works
Somatic mutation, genomic variation, and neurological disease
Poduri, A., Evrony, G. D., Cai, X., & Walsh, C. A. (2013) · Science · doi:10.1126/science.1237758 · Cited by 584 · see citing works
Inherited and de novo genetic risk for autism impacts shared networks
Ruzzo, E. K., Pérez-Cano, L., Jung, J.-Y., Wang, L.-K., Kashef-Haghighi, D., Hartl, C., Singh, C., Xu, J., Hoekstra, J. N., Leventhal, O., et al. (2019) · Cell · doi:10.1016/j.cell.2019.07.015 · Cited by 457 · see citing works
Comorbidity clusters in autism spectrum disorders: an electronic health record time-series analysis
Doshi-Velez, F., Ge, Y., & Kohane, I. (2014) · Pediatrics · doi:10.1542/peds.2013-0819 · Cited by 412 · see citing works
Large-scale genomics unveils the genetic architecture of psychiatric disorders
Gratten, J., Wray, N. R., Keller, M. C., & Visscher, P. M. (2014) · Nature Neuroscience · doi:10.1038/nn.3708 · Cited by 363 · see citing works
Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity
Coe, B. P., Stessman, H. A. F., Sulovari, A., Geisheker, M. R., Bakken, T. E., Lake, A. M., Dougherty, J. D., Lein, E. S., Hormozdiari, F., Bernier, R. A., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0288-4 · Cited by 330 · see citing works
Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder
An, J.-Y., Lin, K., Zhu, L., Werling, D. M., Dong, S., Brand, H., Wang, H. Z., Zhao, X., Schwartz, G. B., Collins, R. L., et al. (2018) · Science · doi:10.1126/science.aat6576 · Cited by 316 · see citing works
Kosmicki, J. A., Samocha, K. E., Howrigan, D. P., Sanders, S. J., Slowikowski, K., Lek, M., Karczewski, K. J., Cutler, D. J., Devlin, B., Roeder, K., et al. (2017) · Nature Genetics · doi:10.1038/ng.3789 · Cited by 340 · see citing works
Pottier, C., Bieniek, K. F., Finch, N., van de Vorst, M., Baker, M., Perkersen, R., Brown, P., Ravenscroft, T., van Blitterswijk, M., Nicholson, A. M., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1436-x · Cited by 312 · see citing works
Determinants of Mutation Rate Variation in the Human Germline
Ségurel, L., Wyman, M. J., & Przeworski, M. (2014) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-031714-125740 · Cited by 289 · see citing works
Getting to the cores of autism
Iakoucheva, L. M., Muotri, A. R., & Sebat, J. (2019) · Cell · doi:10.1016/j.cell.2019.07.037 · Cited by 260 · see citing works
Self-citationMandy, W., & Lai, M. (2016) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12501 · Cited by 283 · see citing works
The Emerging Picture of Autism Spectrum Disorder: Genetics and Pathology
Chen, J. A., Peñagarikano, O., Belgard, T. G., Swarup, V., & Geschwind, D. H. (2015) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012414-040405 · Cited by 254 · see citing works
Paternally inherited cis-regulatory structural variants are associated with autism
Brandler, W. M., Antaki, D., Gujral, M., Kleiber, M. L., Whitney, J., Maile, M. S., Hong, O., Chapman, T. R., Tan, S., Tandon, P., et al. (2018) · Science · doi:10.1126/science.aan2261 · Cited by 209 · see citing works
Self-citationPatterns of de novo tandem repeat mutations and their role in autism
Mitra, I., Huang, B., Mousavi, N., Ma, N., Lamkin, M., Yanicky, R., Shleizer-Burko, S., Lohmueller, K. E., & Gymrek, M. (2021) · Nature · doi:10.1038/s41586-020-03078-7 · Cited by 194 · see citing works
Antaki, D., Guevara, J., Maihofer, A. X., Klein, M., Gujral, M., Grove, J., Carey, C. E., Hong, O., Arranz, M. J., Hervas, A., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01064-5 · Cited by 206 · see citing works
Self-citationSkuse, D. H., Lori, A., Cubells, J. F., Lee, I., Conneely, K. N., Puura, K., Lehtimäki, T., Binder, E. B., & Young, L. J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1302985111 · Cited by 207 · see citing works
Zhang, Y., Li, N., Li, C., Zhang, Z., Teng, H., Wang, Y., Zhao, T., Shi, L., Zhang, K., Xia, K., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0699-8 · Cited by 177 · see citing works
Self-citationJanecka, M., Mill, J., Basson, M. A., Goriely, A., Spiers, H., Reichenberg, A., Schalkwyk, L., & Fernandes, C. (2017) · Translational Psychiatry · doi:10.1038/tp.2016.294 · Cited by 140 · see citing works
Recurrent de novo mutations in neurodevelopmental disorders: properties and clinical implications
Wilfert, A. B., Sulovari, A., Turner, T. N., Coe, B. P., & Eichler, E. E. (2017) · Genome Medicine · doi:10.1186/s13073-017-0498-x · Cited by 144 · see citing works
Corominas, R., Yang, X., Lin, G. N., Kang, S., Shen, Y., Ghamsari, L., Broly, M., Rodriguez, M., Tam, S., Wanamaker, S. A., et al. (2014) · Nature Communications · doi:10.1038/ncomms4650 · Cited by 140 · see citing works
“Recently, de novo point mutations of TCF4 have been implicated in developmental delay 41–43 and autism 35 , and common variants of TCF4 were recurrently implicated in schizophrenia 44,45 .”
Self-citation<i>KCTD</i>: A new gene family involved in neurodevelopmental and neuropsychiatric disorders
Teng, X., Aouacheria, A., Lionnard, L., Metz, K. A., Soane, L., Kamiya, A., & Hardwick, J. M. (2019) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13156 · Cited by 124 · see citing works
Epigenetics of Autism Spectrum Disorder
Siu, M. T., & Weksberg, R. (2017) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-53889-1_4 · Cited by 121 · see citing works
Risk of psychiatric illness from advanced paternal age is not predominantly from de novo mutations
Gratten, J., Wray, N. R., Peyrot, W. J., McGrath, J. J., Visscher, P. M., & Goddard, M. E. (2016) · Nature Genetics · doi:10.1038/ng.3577 · Cited by 118 · see citing works
Frequency and complexity of de novo structural mutation in autism
Brandler, W. M., Antaki, D., Gujral, M., Noor, A., Rosanio, G., Chapman, T. R., Barrera, D. J., Lin, G. N., Malhotra, D., Watts, A. C., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.02.018 · Cited by 104 · see citing works
Self-citationDrug discovery for autism spectrum disorder: challenges and opportunities
Ghosh, A., Michalon, A., Lindemann, L., Fontoura, P., & Santarelli, L. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4102 · Cited by 108 · see citing works
Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism
Liu, X., Han, D., Somel, M., Jiang, X., Hu, H., Guijarro, P., Zhang, N., Mitchell, A., Halene, T., Ely, J. J., et al. (2016) · PLOS Biology · doi:10.1371/journal.pbio.1002558 · Cited by 87 · see citing works
Wang, W., Corominas, R., & Lin, G. N. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00258 · Cited by 70 · see citing works
Self-citationAutism Spectrum Disorder Genetics: Diverse Genes with Diverse Clinical Outcomes
Talkowski, M. E., Minikel, E. V., & Gusella, J. F. (2014) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000002 · Cited by 72 · see citing works
Rare inherited variation in autism: Beginning to see the forest and a few trees
Stein, J. L., Parikshak, N. N., & Geschwind, D. H. (2013) · Neuron · doi:10.1016/j.neuron.2013.01.010 · Cited by 68 · see citing works
Molecular subtyping and improved treatment of neurodevelopmental disease
Stessman, H. A. F., Turner, T. N., & Eichler, E. E. (2016) · Genome Medicine · doi:10.1186/s13073-016-0278-z · Cited by 25 · see citing works
Family-based genome-wide association study of autism spectrum disorder in middle eastern families
Al-Sarraj, Y., Al-Dous, E., Taha, R. Z., Ahram, D., Alshaban, F., Tolfat, M., El-Shanti, H., & Albagha, O. M. E. (2021) · Genes · doi:10.3390/genes12050761 · Cited by 17 · see citing works
- Authors
- Michaelson, J. J., Shi, Y., Gujral, M., Zheng, H., Malhotra, D., Jin, X., Jian, M., Liu, G., Greer, D., Bhandari, A., Wu, W., Corominas, R., Peoples, Á., Koren, A., Gore, A., Kang, S., Lin, G. N., Estabillo, J., Gadomski, T., Singh, B., Zhang, K., Akshoomoff, N., Corsello, C., McCarroll, S., Iakoucheva, L. M., Li, Y., Wang, J., & Sebat, J.
- Affiliations
- University of California San Diego (US)
- South China University of Technology (CN)
- BGI Group (China) (CN)
- National University of Defense Technology (CN)
- Trinity College Dublin (IE)
- Harvard University (US)
- Rady Children's Hospital-San Diego (US)
- University of Copenhagen (DK)
- Corresponding author
- Wang, Jun
- Sebat, Jonathan
- ORCID
- Michaelson, Jacob J.
- Shi, Yujian
- Gujral, Madhusudan
- Zheng, Hancheng
- Malhotra, Dheeraj
- Jin, Xin
- Liu, Guangming
- Bhandari, Abhishek
- Wu, Wenting
- Corominas, Roser
- Koren, Amnon
- Lin, Guan Ning
- Estabillo, Jasper
- Gadomski, Therese
- Singh, Balvindar
- Zhang, Kun
- Akshoomoff, Natacha
- Corsello, Christina
- McCarroll, Steven
- Iakoucheva, Lilia M.
- Li, Yingrui
- Wang, Jun
- Sebat, Jonathan
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 151
- Issue
- 7
- Pages
- 1431-1442
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3712641
- OpenAlex
- W2000391750
- Cited by
- 544
- References
- 62
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 26 · 2023: 23 · 2022: 26 · 2021: 28 · 2020: 42 · 2019: 40 · 2018: 50 · 2017: 52 · 2016: 59 · 2015: 64 · 2014: 58 · 2013: 48 · 2012: 1
- FWCI
- 27.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 385 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Simons Foundation
- National Institutes of Health
- National Institute of Mental Health (R01MH091350, MH076431, R01MH076431)
- National Human Genome Research Institute (HG005725, U01HG005725)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD065288)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- autism spectrum disorder, de novo germline mutation, hypermutability, mutational hotspots, copy number variation, monozygotic twins, compound heterozygosity, gene conversion, chromatin structure, mutation rate variation, ASD risk genes
- MeSH terms
- Animals, Autistic Disorder, Cell Line, Pan troglodytes, Exons, Female, Humans, Male, Maternal Age, Paternal Age, Twins, Monozygotic, Sequence Analysis, DNA, Germ-Line Mutation, Genome-Wide Association Study, Mutation Rate
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