The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
Open accessAbstract
It is well established that autism spectrum disorders (ASD) have a strong genetic component; however, for at least 70% of cases, the underlying genetic cause is unknown. Under the hypothesis that de novo mutations underlie a substantial fraction of the risk for developing ASD in families with no previous history of ASD or related phenotypes--so-called sporadic or simplex families--we sequenced all coding regions of the genome (the exome) for parent-child trios exhibiting sporadic ASD, including 189 new trios and 20 that were previously reported. Additionally, we also sequenced the exomes of 50 unaffected siblings corresponding to these new (n = 31) and previously reported trios (n = 19), for a total of 677 individual exomes from 209 families. Here we show that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD. Moreover, 39% (49 of 126) of the most severe or disruptive de novo mutations map to a highly interconnected β-catenin/chromatin remodelling protein network ranked significantly for autism candidate genes. In proband exomes, recurrent protein-altering mutations were observed in two genes: CHD8 and NTNG1. Mutation screening of six candidate genes in 1,703 ASD probands identified additional de novo, protein-altering mutations in GRIN2B, LAMC3 and SCN1A. Combined with copy number variant (CNV) data, these results indicate extreme locus heterogeneity but also provide a target for future discovery, diagnostics and therapeutics.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“including that, prima facie , most proteins encoded by ASD risk genes are involved either in synaptic structure and function or chromatin modification and regulation of gene expression 38,46,47,58 (Fig. 3).”
From Autism spectrum disorder (2020) · cites this paper as [38]
Experimental — accuracy not yet measuredIn the citing paper
“CNVs and SNPs have both been reported to play a major role in autism incidence (36–41).”
From Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms (2014) · cites this paper as [39]
In the citing paper
“An analysis of publicly released whole exome sequence data (Iossifov et al., 2012; O’Roak et al., 2012; Sanders et al., 2012) showed a modest trend towards an excess of biallelic, inherited, rare (MAF<1%), protein-altering variants in cases (8/612 ) compared to control siblings (2/419) (p=0.21, Fisher’s exact test, two-tailed) in at least one of the genes we screened (Table S5).”
From Using Whole-Exome Sequencing to Identify Inherited Causes of Autism (2013) · cites this paper as O’Roak et al., 2012
In the citing paper
“Hypomorphic, biallelic mutations, combined with CNVs and heterozygous stop mutations (Neale et al., 2012; O’Roak et al., 2012; Sanders et al., 2012) which completely inactivate one of two alleles, suggest that a common theme for ASD mutations in general might be partial loss of gene function and/or dosage sensitivity.”
From Using Whole-Exome Sequencing to Identify Inherited Causes of Autism (2013) · cites this paper as O’Roak et al., 2012
In the citing paper
“Together, results from these papers demonstrate a significant role for rare SNVs in genetic liability for ASD”
From Sex differences in autism spectrum disorders (2013) · cites this paper as [49]
In the citing paper
“Exome and whole-genome sequencing studies have estimated at least another ∼6% contribution to ASD7–10,15”
From Convergence of genes and cellular pathways dysregulated in autism spectrum disorders (2014) · cites this paper as [10]
In the citing paper
“and three other recent studies by Sanders et al.8, O’Roak et al.7 and Neale et al.23 (65 genes combined from all three; referred to as ‘SON-exomes’);”
From Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism (2014) · cites this paper as [7]
In the citing paper
“Various genetic approaches have been successful in identifying the causes of more than 1,000 Mendelian, and fewer non-Mendelian, forms of neurodevelopmental disorders: prototypical examples are intellectual disability62–68, autism spectrum disorder (ASD)69–77, epilepsy78,79 and schizophrenia80–82.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [71]
In the citing paper
“Genetic investigations in ASD have constructed seed-based networks with literature-curated PPIs to identify the convergence of ASD risk genes71,73.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [71]
In the citing paper
“This approach was applied to identify a highly interconnected PPI subnetwork among rare de novo variants in ASD71.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [71]
In the citing paper
“Many strong neurobiological candidates have emerged from the genes disrupted by de novo mutations in these studies, including mutations in previously identified ASD/ID genes.”
From A de novo convergence of autism genetics and molecular neuroscience (2014) · cites this paper as [24]
In the citing paper
“We note that the strongest effects are observed for de novo loss-of-function (or truncating) mutations”
From A de novo convergence of autism genetics and molecular neuroscience (2014) · cites this paper as [24]
In the citing paper
“Exome sequencing of ASD/ID families has revealed a significant excess of de novo mutations in probands when compared to unaffected siblings and has identified novel candidate genes contributing to the neurological deficits.”
From A de novo convergence of autism genetics and molecular neuroscience (2014) · cites this paper as [24]
In the citing paper
“New exome sequencing technology has identified novel rare variants and has found that sporadic cases of ASD/ID are enriched for disruptive de novo mutations.”
From A de novo convergence of autism genetics and molecular neuroscience (2014) · cites this paper as [24]
In the citing paper
“Another striking candidate is DYRK1A (dual-specificity tyrosine phosphorylation-regulated kinase 1A), for which three truncating mutations have been discovered in autism probands [24,44] and de novo structural variants in ID probands [54,55].”
From A de novo convergence of autism genetics and molecular neuroscience (2014) · cites this paper as [24]
In the citing paper
“In summary, only three genes [CHD8, SCN2A, and synaptic Ras GTPase activating protein 1 (SYNGAP1)] had two independent truncating de novo mutations in any single study, and no gene had more than three mutations.”
From A de novo convergence of autism genetics and molecular neuroscience (2014) · cites this paper as [24]
In the citing paper
“one de novo frameshift of ARID1B was found in a sporadic ASD case [24]”
From A de novo convergence of autism genetics and molecular neuroscience (2014) · cites this paper as [24]
In the citing paper
“In the case of paternal age, one mediating mechanism lies in the increased rate of de novo SNV and CNV with advancing paternal age (22,24,25,43,44).”
From Genetics and genomics of autism spectrum disorder: embracing complexity (2015) · cites this paper as [25]
In the citing paper
“TBR1 has been implicated in ASD (21,22,25,26) and ID (73).”
From Genetics and genomics of autism spectrum disorder: embracing complexity (2015) · cites this paper as [25]
In the citing paper
“Qualitatively, recent studies of rare variants also find it challenging to distinguish risk variation from the background stochastic noise (12–15).”
From Individual common variants exert weak effects on the risk for autism spectrum disorders (2012) · cites this paper as [13]
In the citing paper
“De novo loss of function mutations in this gene had previously been identified in two patients by WES2 and targeted resequencing16 of patients with ASD. In those studies however, causal relationship did not reach locus-specific significance.”
From A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP (2014) · cites this paper as [2]
In the citing paper
“Albeit rare, de novo mutations have emerged as substantial contributors to ASD risk [83, 165, 166, 254, 261, 309].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [261]
In the citing paper
“Chromodomain helicase DNA-binding protein 8 (CHD8), encoding a chromatin modifying gene on chromosome 14q11.2, is one of the high-penetrance ASD risk genes recently identified by sequencing studies [83, 165, 261, 347].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [261]
In the citing paper
“no truncating coding-sequence variation within SHANK1 and SHANK3”
From Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments (2014) · cites this paper as [36]
In the citing paper
“Recent exome sequencing studies only reported one de novo SHANK2 mutation out of 965 patients [32], [36], [37]”
From Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments (2014) · cites this paper as [36]
In the citing paper
“estimates from de novo exonic mutations (similar to those from SV data) suggest that ASD is highly polygenic (estimates ranged from 400–1000 genes). 84,85”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [85]
In the citing paper
“Three recent papers describe the results from exome sequencing of ~600 trios, and identify roles for de novo exonic mutations in SCN2A, KATNAL2, and CHD8 in the pathogenesis of ASD. 83–85”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [85]
In the citing paper
“Intriguingly, all three studies noted an increased rate of de novo exonic mutations in older parents (with the mutations generally being of paternal origin), 83–85”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [85]
In the citing paper
“However, a central finding from these papers was that only a minority of cases had a de novo putatively functional variant”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [85]
In the citing paper
“Unexpectedly, simplex and multiplex ASD pedigrees show relatively similar de novo mutation rates for SV 80,81 and exonic variation. 83–85”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [85]
In the citing paper
“Projections for ASD and SCZ suggest that variation at hundreds of different genes will ultimately be shown to be involved. 58,80,85”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [85]
In the citing paper
“The published results for ASD 83–85 and unpublished data on SCZ suggest these issues will be important and underscore the need for sequencing studies to have the same emphasis on statistical rigor and large sample sizes that has enabled GWAS to realize success for multiple psychiatric disorders. 154”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [85]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Mapping and quantifying mammalian transcriptomes by RNA-Seq
Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., & Wold, B. (2008) · Nature Methods · doi:10.1038/nmeth.1226 · Cited by 13,696
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 11,457
Warde-Farley, D., Donaldson, S. L., Comes, O., Zuberi, K., Badrawi, R., Chao, P., Franz, M., Grouios, C., Kazi, F., Lopes, C. T., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq537 · Cited by 4,835
Kessler, R. C., & Üstün, T. B. (2004) · International Journal of Methods in Psychiatric Research · doi:10.1002/mpr.168 · Cited by 4,771
Cytoscape 2.8: new features for data integration and network visualization
Smoot, M. E., Ono, K., Ruscheinski, J., Wang, P., & Ideker, T. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq675 · Cited by 4,770
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
Transcriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology
Voineagu, I., Wang, X., Johnston, P., Lowe, J. K., Tian, Y., Horvath, S., Mill, J., Cantor, R. M., Blencowe, B. J., & Geschwind, D. H. (2011) · Nature · doi:10.1038/nature10110 · Cited by 1,874
Computing topological parameters of biological networks
Assenov, Y., Ramírez, F., Schelhorn, S.-E., Lengauer, T., & Albrecht, M. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm554 · Cited by 1,805
Estimating the Number of Classes via Sample Coverage
Chao, A., & Lee, S. (1992) · Journal of the American Statistical Association · doi:10.1080/01621459.1992.10475194 · Cited by 1,472
Cited by
Sorted by citations
Items 501–600 of 1,011
Nesprins in health and disease
Cartwright, S., & Karakesisoglou, I. (2013) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2013.12.010 · Cited by 79
Cav1.3 (CACNA1D) L‐type Ca2+ channel dysfunction in CNS disorders
Pinggera, A., & Striessnig, J. (2016) · The Journal of Physiology · doi:10.1113/jp270672 · Cited by 81
“Mutations G407R (exon 8a), A749G and V584I were identified in the affected individuals but absent in parents or unaffected siblings and therefore classified as de novo (Iossifov et al. 2012; O’Roak et al. 2012; De Rubeis et al. 2014).”
Lalli, M. A., Jang, J., Park, J.-H. C., Wang, Y., Guzman, E., Zhou, H., Audouard, M., Bridges, D. C., Tovar, K. R., Papuc, S. M., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw010 · Cited by 79
Interpreting the role of de novo protein-coding mutations in neuropsychiatric disease
Gratten, J., Visscher, P. M., Mowry, B. J., & Wray, N. R. (2013) · Nature Genetics · doi:10.1038/ng.2555 · Cited by 77
Rossignol, D. A., & Frye, R. E. (2014) · Frontiers in Pediatrics · doi:10.3389/fped.2014.00087 · Cited by 79
Whole-genome sequencing in an autism multiplex family
Shi, L., Zhang, X., Golhar, R., Otieno, F. G., He, M., Hou, C., Kim, C., Keating, B. J., Lyon, G. J., Wang, K., et al. (2013) · Molecular Autism · doi:10.1186/2040-2392-4-8 · Cited by 82
“In summary, our study represents one of the first examples demonstrating the feasibility of whole genome sequencing for familial samples and analyzing inherited mutations on ASDs.”
BackgroundInfluentialIdiopathic Autism: Cellular and Molecular Phenotypes in Pluripotent Stem Cell-Derived Neurons
Liu, X., Campanac, E., Cheung, H., Ziats, M. N., Canterel-Thouennon, L., Raygada, M. J., Baxendale, V., Pang, A. L., Yang, L., Swedo, S. E., et al. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9961-8 · Cited by 83
“CTNNB1, also known as βcatenin, have recently been identified as one of the top de novo ASD risk contributing mutations [48].”
BackgroundGenetic architecture of autism spectrum disorder: Lessons from large-scale genomic studies
Choi, L., & An, J. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.06.028 · Cited by 81
“This is unlikely as the human genome contains very few DNVs (1 in 20 individuals) (O’Roak et al., 2012; Sanders et al., 2012).”
How next-generation sequencing is transforming complex disease genetics
Kilpinen, H., & Barrett, J. C. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.10.001 · Cited by 81
Aras, L. M., Isla, J., & Mingorance, A. (2015) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2014.12.028 · Cited by 80
“This is an open access article under to causemilder forms of epilepsy, migraine, and autismwithout epilepsy [8–10].”
Deletion of CTNNB1 in inhibitory circuitry contributes to autism-associated behavioral defects
Dong, F., Jiang, J. H., McSweeney, C., Zou, D., Liu, L., & Mao, Y. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw131 · Cited by 84
“Consistently, mutations of CTNNB1 were identified in patients with ASD (6) and ID (9).”
BackgroundInfluentialDe novo variants in SETD1B are associated with intellectual disability, epilepsy and autism
Hiraide, T., Nakashima, M., Yamoto, K., Fukuda, T., Kato, M., Ikeda, H., Sugie, Y., Aoto, K., Kaname, T., Nakabayashi, K., et al. (2018) · Human Genetics · doi:10.1007/s00439-017-1863-y · Cited by 75
Perturbed proteostasis in autism spectrum disorders
Louros, S. R., & Osterweil, E. K. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13723 · Cited by 89
Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation
Durán, D., Zeng, X. Q., Jin, S. C., Choi, J., Nelson-Williams, C. J., Yatsula, B. A., Gaillard, J. R., Furey, C. G., Lu, Q., Timberlake, A. T., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.11.041 · Cited by 78
CTNNB1 in neurodevelopmental disorders
Zhuang, W., Ye, T., Wang, W., Song, W., & Tan, T. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1143328 · Cited by 86
“(51) Case–control De novo mutation 677 ASD”
BackgroundMethodPrenatal Neurogenesis in Autism Spectrum Disorders
Kaushik, G., & Zarbalis, K. S. (2016) · Frontiers in Chemistry · doi:10.3389/fchem.2016.00012 · Cited by 80
Mercati, O., Huguet, G., Danckaert, A., André-Leroux, G., Maruani, A., Bellinzoni, M., Rolland, T., Gouder, L., Mathieu, A., Buratti, J., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.61 · Cited by 87
Sajan, S. A., Jhangiani, S. N., Muzny, D. M., Gibbs, R. A., Lupski, J. R., Glaze, D. G., Kaufmann, W. E., Skinner, S. A., Annese, F., Friez, M. J., et al. (2016) · Genetics in Medicine · doi:10.1038/gim.2016.42 · Cited by 81
The role of cadherin genes in five major psychiatric disorders: A literature update
Hawi, Z., Tong, J., Dark, C., Yates, H., Johnson, B. P., & Bellgrove, M. A. (2017) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32592 · Cited by 80
“Further, full exome sequencing of non-familial ASD (O’Roak et al., 2012) revealed that among 62 top deleterious de novo mutations identified as contributing to ASD risk, two were mapped to CDH5 and the protocadherin PCDHB4.”
BackgroundWang, W., Corominas, R., & Lin, G. N. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00258 · Cited by 70
“…a powerful resource, together with other information, to complement genetic data such as DNMs to elucidate causal molecular drivers of cellular, circuit level, and brain-wide alterations in pathology (Bergholdt et al., 2007; Lage et al., 2008; Neale et al., 2012; O’Roak et al., 2012b) (Figure 1D).”
BackgroundMethodAn, J., Cristino, A. S., Zhao, Q., Edson, J., Williams, S. M., Ravine, D., Wray, J. A., Marshall, V. M., Hunt, A., Whitehouse, A., et al. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.38 · Cited by 81
Zhao, N., Han, J. G., Shyu, C., & Korkin, D. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003592 · Cited by 81
Berto, S., Usui, N., Konopka, G., & Fogel, B. L. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw110 · Cited by 80
“Among the ELAVL2 alternatively spliced events, we found CADM1, a synaptic cell adhesion molecule associated with ASD (73–76), CTNNB1, a neuronal development gene involved in ASD and FMRP-regulated pathways (31,61,77) and UBE3A, a gene important for dendritic patterning and associated with ASD (78–81) (Supplementary Ma…”
BackgroundThe Role of PTEN in Neurodevelopment
Skelton, P. D., Stan, R. V., & Luikart, B. W. (2019) · Complex Psychiatry · doi:10.1159/000504782 · Cited by 82
Overview of Mouse Models of Autism Spectrum Disorders
Bey, A. L., & Jiang, Y. (2014) · Current Protocols in Pharmacology · doi:10.1002/0471141755.ph0566s66 · Cited by 85
Dang, T., Duan, W. Y., Yu, B., Tong, D. L., Cheng, C., Zhang, Y. F., Wu, W., Ye, K., Zhang, W. X., Wu, M., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.253 · Cited by 80
Recent Advances in the Genetics of Autism Spectrum Disorder
Rubeis, S. D., & Buxbaum, J. D. (2015) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-015-0553-1 · Cited by 77
Williams, S. M., An, J., Edson, J., Watts, M. E., Murigneux, V., Whitehouse, A., Jackson, C. J., Bellgrove, M. A., Cristino, A. S., & Claudianos, C. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0049-x · Cited by 77
Balemans, M. C. M., Kasri, N. N., Kopanitsa, M. V., Afinowi, N. O., Ramakers, G. J. A., Peters, T. A., Beynon, A. J., Janssen, S. M., van Summeren, R. C. J., Eeftens, J. M., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds490 · Cited by 78
Arid1b Haploinsufficiency Causes Abnormal Brain Gene Expression and Autism-Related Behaviors in Mice
Shibutani, M., Horii, T., Shoji, H., Morita, S., Kimura, M., Terawaki, N., Miyakawa, T., & Hatada, I. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18091872 · Cited by 72
Rapanelli, M., Tan, T., Wang, W., Wang, X., Wang, Z.-J., Zhong, P., Frick, L., Qin, L., Ma, K., Qu, J., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-019-0498-x · Cited by 74
TBR1 regulates autism risk genes in the developing neocortex
Notwell, J. H., Heavner, W. E., Darbandi, S. F., Katzman, S., McKenna, W. L., Ortiz-Londono, C. F., Tastad, D., Eckler, M. J., Rubenstein, J. L. R., McConnell, S. K., et al. (2016) · Genome Research · doi:10.1101/gr.203612.115 · Cited by 74
“(Iossifov et al. 2012; Kong et al. 2012; Neale et al. 2012; O’Roak et al. 2012), with an additional 56 quartets from the Simons Simplex collection (Willsey et al.”
BackgroundMethodResultBrain Transcriptome Databases: A User's Guide
Keil, J. M., Qalieh, A., & Kwan, K. Y. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1930-17.2018 · Cited by 79
Culotta, L., & Penzes, P. (2020) · Molecular Autism · doi:10.1186/s13229-020-00339-0 · Cited by 83
Rea, V., & Raay, T. J. V. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.575575 · Cited by 77
Increased burden ofde novopredicted deleterious variants in complex congenital diaphragmatic hernia
Yu, L., Sawle, A., Wynn, J., Aspelund, G., Stolar, C. J. H., Arkovitz, M. S., Potoka, D. A., Azarow, K. S., Mychaliska, G. B., Shen, Y., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv196 · Cited by 77
Autism genes keep turning up chromatin
LaSalle, J. M. (2013) · OA Autism · doi:10.13172/2052-7810-1-2-610 · Cited by 79
Genome-wide analysis of differential RNA editing in epilepsyPreprint
Srivastava, P. K., Bagnati, M., Delahaye‐Duriez, A., Ko, J., Rotival, M., Langley, S. R., Shkura, K., Mazzuferi, M., Danis, B., van Eyll, J. M., et al. (2017) · Genome Research · doi:10.1101/gr.210740.116 · Cited by 79
“…RE is an enzyme-catalyzed event and the responsible enzymes tend to edit nucleotides in a cluster, especially in the 3′ UTR or introns of the gene (Park et al. 2012), we reasoned that, potentially, an isolated RNA-edited site ismore likely to be a false-positive prediction than two or more…”
BackgroundResultInfluentialHe, Z., O’Roak, B. J., Smith, J. D., Wang, G., Hooker, S. E., Santos‐Cortez, R. L. P., Li, B., Kan, M., Krumm, N., Nickerson, D. A., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.11.021 · Cited by 75
“Previously, 189 of these trios were analyzed to detect de novo events.(25) An additional 10 trios, which have not been described, were also analyzed.”
BackgroundMethodInfluentialSelf-citationThe novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders
Ang, C. E., Ma, Q., Wapinski, O. L., Fan, S., Flynn, R. A., Lee, Q. Y., Coe, B. P., Onoguchi, M., Olmos, V. H., Do, B. T., et al. (2019) · eLife · doi:10.7554/elife.41770 · Cited by 76
Self-citationPaternal age affects offspring via an epigenetic mechanism involving REST/NRSF
Yoshizaki, K., Kimura, R., Kobayashi, H., Oki, S., Kikkawa, T., Mai, L., Koike, K., Mochizuki, K., Inada, H., Matsui, Y., et al. (2021) · EMBO Reports · doi:10.15252/embr.202051524 · Cited by 91
Next-Generation sequencing transforming clinical practice and precision medicine
Yadav, D., Patil‐Takbhate, B., Khandagale, A. S., Bhawalkar, J., Tripathy, S. P., & Khopkar-Kale, P. (2023) · Clinica Chimica Acta · doi:10.1016/j.cca.2023.117568 · Cited by 79
Mottron, L., Belleville, S., Rouleau, G. A., & Collignon, O. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.07.012 · Cited by 85
Kabir, Z. D., Lee, A. S., & Rajadhyaksha, A. M. (2016) · The Journal of Physiology · doi:10.1113/jp270673 · Cited by 77
PTEN: Local and Global Modulation of Neuronal Function in Health and Disease
Knafo, S., & Esteban, J. A. (2017) · Trends in Neurosciences · doi:10.1016/j.tins.2016.11.008 · Cited by 79
Synaptic Wnt/GSK3βSignaling Hub in Autism
Caracci, M. O., Ávila, M. E., & Ferrari, G. V. D. (2016) · Neural Plasticity · doi:10.1155/2016/9603751 · Cited by 78
“More recently, the chromo-helicase domain protein 8 (CHD8) [13, 14, 32], which inhibits β-catenin through direct binding [33], and DYRK1A that modulates Wnt signaling through interaction with the p120 catenin [34] have been found to be associated with ASDs.”
BackgroundWalking on multiple disease-gene networks to prioritize candidate genes
Jiang, R. (2015) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjv008 · Cited by 75
“From the literature (PMID 22495309) (O'Roak et al., 2012), we collected 153 unique candidate genes that contained 154 unique de novo mutations, and 34 of these genes were reported as likely functional in the literature.”
BackgroundGreenwood, T. A., Lazzeroni, L. C., Calkins, M. E., Freedman, R., Green, M. F., Gur, R. E., Gur, R. C., Light, G. A., Nuechterlein, K. H., D, A. O. M., et al. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.11.008 · Cited by 79
“…CTNNA2, DBH, DISC1, DLGAP2, GRID2, GRIN2B, HTR2A, RELN, and SLC6A3 in schizophrenia and related disorders (de Ligt et al., 2012; Fromer et al., 2014; Guilmatre et al., 2009; Iossifov et al., 2012; Li et al., 2014; Neale et al., 2012; O'Roak et al., 2012; Rauch et al., 2012; Sanders et al., 2012).”
Rapid Method for the Isolation of Mammalian Sperm DNA
Wu, H., de Gannes, M., Luchetti, G., & Pilsner, J. R. (2015) · BioTechniques · doi:10.2144/000114280 · Cited by 75
Chen, S., Fragoza, R., Klei, L., Liu, Y., Wang, J., Roeder, K., Devlin, B., & Yu, H. (2018) · Nature Genetics · doi:10.1038/s41588-018-0130-z · Cited by 75
Damaging de novo mutations diminish motor skills in children on the autism spectrum
Buja, A., Volfovsky, N., Krieger, A. M., Lord, C., Lash, A. E., Wigler, M., & Iossifov, I. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1715427115 · Cited by 64
“In an earlier effort, we and others have shown that ASD individuals with low nonverbal IQ (nvIQ) have a significantly increased incidence of damaging de novo mutations (2, 13).”
BackgroundGoodwin, L. R., & Picketts, D. J. (2017) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2017.10.008 · Cited by 76
“…et al., 2013; O'Roak et al., 2014) CHD7 CHD7 CHARGE syndrome (Lalani et al., 2006; Vissers et al., 2004) CHD8 CHD8 ASD (Bernier et al., 2014; O'Roak et al., 2012) ISWI SMARCA1 SNF2L Coffin-Siris syndrome-like phenotype (Karaca et al., 2015) SMARCA1 SNF2L Rett syndrome-like phenotype (Lopes…”
InfluentialAge‐associated alterations in the somatic mutation and DNA methylation levels in plants
Dubrovina, A. S., & Kiselev, K. V. (2015) · Plant Biology · doi:10.1111/plb.12375 · Cited by 73
Nava, C., Keren, B., Mignot, C., Rastetter, A., Chantot‐Bastaraud, S., Faudet, A., Fonteneau, E., Amiet, C., Laurent‐Levinson, C., Jacquette, A., et al. (2013) · European Journal of Human Genetics · doi:10.1038/ejhg.2013.88 · Cited by 75
Characterizing autism spectrum disorders by key biochemical pathways
Subramanian, M. P., Timmerman, C., Schwartz, J. L., Pham, D. L., & Meffert, M. K. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00313 · Cited by 71
A specific mutation in TBL1XR1 causes Pierpont syndrome
Heinen, C. A., Jongejan, A., Watson, P. J., Redeker, B., Boelen, A., Boudzovitch-Surovtseva, O., Forzano, F., Hordijk, R., Kelley, R., Olney, A. H., et al. (2016) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2015-103233 · Cited by 73
Cappi, C., Brentani, H., Lima, L., Sanders, S. J., Zai, G., Diniz, B. J., Reis, V. N. S., Hounie, A. G., Conceição do Rosário, M., Mariani, D., et al. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.30 · Cited by 71
Autism 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
“Fourth, genes that contribute to ASD represent diverse biological pathways and include not only participants in synaptic function(21,42) but also genes involved in global regulation of transcript expression and epigenetic modification.(18,19,26,43) Finally, many genes associated with ASD confer shared risk to a wide r…”
BackgroundMcDiarmid, T. A., Belmadani, M., Liang, J., Meili, F., Mathews, E., Mullen, G. P., Hendi, A., Wong, W.-R., Rand, J. B., Mizumoto, K., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1912049116 · Cited by 69
Zhang, K., Fang, Y., Zhu, J. K., Han, S., Chen, J., Wu, X., Chen, Y., Shen, T., Liao, J., Guo, W., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.085 · Cited by 70
AKAPs integrate genetic findings for autism spectrum disorders
Poelmans, G., Franke, B., Pauls, D. L., Glennon, J. C., & Buitelaar, J. K. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.48 · Cited by 76
Mutations in ASH1L confer susceptibility to Tourette syndrome
Liu, S., Tian, M., He, F., Li, J., Xie, H. B., Liu, W., Zhang, Y., Zhang, R., Yi, M., Che, F., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0560-8 · Cited by 73
Biomarkers for Psychiatric Disorders: Where Are We Standing?
Martins‐de‐Souza, D. (2013) · Disease Markers · doi:10.1155/2013/321071 · Cited by 78
Steinberg, J., & Webber, C. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.09.013 · Cited by 71
Liao, X., & Li, Y. (2020) · Molecular Brain · doi:10.1186/s13041-020-00634-0 · Cited by 73
A Likelihood-Based Framework for Variant Calling and De Novo Mutation Detection in Families
Li, B., Chen, W., Zhan, X., Busonero, F., Sanna, S., Sidore, C., Cucca, F., Kang, H. M., & Abecasis, G. R. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002944 · Cited by 73
“We called a candidate de novo event only in places where the parents were called as homozygotes for the reference allele, and the offspring was called as heterozygote [18–20] – a strategy that removes most alignment artifacts.”
BackgroundInfluentialFang, L., Sahana, G., Ma, P., Su, G., Yu, Y., Zhang, S., Lund, M. S., & Sørensen, P. B. (2017) · Genetics Selection Evolution · doi:10.1186/s12711-017-0319-0 · Cited by 72
“However, genomic markers that are associated with a complex trait may not be uniformly and randomly distributed over the genome, but rather be clustered in genes that are part of interconnected biological pathways and networks [2, 11, 12].”
BackgroundKatrancha, S. M., Wu, Y., Zhu, M., Eipper, B. A., Koleske, A. J., & Mains, R. E. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx355 · Cited by 68
Nguyen, R. L., Medvedeva, Y. V., Ayyagari, T., Schmunk, G., & Gargus, J. J. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.08.003 · Cited by 71
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
Mutations in ARID2 are associated with intellectual disabilities
Shang, L., Cho, M. T., Retterer, K., Folk, L., Humberson, J. B., Rohena, L. O., Sidhu, A., Saliganan, S., Iglesias, A. D., Vitazka, P., et al. (2015) · Neurogenetics · doi:10.1007/s10048-015-0454-0 · Cited by 70
“Haploinsufficiency of ARID1B has been identified as a frequent cause of intellectual disability, agenesis of the corpus callosum [12, 13], and autism [14, 15]; and mutations in ARID1A and ARID1B cause Coffin-Siris syndrome [16, 17].”
BackgroundUzunova, G., Hollander, E., & Shepherd, J. D. (2014) · Current Neuropharmacology · doi:10.2174/1570159x113116660046 · Cited by 73
“Genetic factors are important in the etiology of ASDs with monozygotic twins exhibiting a very high concordance rate [17].”
InfluentialWang, Q., Shashikant, C. S., Jensen, M., Altman, N., & Girirajan, S. (2017) · Scientific Reports · doi:10.1038/s41598-017-01005-x · Cited by 77
Self-citationSelected vitamin D metabolic gene variants and risk for Autism Spectrum Disorder in the charge study
Schmidt, R. J., Hansen, R. L., Hartiala, J., Allayee, H., Sconberg, J. L., Schmidt, L. C., Volk, H. E., & Tassone, F. (2015) · Early Human Development · doi:10.1016/j.earlhumdev.2015.05.008 · Cited by 68
“Interestingly, recent work suggests that de novo genetic variation contributes greatly to the development of ASD [38] and that in sporadic (non-familial) cases of autism, de novo point mutations in protein-coding regions are overwhelmingly paternal in origin with a 4:1 paternal bias [39].”
BackgroundDincer, A., Gavin, D. P., Xu, K., Zhang, B., Dudley, J. T., Schadt, E. E., & Akbarian, S. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.169 · Cited by 65
The Mechanisms of CHD8 in Neurodevelopment and Autism Spectrum Disorders
Weissberg, O., & Elliott, E. (2021) · Genes · doi:10.3390/genes12081133 · Cited by 72
“Chromodomain-helicase-DNA-binding protein 8 (CHD8) was first linked to ASD about a decade ago, when de novo mutations were first identified in two ASD children (Table S1) [21].”
BackgroundVoineagu, I., & Eapen, V. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00738 · Cited by 74
“Four recent studies undertook exome-sequencing in several hundreds of parent-child trios in order to identify de novo single nucleotide variants (SNVs) and copy number variants (CNVs) associated with the disease (Iossifov et al., 2012; Neale et al., 2012; O’Roak et al., 2012; Sanders et al., 2012).”
BackgroundAdvances in Dyslexia Genetics—New Insights Into the Role of Brain Asymmetries
Paracchini, S., Diaz, R., & Stein, J. F. (2016) · Advances in genetics · doi:10.1016/bs.adgen.2016.08.003 · Cited by 72
The Role of De Novo Noncoding Regulatory Mutations in Neurodevelopmental Disorders
Turner, T. N., & Eichler, E. E. (2018) · Trends in Neurosciences · doi:10.1016/j.tins.2018.11.002 · Cited by 74
Self-citationThe Use of Next-Generation Sequencing for Research and Diagnostics for Intellectual DisabilityPreprint
Harripaul, R., Noor, A., Ayub, M., & Vincent, J. B. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026864 · Cited by 72
“Recently, many software programs have been developed to accurately detect CNVs and other structural variations such as CONIFER (Krumm et al. 2012; O’Roak et al. 2012) and XHMM (Fromer et al.”
MethodSchizophrenia Related Variants in CACNA1C also Confer Risk of Autism
Li, J., Zhao, L., You, Y., Lu, T., Jia, M., Yu, H., Ruan, Y., Yue, W., Liu, J., Lu, L., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133247 · Cited by 73
“The susceptibility genes (such as DISC1 [33,34], RELN [35,36], GABA [37–39], SHANK3 [40,41], NRXN1 [20,42], NTNG1 [43,44], etc.), which were associated with schizophrenia, also confer risk to ASD.”
The role of Pax6 in brain development and its impact on pathogenesis of autism spectrum disorder
Kikkawa, T., Casingal, C. R., Chun, S. H., Shinohara, H. M., Hiraoka, K., & Osumi, N. (2018) · Brain Research · doi:10.1016/j.brainres.2018.02.041 · Cited by 67
Murtaza, N., Cheng, A. A., Brown, C. O., Meka, D. P., Hong, S., Uy, J. A., El-Hajjar, J., Pipko, N., Unda, B. K., Schwanke, B., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111678 · Cited by 70
Micucci, J. A., Layman, W. S., Hurd, E. A., Sperry, E. D., Frank, S. F., Durham, M. A., Swiderski, D. L., Skidmore, J. M., Scacheri, P. C., Raphael, Y., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt435 · Cited by 68
“CHD7 has been shown to regulate neurogenesis in the adult dentate gyrus of the hippocampus (24) and is also implicated in autism spectrum disorder (48).”
BackgroundYin, J., & Schaaf, C. P. (2016) · Prenatal Diagnosis · doi:10.1002/pd.4942 · Cited by 78
“DYRK1A The dual-specificity tyrosine-regulated kinase DYRK1A lies within the Down syndrome critical region,(219) and recurrent loss-of-function mutations in DYRK1A have been reported in multiple individuals on the autism spectrum.(33,39,108,129,220)”
BackgroundLinking Cell Polarity to Cortical Development and Malformations
Hakanen, J., Ruiz-Reig, N., & Tissir, F. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00244 · Cited by 69
Genetic heterogeneity in autism: From single gene to a pathway perspective
An, J., & Claudianos, C. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.06.013 · Cited by 68
De novo CACAN1D Ca2+ channelopathies: clinical phenotypes and molecular mechanism
Ortner, N. J., Kaserer, T., Copeland, J. N., & Striessnig, J. (2020) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-020-02418-w · Cited by 68
Disruption of MBD5 contributes to a spectrum of psychopathology and neurodevelopmental abnormalities
Hodge, J. C., Mitchell, E. L. D., Pillalamarri, V., Toler, T. L., Bartel, F., Kearney, H. M., Zou, Y. S., Tan, W., Hanscom, C., Kirmani, S., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.42 · Cited by 67
Silfhout, A. T. V., Rajamanickam, S., Jensik, P. J., Vergult, S., Rocker, N. D., Newhall, K. J., Raghavan, R., Reardon, S., Jarrett, K. E., McIntyre, T., et al. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.03.013 · Cited by 70
Self-citationPaternal lifestyle as a potential source of germline mutations transmitted to offspring
Linschooten, J. O., Verhofstad, N., Gützkow, K. B., Olsen, A.-K. H., Yauk, C. L., Oligschlaeger, Y., Brunborg, G., van Schooten, F., & Godschalk, R. (2013) · The FASEB Journal · doi:10.1096/fj.13-227694 · Cited by 68
Evidence for differential alternative splicing in blood of young boys with autism spectrum disorders
Stamova, B. S., Tian, Y., Nordahl, C. W., Shen, M. D., Rogers, S. J., Amaral, D. G., & Sharp, F. R. (2013) · Molecular Autism · doi:10.1186/2040-2392-4-30 · Cited by 70
“This gene also regulates the beta catenin Wnt signaling pathway which has also been implicated in ASD [97,107].”
BackgroundResultOxytocin: Parallel Processing in the Social Brain?
Dölen, G. (2015) · Journal of Neuroendocrinology · doi:10.1111/jne.12284 · Cited by 65
Brain-specific functional relationship networks inform autism spectrum disorder gene prediction
Duda, M., Zhang, H., Li, H., Wall, D. P., Burmeister, M., & Guan, Y. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0098-6 · Cited by 65
The role of genetics and genomics in clinical psychiatry
Hoehe, M. R., & Morris-Rosendahl, D. J. (2018) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2018.20.3/mhoehe · Cited by 69
Atypical Neurogenesis in Induced Pluripotent Stem Cells From Autistic Individuals
Adhya, D., Swarup, V., Nagy, R., Polit, L. D., Shum, C., Valencia-Alarcón, E. P., Jozwik, K. M., Méndez, M. A., Horder, J., Loth, E., et al. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.06.014 · Cited by 65
De novo mutations, genetic mosaicism and human disease
Mohiuddin, M., Kooy, R. F., & Pearson, C. E. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.983668 · Cited by 69
Durak, O., de Anda, F. C., Singh, K. K., Leussis, M. P., Petryshen, T. L., Sklar, P. B., & Tsai, L.-H. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.42 · Cited by 70
A Potential Contributory Role for Ciliary Dysfunction in the 16p11.2 600 kb BP4-BP5 Pathology
Migliavacca, E., Golzio, C., Männik, K., Blumenthal, I., Oh, E. C. T., Harewood, L., Kosmicki, J. A., Loviglio, M. N., Giannuzzi, G., Hippolyte, L., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.04.002 · Cited by 62
“Other genes whose products participate in proteasomal function have been implicated in ASDs, including CUL3 (MIM: 603136) 74,75 and UBE3A .”
Co-expression Profiling of Autism Genes in the Mouse Brain
Menashe, I., Grange, P., Larsen, E. C., Banerjee‐Basu, S., & Mitra, P. P. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003128 · Cited by 68
“Recent genomic advances have led to the discovery of diverse genetic loci linked to ASD, including chromosomal aberrations [15,16], copy number variations [11,17,18] and both common and rare single nucleotide variations (SNVs) [19–24].”
Background
Metadata
- Authors
- O’Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., Turner, E. H., Stanaway, I. B., Vernot, B., Malig, M., Baker, C., Reilly, B., Akey, J. M., Borenstein, E., Rieder, M. J., Nickerson, D. A., Bernier, R., Shendure, J., & Eichler, E. E.
- Affiliations
- University of Washington (US)
- Santa Fe Institute (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Shendure, Jay
- Eichler, Evan E.
- ORCID
- Venue
- Nature
- Published
- 2012-04-04
- Volume
- 485
- Issue
- 7397
- Pages
- 246-250
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3350576
- OpenAlex
- W1964444099
- Cited by
- 2,165
- References
- 50
- Citations by year
- 2026: 42 · 2025: 68 · 2024: 85 · 2023: 101 · 2022: 104 · 2021: 137 · 2020: 151 · 2019: 147 · 2018: 143 · 2017: 173 · 2016: 198 · 2015: 219 · 2014: 262 · 2013: 212 · 2012: 118
- FWCI
- 131.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Simons Foundation
- University of Washington
- Simons Foundation Autism Research Initiative (137578)
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL-102924, RC2HL102926, RC2HL102923, UC2HL102924, HL 1029230, R01HL094976, HL094976, RC2HL102924, UC2HL102926, HL-102926)
- National Human Genome Research Institute
- National Institute of Environmental Health Sciences (HHSN273200800010C)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD065285, R01HD065285)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- de novo mutations, paternal age, protein-protein interaction network, β-catenin signaling, chromatin remodeling, CHD8, SCN2A, NTNG1, locus heterogeneity, simplex families, autism risk genes, parent-child trios, unaffected siblings, recurrent mutations, p53 pathway, copy number variation
- MeSH terms
- Netrins, Autistic Disorder, DNA-Binding Proteins, Exons, Humans, Laminin, Nerve Tissue Proteins, Parents, Stochastic Processes, Transcription Factors, Reproducibility of Results, Sodium Channels, Signal Transduction, Tumor Suppressor Protein p53, Receptors, N-Methyl-D-Aspartate, Point Mutation, Genetic Predisposition to Disease, Siblings, beta Catenin, GPI-Linked Proteins, Exome, Protein Interaction Maps, NAV1.1 Voltage-Gated Sodium Channel
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
