ArticleAmerican journal of human genetics2010
Direct measure of the de novo mutation rate in autism and schizophrenia cohorts.
Article in American journal of human genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 3 of them syntheses that pooled it.
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Who cites it
138 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Meta-analysis of 46,000 germline de novo mutations linked to human inherited disease.Human genomics · 2024Pooled it
- Genetic variability in scaffolding proteins and risk for schizophrenia and autism-spectrum disorders: a systematic review.Journal of psychiatry & neuroscience : JPN · 2018Pooled it
- De novo mutation in schizophrenia.Schizophrenia bulletin · 2012Pooled it
- A phylogenetic estimate of canine retrotransposition rates based on genome assembly comparisons.Mobile DNA · 2026Article
- Mice carrying a GluN2B protein-truncating variant have altered NMDA receptor subunit composition and their behavior recapitulates patient phenotypes.Cellular and molecular life sciences : CMLS · 2026Article
- A phylogenetic estimate of canine retrotransposition rates based on genome assembly comparisons.bioRxiv : the preprint server for biology · 2025Article
- Unraveling the molecular landscape of congenital pseudoarthrosis of the tibia: insights from a comprehensive analysis of 159 probands.Orphanet journal of rare diseases · 2025Article
- Estimating mutation rate and characterising single nucleotide de novo mutations in pigs.Genetics, selection, evolution : GSE · 2025Article
- A structured coalescent model reveals deep ancestral structure shared by all modern humans.Nature genetics · 2025Article
- Assessment of mRNA Decay and Calculation of Codon Occurrence to mRNA Stability Correlation Coefficients after 5-EU Metabolic Labeling.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Characterization of Mice Carrying a Neurodevelopmental Disease-Associated GluN2B(L825V) Variant.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Accurate inference of population history in the presence of background selection.bioRxiv : the preprint server for biology · 2024Article
- UNC-116 and UNC-16 function with the NEKL-3 kinase to promote axon targeting.Development (Cambridge, England) · 2023Article
- Extensive variation in germline de novo mutations inGenome research · 2023Article
- Tetrahydrobiopterin: Beyond Its Traditional Role as a Cofactor.Antioxidants (Basel, Switzerland) · 2023Review
- Phasing of de novo mutations using a scaled-up multiple amplicon long-read sequencing approach.Human mutation · 2022Article
- Prefrontal circuits guiding social preference: Implications in autism spectrum disorder.Neuroscience and biobehavioral reviews · 2022Review
- FertilityOnline: A Straightforward Pipeline for Functional Gene Annotation and Disease Mutation Discovery.Genomics, proteomics & bioinformatics · 2022Article
- Exploration of Mutated Genes and Prediction of Potential Biomarkers for Childhood-Onset Schizophrenia Using an Integrated Bioinformatic Analysis.Frontiers in aging neuroscience · 2022Article
- Review
78 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
34 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of de novo mutations (DNMs) in common diseases remains largely unknown. Nonetheless, the rate of de novo deleterious mutations and the strength of selection against de novo mutations are critical to understanding the genetic architecture of a disease. Discovery of high-impact DNMs requires substantial high-resolution interrogation of partial or complete genomes of families via resequencing. We hypothesized that deleterious DNMs may play a role in cases of autism spectrum disorders (ASD) and schizophrenia (SCZ), two etiologically heterogeneous disorders with significantly reduced reproductive fitness. We present a direct measure of the de novo mutation rate (μ) and selective constraints from DNMs estimated from a deep resequencing data set generated from a large cohort of ASD and SCZ cases (n = 285) and population control individuals (n = 285) with available parental DNA. A survey of ∼430 Mb of DNA from 401 synapse-expressed genes across all cases and 25 Mb of DNA in controls found 28 candidate DNMs, 13 of which were cell line artifacts. Our calculated direct neutral mutation rate (1.36 × 10(-8)) is similar to previous indirect estimates, but we observed a significant excess of potentially deleterious DNMs in ASD and SCZ individuals. Our results emphasize the importance of DNMs as genetic mechanisms in ASD and SCZ and the limitations of using DNA from archived cell lines to identify functional variants.
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