Research by Topic: genetic

De novo mutations in regulatory elements in neurodevelopmental disorders

Published June 26, 2019 in nature

We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost […]

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Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder

Published June 26, 2019 in Science

Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments of transcriptomic organization in diseased brains are limited. In this work, we integrated genotypes and RNA sequencing in brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder, as well […]

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Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap

Published June 26, 2019 in Science

The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders-autism, schizophrenia, bipolar disorder, depression, and alcoholism-compared with matched controls. We identified patterns […]

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Paternally inherited cis-regulatory structural variants are associated with autism

Published June 26, 2019 in Science

The genetic basis of autism spectrum disorder (ASD) is known to consist of contributions from de novo mutations in variant-intolerant genes. We hypothesize that rare inherited structural variants in cis-regulatory elements (CRE-SVs) of these genes also contribute to ASD. We investigated this by assessing the evidence for natural selection and transmission distortion of CRE-SVs in […]

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Analysis of shared heritability in common disorders of the brain

Published June 26, 2019 in Science

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, […]

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Complete Disruption of Autism-Susceptibility Genes by Gene Editing Predominantly Reduces Functional Connectivity of Isogenic Human Neurons

Published June 26, 2019 in Stem Cell Reports

Autism spectrum disorder (ASD) is phenotypically and genetically heterogeneous. We present a CRISPR gene editing strategy to insert a protein tag and premature termination sites creating an induced pluripotent stem cell (iPSC) knockout resource for functional studies of ten ASD-relevant genes (AFF2/FMR2, ANOS1, ASTN2, ATRX, CACNA1C, CHD8, DLGAP2, KCNQ2, SCN2A, TENM1). Neurogenin 2 (NGN2)-directed induction […]

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AGENDA’s First Initiative is a Unified Registry of Family Data

Published October 17, 2018

Today, ASF announced that it will be leading the newly-launched Alliance for Genetic Etiologies of Neurodevelopmental Disorders and Autism (AGENDA). This alliance is a partnership of research and advocacy organizations focused on improving outcomes of individuals with all forms of autism by fostering a genetics-first approach to autism science. AGENDA will also work to strengthen […]

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Evidence of a second-hit model supports genetic and environmental roles in autism

Published January 24, 2016

This week in Science Reports, an article showed that the risk of autism is further increased in individuals with a specific mutation on chromosome 22 when another mutation is present.  One of these mutations is in a gene that is known to be affected by different environmental factors.  Scientists are using this data to help understand […]

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