Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism

Cell, Год журнала: 2020, Номер 180(3), С. 568 - 584.e23

Опубликована: Янв. 23, 2020

Язык: Английский

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The genetic architecture of the human cerebral cortex

Science, Год журнала: 2020, Номер 367(6484)

Опубликована: Март 19, 2020

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify variants affect structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed surface area and average thickness whole 34 regions with functional specializations. identified 199 significant found enrichment for influencing total within regulatory elements are active during prenatal development, supporting radial unit hypothesis. Loci regional cluster near genes in Wnt signaling pathways, which progenitor expansion areal identity. Variation structure genetically correlated function, Parkinson's disease, insomnia, depression, neuroticism, attention deficit hyperactivity disorder.

Язык: Английский

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Defining the Genetic, Genomic, Cellular, and Diagnostic Architectures of Psychiatric Disorders

Cell, Год журнала: 2019, Номер 177(1), С. 162 - 183

Опубликована: Март 1, 2019

Язык: Английский

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Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks

Cell, Год журнала: 2019, Номер 178(4), С. 850 - 866.e26

Опубликована: Авг. 1, 2019

Язык: Английский

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Rare coding variation provides insight into the genetic architecture and phenotypic context of autism

Nature Genetics, Год журнала: 2022, Номер 54(9), С. 1320 - 1331

Опубликована: Авг. 18, 2022

Язык: Английский

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A human cell atlas of fetal chromatin accessibility

Science, Год журнала: 2020, Номер 370(6518)

Опубликована: Ноя. 13, 2020

The genomics of human development Understanding the trajectory a developing requires an understanding how genes are regulated and expressed. Two papers now present pooled approach using three levels combinatorial indexing to examine single-cell gene expression chromatin landscapes from 15 organs in fetal samples. Cao et al. focus on measurements RNA broadly distributed cell types provide insights into organ specificity. Domcke examined accessibility cells these identify regulatory elements that regulate expression. Together, analyses generate comprehensive atlases early development. Science , this issue p. eaba7721 eaba7612

Язык: Английский

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Chromatin and gene-regulatory dynamics of the developing human cerebral cortex at single-cell resolution

Cell, Год журнала: 2021, Номер 184(19), С. 5053 - 5069.e23

Опубликована: Авг. 13, 2021

Язык: Английский

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Maturation and circuit integration of transplanted human cortical organoids

Nature, Год журнала: 2022, Номер 610(7931), С. 319 - 326

Опубликована: Окт. 12, 2022

Abstract Self-organizing neural organoids represent a promising in vitro platform with which to model human development and disease 1–5 . However, lack the connectivity that exists vivo, limits maturation makes integration other circuits control behaviour impossible. Here we show stem cell-derived cortical transplanted into somatosensory cortex of newborn athymic rats develop mature cell types integrate sensory motivation-related circuits. MRI reveals post-transplantation organoid growth across multiple lines animals, whereas single-nucleus profiling shows progression corticogenesis emergence activity-dependent transcriptional programs. Indeed, neurons display more complex morphological, synaptic intrinsic membrane properties than their counterparts, enables discovery defects derived from individuals Timothy syndrome. Anatomical functional tracings receive thalamocortical corticocortical inputs, vivo recordings activity demonstrate these inputs can produce responses cells. Finally, extend axons throughout rat brain optogenetic activation drive reward-seeking behaviour. Thus, engage host We anticipate this approach will be useful for detecting circuit-level phenotypes patient-derived cells cannot otherwise uncovered.

Язык: Английский

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Long-term maturation of human cortical organoids matches key early postnatal transitions

Nature Neuroscience, Год журнала: 2021, Номер 24(3), С. 331 - 342

Опубликована: Фев. 22, 2021

Язык: Английский

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Genetic Control of Expression and Splicing in Developing Human Brain Informs Disease Mechanisms

Cell, Год журнала: 2019, Номер 179(3), С. 750 - 771.e22

Опубликована: Окт. 1, 2019

Язык: Английский

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