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Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types

by Smith, Kimberly , Heistek, Tim S. , de Kock, Christiaan P. J. , Galakhova, Anna A. , Mertens, Eline J. , Noske, David P. , Goriounova, Natalia A. , Coenen, Loet , Wilbers, René , Meijer, Julia R. , Pieterse, Isabel J. , Waleboer, Femke , Ting, Jonathan T. , Heyer, Djai B. , Lein, Ed S. , Mansvelder, Huibert D. , Idema, Sander , Driessens, Stan L. W. , Lee, Brian R. , de Witt Hamer, Philip C.

in 13 / 38 / 38/91 / 631/378/2583 / 631/378/2649 / 631/378/87 / 9/74 / Action potential / Adult / Biological activity / Brain / Cellular structure / Cognition / Cognitive ability / Evolution / Evolutionary genetics / Gene expression / Genes / Humanities and Social Sciences / Humans / Kinetics / multidisciplinary / Neurons / Neurons - metabolism / Pyramidal cells / Pyramidal Cells - physiology / Science / Science (multidisciplinary) / Structure-function relationships / Temporal gyrus / Temporal Lobe / Transcriptomics

2023

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Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types

2023

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2023

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Journal Article

Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types

Smith, Kimberly,

Heistek, Tim S.,

de Kock, Christiaan P. J.,

Galakhova, Anna A.,

Mertens, Eline J.,

Noske, David P.,

Goriounova, Natalia A.,

Coenen, Loet,

Wilbers, René,

Meijer, Julia R.,

Pieterse, Isabel J.,

Waleboer, Femke,

Ting, Jonathan T.,

Heyer, Djai B.,

Lein, Ed S.,

Mansvelder, Huibert D.,

Idema, Sander,

Driessens, Stan L. W.,

Lee, Brian R.,

de Witt Hamer, Philip C.

2023

Overview

GWAS have identified numerous genes associated with human cognition but their cell type expression profiles in the human brain are unknown. These genes overlap with human accelerated regions (HARs) implicated in human brain evolution and might act on the same biological processes. Here, we investigated whether these gene sets are expressed in adult human cortical neurons, and how their expression relates to neuronal function and structure. We find that these gene sets are preferentially expressed in L3 pyramidal neurons in middle temporal gyrus (MTG). Furthermore, neurons with higher expression had larger total dendritic length (TDL) and faster action potential (AP) kinetics, properties previously linked to intelligence. We identify a subset of genes associated with TDL or AP kinetics with predominantly synaptic functions and high abundance of HARs. Using transcriptomic data from human brain cells, the authors show that the expression patterns of the genes implicated in human cognition and brain evolution overlap in specific neuron types, and relate to cellular function and structure.

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Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

/ 38

/ 38/91

/ 9/74