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

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 investiga...

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Autores principales: Driessens, Stan L. W., Galakhova, Anna A., Heyer, Djai B., Pieterse, Isabel J., Wilbers, René, Mertens, Eline J., Waleboer, Femke, Heistek, Tim S., Coenen, Loet, Meijer, Julia R., Idema, Sander, de Witt Hamer, Philip C., Noske, David P., de Kock, Christiaan P. J., Lee, Brian R., Smith, Kimberly, Ting, Jonathan T., Lein, Ed S., Mansvelder, Huibert D., Goriounova, Natalia A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10345092/
https://www.ncbi.nlm.nih.gov/pubmed/37443107
http://dx.doi.org/10.1038/s41467-023-39946-9
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author Driessens, Stan L. W.
Galakhova, Anna A.
Heyer, Djai B.
Pieterse, Isabel J.
Wilbers, René
Mertens, Eline J.
Waleboer, Femke
Heistek, Tim S.
Coenen, Loet
Meijer, Julia R.
Idema, Sander
de Witt Hamer, Philip C.
Noske, David P.
de Kock, Christiaan P. J.
Lee, Brian R.
Smith, Kimberly
Ting, Jonathan T.
Lein, Ed S.
Mansvelder, Huibert D.
Goriounova, Natalia A.
author_facet Driessens, Stan L. W.
Galakhova, Anna A.
Heyer, Djai B.
Pieterse, Isabel J.
Wilbers, René
Mertens, Eline J.
Waleboer, Femke
Heistek, Tim S.
Coenen, Loet
Meijer, Julia R.
Idema, Sander
de Witt Hamer, Philip C.
Noske, David P.
de Kock, Christiaan P. J.
Lee, Brian R.
Smith, Kimberly
Ting, Jonathan T.
Lein, Ed S.
Mansvelder, Huibert D.
Goriounova, Natalia A.
author_sort Driessens, Stan L. W.
collection PubMed
description 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.
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spelling pubmed-103450922023-07-15 Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types Driessens, Stan L. W. Galakhova, Anna A. Heyer, Djai B. Pieterse, Isabel J. Wilbers, René Mertens, Eline J. Waleboer, Femke Heistek, Tim S. Coenen, Loet Meijer, Julia R. Idema, Sander de Witt Hamer, Philip C. Noske, David P. de Kock, Christiaan P. J. Lee, Brian R. Smith, Kimberly Ting, Jonathan T. Lein, Ed S. Mansvelder, Huibert D. Goriounova, Natalia A. Nat Commun Article 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. Nature Publishing Group UK 2023-07-13 /pmc/articles/PMC10345092/ /pubmed/37443107 http://dx.doi.org/10.1038/s41467-023-39946-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Driessens, Stan L. W.
Galakhova, Anna A.
Heyer, Djai B.
Pieterse, Isabel J.
Wilbers, René
Mertens, Eline J.
Waleboer, Femke
Heistek, Tim S.
Coenen, Loet
Meijer, Julia R.
Idema, Sander
de Witt Hamer, Philip C.
Noske, David P.
de Kock, Christiaan P. J.
Lee, Brian R.
Smith, Kimberly
Ting, Jonathan T.
Lein, Ed S.
Mansvelder, Huibert D.
Goriounova, Natalia A.
Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types
title Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types
title_full Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types
title_fullStr Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types
title_full_unstemmed Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types
title_short Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types
title_sort genes associated with cognitive ability and har show overlapping expression patterns in human cortical neuron types
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10345092/
https://www.ncbi.nlm.nih.gov/pubmed/37443107
http://dx.doi.org/10.1038/s41467-023-39946-9
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