Temporal dynamics and genetic control of transcription in the human prefrontal cortex
Gene expression in the human brain Gene expression controls and dictates everything from development and plasticity to ongoing neurogenesis in the brain, yet the temporal dynamics of transcription throughout the brain's lifetime have been mostly unknown. Here, two groups present a large gene-ex...
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| Published in | Nature (London) Vol. 478; no. 7370; pp. 519 - 523 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
27.10.2011
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Gene expression in the human brain
Gene expression controls and dictates everything from development and plasticity to ongoing neurogenesis in the brain, yet the temporal dynamics of transcription throughout the brain's lifetime have been mostly unknown. Here, two groups present a large gene-expression database from a variety of human brain samples ranging from before birth to over 80 years in age. Colantuoni
et al
. focus on the prefrontal cortex. Although they note significant expression pattern dynamics throughout development, they identify a consistent molecular architecture of transcription across subjects from different races despite the large number of genetic polymorphisms among them. Kang
et al
. produce a more comprehensive time course, exploring expression in 16 different brain areas, determining that the largest spatiotemporal variability occurs before birth, with transcriptomes in brain regions converging as we age.
Previous investigations have combined transcriptional and genetic analyses in human cell lines
1
,
2
,
3
, but few have applied these techniques to human neural tissue
4
,
5
,
6
,
7
,
8
. To gain a global molecular perspective on the role of the human genome in cortical development, function and ageing, we explore the temporal dynamics and genetic control of transcription in human prefrontal cortex in an extensive series of post-mortem brains from fetal development through ageing. We discover a wave of gene expression changes occurring during fetal development which are reversed in early postnatal life. One half-century later in life, this pattern of reversals is mirrored in ageing and in neurodegeneration. Although we identify thousands of robust associations of individual genetic polymorphisms with gene expression, we also demonstrate that there is no association between the total extent of genetic differences between subjects and the global similarity of their transcriptional profiles. Hence, the human genome produces a consistent molecular architecture in the prefrontal cortex, despite millions of genetic differences across individuals and races. To enable further discovery, this entire data set is freely available (from Gene Expression Omnibus: accession GSE30272; and dbGaP: accession phs000417.v1.p1) and can also be interrogated via a biologist-friendly stand-alone application (
http://www.libd.org/braincloud
). |
|---|---|
| AbstractList | Previous investigations have combined transcriptional and genetic analyses in human cell lines, but few have applied these techniques to human neural tissue. To gain a global molecular perspective on the role of the human genome in cortical development, function and ageing, we explore the temporal dynamics and genetic control of transcription in human prefrontal cortex in an extensive series of post-mortem brains from fetal development through ageing. We discover a wave of gene expression changes occurring during fetal development which are reversed in early postnatal life. One half-century later in life, this pattern of reversals is mirrored in ageing and in neurodegeneration. Although we identify thousands of robust associations of individual genetic polymorphisms with gene expression, we also demonstrate that there is no association between the total extent of genetic differences between subjects and the global similarity of their transcriptional profiles. Hence, the human genome produces a consistent molecular architecture in the prefrontal cortex, despite millions of genetic differences across individuals and races. To enable further discovery, this entire data set is freely available (from Gene Expression Omnibus: accession GSE30272; and dbGaP: accession phs000417.v1.p1) and can also be interrogated via a biologist-friendly stand-alone application (http://www.libd.org/braincloud). Previous investigations have combined transcriptional and genetic analyses in human cell lines, but few have applied these techniques to human neural tissue. To gain a global molecular perspective on the role of the human genome in cortical development, function and ageing, we explore the temporal dynamics and genetic control of transcription in human prefrontal cortex in an extensive series of post-mortem brains from fetal development through ageing. We discover a wave of gene expression changes occurring during fetal development which are reversed in early postnatal life. One half-century later in life, this pattern of reversals is mirrored in ageing and in neurodegeneration. Although we identify thousands of robust associations of individual genetic polymorphisms with gene expression, we also demonstrate that there is no association between the total extent of genetic differences between subjects and the global similarity of their transcriptional profiles. Hence, the human genome produces a consistent molecular architecture in the prefrontal cortex, despite millions of genetic differences across individuals and races. To enable further discovery, this entire data set is freely available (from Gene Expression Omnibus: accession GSE30272; and dbGaP: accession phs000417.v1.p1) and can also be interrogated via a biologist-friendly stand-alone application (http://www.libd.org/braincloud).Previous investigations have combined transcriptional and genetic analyses in human cell lines, but few have applied these techniques to human neural tissue. To gain a global molecular perspective on the role of the human genome in cortical development, function and ageing, we explore the temporal dynamics and genetic control of transcription in human prefrontal cortex in an extensive series of post-mortem brains from fetal development through ageing. We discover a wave of gene expression changes occurring during fetal development which are reversed in early postnatal life. One half-century later in life, this pattern of reversals is mirrored in ageing and in neurodegeneration. Although we identify thousands of robust associations of individual genetic polymorphisms with gene expression, we also demonstrate that there is no association between the total extent of genetic differences between subjects and the global similarity of their transcriptional profiles. Hence, the human genome produces a consistent molecular architecture in the prefrontal cortex, despite millions of genetic differences across individuals and races. To enable further discovery, this entire data set is freely available (from Gene Expression Omnibus: accession GSE30272; and dbGaP: accession phs000417.v1.p1) and can also be interrogated via a biologist-friendly stand-alone application (http://www.libd.org/braincloud). Gene expression in the human brain Gene expression controls and dictates everything from development and plasticity to ongoing neurogenesis in the brain, yet the temporal dynamics of transcription throughout the brain's lifetime have been mostly unknown. Here, two groups present a large gene-expression database from a variety of human brain samples ranging from before birth to over 80 years in age. Colantuoni et al . focus on the prefrontal cortex. Although they note significant expression pattern dynamics throughout development, they identify a consistent molecular architecture of transcription across subjects from different races despite the large number of genetic polymorphisms among them. Kang et al . produce a more comprehensive time course, exploring expression in 16 different brain areas, determining that the largest spatiotemporal variability occurs before birth, with transcriptomes in brain regions converging as we age. Previous investigations have combined transcriptional and genetic analyses in human cell lines 1 , 2 , 3 , but few have applied these techniques to human neural tissue 4 , 5 , 6 , 7 , 8 . To gain a global molecular perspective on the role of the human genome in cortical development, function and ageing, we explore the temporal dynamics and genetic control of transcription in human prefrontal cortex in an extensive series of post-mortem brains from fetal development through ageing. We discover a wave of gene expression changes occurring during fetal development which are reversed in early postnatal life. One half-century later in life, this pattern of reversals is mirrored in ageing and in neurodegeneration. Although we identify thousands of robust associations of individual genetic polymorphisms with gene expression, we also demonstrate that there is no association between the total extent of genetic differences between subjects and the global similarity of their transcriptional profiles. Hence, the human genome produces a consistent molecular architecture in the prefrontal cortex, despite millions of genetic differences across individuals and races. To enable further discovery, this entire data set is freely available (from Gene Expression Omnibus: accession GSE30272; and dbGaP: accession phs000417.v1.p1) and can also be interrogated via a biologist-friendly stand-alone application ( http://www.libd.org/braincloud ). Previous investigations have combined transcriptional and genetic analyses in human cell lines 1 - 3 , but few have applied these techniques to human neural tissue 4 - 8 . To gain a global molecular perspective on the role of the human genome in cortical development, function and ageing, we explore the temporal dynamics and genetic control of transcription in human prefrontal cortex in an extensive series of post-mortem brains from fetal development through ageing. We discover a wave of gene expression changes occurring during fetal development which are reversed in early postnatal life. One half-century later in life, this pattern of reversals is mirrored in ageing and in neurodegeneration. Although we identify thousands of robust associations of individual genetic polymorphisms with gene expression, we also demonstrate that there is no association between the total extent of genetic differences between subjects and the global similarity of their transcriptional profiles. Hence, the human genome produces a consistent molecular architecture in the prefrontal cortex, despite millions of genetic differences across individuals and races. To enable further discovery, this entire data set is freely available (from Gene Expression Omnibus: accession GSE30272; and dbGaP: accession phs000417.v1.p1) and can also be interrogated via a biologist-friendly stand-alone application ( http://www.libd.org/braincloud ). Previous investigations have combined transcriptional and genetic analyses in human cell lines, but few have applied these techniques to human neural tissue. To gain a global molecular perspective on the role of the human genome in cortical development, function and ageing, we explore the temporal dynamics and genetic control of transcription in human prefrontal cortex in an extensive series of post-mortem brains from fetal development through ageing. We discover a wave of gene expression changes occurring during fetal development which are reversed in early postnatal life. One half-century later in life, this pattern of reversals is mirrored in ageing and in neurodegeneration. Although we identify thousands of robust associations of individual genetic polymorphisms with gene expression, we also demonstrate that there is no association between the total extent of genetic differences between subjects and the global similarity of their transcriptional profiles. Hence, the human genome produces a consistent molecular architecture in the prefrontal cortex, despite millions of genetic differences across individuals and races. To enable further discovery, this entire data set is freely available (from Gene Expression Omnibus: accession GSE30272; and dbGaP: accession phs000417.v1.p1) and can also be interrogated via a biologist-friendly stand-alone application (http://www.libd.org/braincloud). [PUBLICATION ABSTRACT] |
| Author | Colantuoni, Carlo Ye, Tianzhang Kleinman, Joel E. Herman, Mary M. Hyde, Thomas M. Tao, Ran Leek, Jeffrey T. Colantuoni, Elizabeth A. Weinberger, Daniel R. Lipska, Barbara K. Elkahloun, Abdel G. |
| AuthorAffiliation | 3 Illuminato Biotechnology, Inc., Baltimore, Maryland 21211, USA 1 Section on Neuropathology, Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, IRP, NIMH, NIH, Bethesda, Maryland 20892, USA 4 The Lieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, Maryland 21205, USA 5 Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA 2 Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA |
| AuthorAffiliation_xml | – name: 4 The Lieber Institute for Brain Development, Johns Hopkins University Medical Center, Baltimore, Maryland 21205, USA – name: 3 Illuminato Biotechnology, Inc., Baltimore, Maryland 21211, USA – name: 2 Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA – name: 1 Section on Neuropathology, Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, IRP, NIMH, NIH, Bethesda, Maryland 20892, USA – name: 5 Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA |
| Author_xml | – sequence: 1 givenname: Carlo surname: Colantuoni fullname: Colantuoni, Carlo organization: Section on Neuropathology, Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, IRP, NIMH, NIH, Bethesda, Maryland 20892, USA, Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Illuminato Biotechnology, Inc., The Lieber Institute for Brain Development, Johns Hopkins University Medical Center – sequence: 2 givenname: Barbara K. surname: Lipska fullname: Lipska, Barbara K. organization: Section on Neuropathology, Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, IRP, NIMH, NIH, Bethesda, Maryland 20892, USA – sequence: 3 givenname: Tianzhang surname: Ye fullname: Ye, Tianzhang organization: Section on Neuropathology, Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, IRP, NIMH, NIH, Bethesda, Maryland 20892, USA – sequence: 4 givenname: Thomas M. surname: Hyde fullname: Hyde, Thomas M. organization: Section on Neuropathology, Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, IRP, NIMH, NIH, Bethesda, Maryland 20892, USA, The Lieber Institute for Brain Development, Johns Hopkins University Medical Center – sequence: 5 givenname: Ran surname: Tao fullname: Tao, Ran organization: Section on Neuropathology, Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, IRP, NIMH, NIH, Bethesda, Maryland 20892, USA – sequence: 6 givenname: Jeffrey T. surname: Leek fullname: Leek, Jeffrey T. organization: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health – sequence: 7 givenname: Elizabeth A. surname: Colantuoni fullname: Colantuoni, Elizabeth A. organization: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health – sequence: 8 givenname: Abdel G. surname: Elkahloun fullname: Elkahloun, Abdel G. organization: Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health – sequence: 9 givenname: Mary M. surname: Herman fullname: Herman, Mary M. organization: Section on Neuropathology, Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, IRP, NIMH, NIH, Bethesda, Maryland 20892, USA – sequence: 10 givenname: Daniel R. surname: Weinberger fullname: Weinberger, Daniel R. organization: Section on Neuropathology, Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, IRP, NIMH, NIH, Bethesda, Maryland 20892, USA, The Lieber Institute for Brain Development, Johns Hopkins University Medical Center – sequence: 11 givenname: Joel E. surname: Kleinman fullname: Kleinman, Joel E. email: kleinmaj@mail.nih.gov organization: Section on Neuropathology, Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, IRP, NIMH, NIH, Bethesda, Maryland 20892, USA |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24636343$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/22031444$$D View this record in MEDLINE/PubMed |
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| Keywords | Human Cerebral cortex Transcription Genetic determinism Central nervous system Encephalon |
| Language | English |
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| Snippet | Gene expression in the human brain
Gene expression controls and dictates everything from development and plasticity to ongoing neurogenesis in the brain, yet... Previous investigations have combined transcriptional and genetic analyses in human cell lines, but few have applied these techniques to human neural tissue.... Previous investigations have combined transcriptional and genetic analyses in human cell lines 1 - 3 , but few have applied these techniques to human neural... |
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| SubjectTerms | 631/208/191/2018 631/208/200 631/208/212 631/378/1457/1945 Aging Aging - genetics Autopsy Biological and medical sciences Fetus - metabolism Fundamental and applied biological sciences. Psychology Gene expression Gene Expression Profiling Gene Expression Regulation, Developmental - genetics Genome, Human - genetics Genomes Humanities and Social Sciences Humans letter Molecular and cellular biology Molecular genetics multidisciplinary Polymorphism, Single Nucleotide - genetics Prefrontal Cortex - embryology Prefrontal Cortex - growth & development Prefrontal Cortex - metabolism Principal components analysis Racial Groups - genetics Science Science (multidisciplinary) Time Factors Transcription. Transcription factor. Splicing. Rna processing Transcriptome - genetics |
| Title | Temporal dynamics and genetic control of transcription in the human prefrontal cortex |
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