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Spatio-temporal transcriptome of the human brain.

Nature | Oct 26, 2011

Brain development and function depend on the precise regulation of gene expression. However, our understanding of the complexity and dynamics of the transcriptome of the human brain is incomplete. Here we report the generation and analysis of exon-level transcriptome and associated genotyping data, representing males and females of different ethnicities, from multiple brain regions and neocortical areas of developing and adult post-mortem human brains. We found that 86 per cent of the genes analysed were expressed, and that 90 per cent of these were differentially regulated at the whole-transcript or exon level across brain regions and/or time. The majority of these spatio-temporal differences were detected before birth, with subsequent increases in the similarity among regional transcriptomes. The transcriptome is organized into distinct co-expression networks, and shows sex-biased gene expression and exon usage. We also profiled trajectories of genes associated with neurobiological categories and diseases, and identified associations between single nucleotide polymorphisms and gene expression. This study provides a comprehensive data set on the human brain transcriptome and insights into the transcriptional foundations of human neurodevelopment.

Pubmed ID: 22031440 RIS Download

Mesh terms: Adolescent | Adult | Aged | Aged, 80 and over | Aging | Brain | Child | Child, Preschool | Exons | Female | Fetus | Gene Expression Profiling | Gene Expression Regulation, Developmental | Gene Regulatory Networks | Humans | Infant | Male | Middle Aged | Quality Control | Quantitative Trait Loci | Sex Characteristics | Time Factors | Transcriptome | Young Adult

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Associated grants

  • Agency: NIDA NIH HHS, Id: R25 DA026119
  • Agency: NINDS NIH HHS, Id: NS054273
  • Agency: NIMH NIH HHS, Id: RC2 MH089929-02
  • Agency: NINDS NIH HHS, Id: U24 NS051869
  • Agency: NICHD NIH HHS, Id: HD000836
  • Agency: NINDS NIH HHS, Id: R01 NS054273-07
  • Agency: NIMH NIH HHS, Id: U01 MH081896-03
  • Agency: NINDS NIH HHS, Id: R01 NS054273
  • Agency: Medical Research Council, Id: G9900837
  • Agency: NIMH NIH HHS, Id: U01 MH081896
  • Agency: Wellcome Trust, Id: GR082557
  • Agency: NICHD NIH HHS, Id: R24 HD000836
  • Agency: NIMH NIH HHS, Id: MH089929
  • Agency: NIDA NIH HHS, Id: DA026119
  • Agency: Medical Research Council, Id: G0700089
  • Agency: NIMH NIH HHS, Id: RC2 MH089929
  • Agency: NIMH NIH HHS, Id: MH081896

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Human Developmental Biology Resource

Collection of human embryonic and fetal material (Tissue and RNA) ranging from 3 to 20 weeks of development available to the international scientific community. Material can either be sent to registered users or our In House Gene Expression Service (IHGES) can carry out projects on user''''s behalf, providing high quality images and interpretation of gene expression patterns. Gene expression data emerging from HDBR material is added to our gene expression database which is accessible via our HUDSEN (Human Developmental Studies Network) website. A significant proportion of the material has been cytogenetically karyotyped, and normal karyotyped material is provided for research.

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