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  • 1
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    Spatio-temporal transcriptome of the human brain (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-10-28
    Description: 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566780/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566780/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kang, Hyo Jung -- Kawasawa, Yuka Imamura -- Cheng, Feng -- Zhu, Ying -- Xu, Xuming -- Li, Mingfeng -- Sousa, Andre M M -- Pletikos, Mihovil -- Meyer, Kyle A -- Sedmak, Goran -- Guennel, Tobias -- Shin, Yurae -- Johnson, Matthew B -- Krsnik, Zeljka -- Mayer, Simone -- Fertuzinhos, Sofia -- Umlauf, Sheila -- Lisgo, Steven N -- Vortmeyer, Alexander -- Weinberger, Daniel R -- Mane, Shrikant -- Hyde, Thomas M -- Huttner, Anita -- Reimers, Mark -- Kleinman, Joel E -- Sestan, Nenad -- DA026119/DA/NIDA NIH HHS/ -- G0700089/Medical Research Council/United Kingdom -- G9900837/Medical Research Council/United Kingdom -- GR082557/Wellcome Trust/United Kingdom -- HD000836/HD/NICHD NIH HHS/ -- MH081896/MH/NIMH NIH HHS/ -- MH089929/MH/NIMH NIH HHS/ -- NS054273/NS/NINDS NIH HHS/ -- R01 NS054273/NS/NINDS NIH HHS/ -- R01 NS054273-07/NS/NINDS NIH HHS/ -- RC2 MH089929/MH/NIMH NIH HHS/ -- RC2 MH089929-02/MH/NIMH NIH HHS/ -- U01 MH081896/MH/NIMH NIH HHS/ -- U01 MH081896-03/MH/NIMH NIH HHS/ -- England -- Nature. 2011 Oct 26;478(7370):483-9. doi: 10.1038/nature10523.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22031440" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/*genetics ; Brain/embryology/*growth & development/*metabolism ; Child ; Child, Preschool ; Exons/genetics ; Female ; Fetus/metabolism ; *Gene Expression Profiling ; Gene Expression Regulation, Developmental/*genetics ; Gene Regulatory Networks/genetics ; Humans ; Infant ; Male ; Middle Aged ; Quality Control ; Quantitative Trait Loci/genetics ; Sex Characteristics ; Time Factors ; Transcriptome/*genetics ; Young Adult
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Human metabolic individuality in biomedical and pharmaceutical research (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-09-03
    Description: Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832838/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832838/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suhre, Karsten -- Shin, So-Youn -- Petersen, Ann-Kristin -- Mohney, Robert P -- Meredith, David -- Wagele, Brigitte -- Altmaier, Elisabeth -- CARDIoGRAM -- Deloukas, Panos -- Erdmann, Jeanette -- Grundberg, Elin -- Hammond, Christopher J -- de Angelis, Martin Hrabe -- Kastenmuller, Gabi -- Kottgen, Anna -- Kronenberg, Florian -- Mangino, Massimo -- Meisinger, Christa -- Meitinger, Thomas -- Mewes, Hans-Werner -- Milburn, Michael V -- Prehn, Cornelia -- Raffler, Johannes -- Ried, Janina S -- Romisch-Margl, Werner -- Samani, Nilesh J -- Small, Kerrin S -- Wichmann, H-Erich -- Zhai, Guangju -- Illig, Thomas -- Spector, Tim D -- Adamski, Jerzy -- Soranzo, Nicole -- Gieger, Christian -- 091746/Wellcome Trust/United Kingdom -- 091746/Z/10/Z/Wellcome Trust/United Kingdom -- 1R01HL103931-01/HL/NHLBI NIH HHS/ -- HL087647/HL/NHLBI NIH HHS/ -- MOP172605/Canadian Institutes of Health Research/Canada -- MOP77682/Canadian Institutes of Health Research/Canada -- MOP-82810/Canadian Institutes of Health Research/Canada -- N01-AG-12100/AG/NIA NIH HHS/ -- N01-HC-55015/HC/NHLBI NIH HHS/ -- N01-HC-55016/HC/NHLBI NIH HHS/ -- N01-HC-55018/HC/NHLBI NIH HHS/ -- N01-HC-55019/HC/NHLBI NIH HHS/ -- N01-HC-55020/HC/NHLBI NIH HHS/ -- N01-HC-55021/HC/NHLBI NIH HHS/ -- N01-HC-55022/HC/NHLBI NIH HHS/ -- P01 HL098055/HL/NHLBI NIH HHS/ -- P01HL076491-06/HL/NHLBI NIH HHS/ -- P01HL087018/HL/NHLBI NIH HHS/ -- R01 HL087647/HL/NHLBI NIH HHS/ -- R01 HL087676/HL/NHLBI NIH HHS/ -- R01DK080732/DK/NIDDK NIH HHS/ -- R01HL089650-02/HL/NHLBI NIH HHS/ -- Biotechnology and Biological Sciences Research Council/United Kingdom -- British Heart Foundation/United Kingdom -- Cancer Research UK/United Kingdom -- Intramural NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2011 Aug 31;477(7362):54-60. doi: 10.1038/nature10354.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Ingolstadter Landstrasse 1, 85764 Neuherberg, Germany. karsten@suhre.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21886157" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Biomedical Research ; Blood/metabolism ; Child ; Chronic Disease ; Coronary Artery Disease/genetics ; Diabetes Mellitus/genetics ; *Drug Industry ; Female ; Genetic Loci/genetics ; *Genetic Variation ; *Genome-Wide Association Study ; Genotype ; Humans ; Male ; Metabolism/*genetics ; Metabolomics ; Middle Aged ; Pharmacogenetics ; Renal Insufficiency/genetics ; Risk Factors ; Venous Thromboembolism/genetics ; Young Adult
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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