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Large-scale neuroanatomical study uncovers 198 gene associations in mouse brain morphogenesis

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  • Stephan C. Collins

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964
    Université de Strasbourg)

  • Anna Mikhaleva

    (University of Lausanne)

  • Katarina Vrcelj

    (University of Oxford)

  • Valerie E. Vancollie

    (Wellcome Sanger Institute)

  • Christel Wagner

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964
    Université de Strasbourg)

  • Nestor Demeure

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964
    Université de Strasbourg)

  • Helen Whitley

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964
    Université de Strasbourg)

  • Meghna Kannan

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964
    Université de Strasbourg)

  • Rebecca Balz

    (University of Lausanne)

  • Lauren F. E. Anthony

    (Wellcome Sanger Institute)

  • Andrew Edwards

    (Woodland View Hospital, NHS Ayrshire and Arran
    Wellcome Centre for Human Genetics)

  • Hervé Moine

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964
    Université de Strasbourg)

  • Jacqueline K. White

    (Wellcome Sanger Institute)

  • David J. Adams

    (Wellcome Sanger Institute)

  • Alexandre Reymond

    (University of Lausanne)

  • Christopher J. Lelliott

    (Wellcome Sanger Institute)

  • Caleb Webber

    (University of Oxford
    University of Cardiff)

  • Binnaz Yalcin

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964
    Université de Strasbourg)

Abstract

Brain morphogenesis is an important process contributing to higher-order cognition, however our knowledge about its biological basis is largely incomplete. Here we analyze 118 neuroanatomical parameters in 1,566 mutant mouse lines and identify 198 genes whose disruptions yield NeuroAnatomical Phenotypes (NAPs), mostly affecting structures implicated in brain connectivity. Groups of functionally similar NAP genes participate in pathways involving the cytoskeleton, the cell cycle and the synapse, display distinct fetal and postnatal brain expression dynamics and importantly, their disruption can yield convergent phenotypic patterns. 17% of human unique orthologues of mouse NAP genes are known loci for cognitive dysfunction. The remaining 83% constitute a vast pool of genes newly implicated in brain architecture, providing the largest study of mouse NAP genes and pathways. This offers a complementary resource to human genetic studies and predict that many more genes could be involved in mammalian brain morphogenesis.

Suggested Citation

  • Stephan C. Collins & Anna Mikhaleva & Katarina Vrcelj & Valerie E. Vancollie & Christel Wagner & Nestor Demeure & Helen Whitley & Meghna Kannan & Rebecca Balz & Lauren F. E. Anthony & Andrew Edwards &, 2019. "Large-scale neuroanatomical study uncovers 198 gene associations in mouse brain morphogenesis," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11431-2
    DOI: 10.1038/s41467-019-11431-2
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    Cited by:

    1. Delfina M. Romero & Karine Poirier & Richard Belvindrah & Imane Moutkine & Anne Houllier & Anne-Gaëlle LeMoing & Florence Petit & Anne Boland & Stephan C. Collins & Mariano Soiza-Reilly & Binnaz Yalci, 2022. "Novel role of the synaptic scaffold protein Dlgap4 in ventricular surface integrity and neuronal migration during cortical development," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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