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

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.

SUBMITTER: Collins SC

PROVIDER: S-EPMC6671969 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Collins Stephan C SC Mikhaleva Anna A Vrcelj Katarina K Vancollie Valerie E VE Wagner Christel C Demeure Nestor N Whitley Helen H Kannan Meghna M Balz Rebecca R Anthony Lauren F E LFE Edwards Andrew A Moine Hervé H White Jacqueline K JK Adams David J DJ Reymond Alexandre A Lelliott Christopher J CJ Webber Caleb C Yalcin Binnaz B

Nature communications 20190801 1

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, ...[more]

PMID: 31371714

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

Publications

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

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