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

Collins, Stephan C., Mikhaleva, Anna, Vrcelj, Katarina, Vancollie, Valerie E., Wagner, Christel, Demeure, Nestor, Whitley, Helen, Kannan, Meghna, Balz, Rebecca, Anthony, Lauren F. E., Edwards, Andrew, Moine, Hervé, White, Jacqueline K., Adams, David J., Reymond, Alexandre, Lelliott, Christopher J., Webber, Caleb and Yalcin, Binnaz 2019. Large-scale neuroanatomical study uncovers 198 gene associations in mouse brain morphogenesis. Nature Communications 10 (1) , -. 10.1038/s41467-019-11431-2

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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.

Item Type: Article
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Nature Research
ISSN: 2041-1723
Date of First Compliant Deposit: 16 August 2019
Date of Acceptance: 13 July 2019
Last Modified: 19 Aug 2019 10:15
URI: http://orca-mwe.cf.ac.uk/id/eprint/124970

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