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Nat Commun. 2019 Aug 1;10(1):3465. doi: 10.1038/s41467-019-11431-2.

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

Collins SC1,2,3,4,5, Mikhaleva A6, Vrcelj K7, Vancollie VE8, Wagner C1,2,3,4, Demeure N1,2,3,4, Whitley H1,2,3,4, Kannan M1,2,3,4, Balz R6, Anthony LFE8, Edwards A9,10, Moine H1,2,3,4, White JK8, Adams DJ8, Reymond A6, Lelliott CJ8, Webber C7,11, Yalcin B12,13,14,15,16.

Author information

1
Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404, Illkirch, France.
2
Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France.
3
Institut National de la Santé et de la Recherche Médicale, U964, 67404, Illkirch, France.
4
Université de Strasbourg, 67404, Illkirch, France.
5
Inserm UMR1231 GAD, University of Bourgogne Franche-Comté, 21000, Dijon, France.
6
Center for Integrative Genomics, University of Lausanne, 1015, Lausanne, Switzerland.
7
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.
8
Wellcome Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
9
Woodland View Hospital, NHS Ayrshire and Arran, Irvine, KA12 8SS, Scotland.
10
Wellcome Centre for Human Genetics, Oxford, OX3 7BN, UK.
11
UK Dementia Research Institute, University of Cardiff, Cardiff, CF24 2HQ, UK.
12
Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404, Illkirch, France. Binnaz.Yalcin@igbmc.fr.
13
Centre National de la Recherche Scientifique, UMR7104, 67404, Illkirch, France. Binnaz.Yalcin@igbmc.fr.
14
Institut National de la Santé et de la Recherche Médicale, U964, 67404, Illkirch, France. Binnaz.Yalcin@igbmc.fr.
15
Université de Strasbourg, 67404, Illkirch, France. Binnaz.Yalcin@igbmc.fr.
16
Center for Integrative Genomics, University of Lausanne, 1015, Lausanne, Switzerland. Binnaz.Yalcin@igbmc.fr.

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.

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