Oligogenic Effects of 16p11.2 Copy-Number Variation on Craniofacial Development
| Autor: | Erica E. Davis, Omar Shanta, Curtis K. Deutsch, Yann Herault, Jonathan Sebat, Shawn Cho, Claire Chevalier, Christina Corsello, Nicholas Katsanis, Sandra Martin Lorenzo, Pang Timothy, Ellen Richardson, Yuqi Qiu, Hongying Li, Oanh Hong, Lilia M. Iakoucheva, Karen Messer, Shih C. Tang, Thomas Arbogast |
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| Přispěvatelé: | Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Autism and Communicative Disorders Centre, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, School of Oceanography [Seattle], University of Washington [Seattle], Center for Human Disease Modeling, Duke University [Durham] |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Head size Male [SDV]Life Sciences [q-bio] ved/biology.organism_classification_rank.species Medical Physiology Chromosome Disorders Craniofacial Abnormalities 0302 clinical medicine Gene duplication 2.1 Biological and endogenous factors Copy-number variation Aetiology Zebrafish lcsh:QH301-705.5 ComputingMilieux_MISCELLANEOUS Genetics Pediatric biology Phenotype Mental Health Female Chromosome Deletion Human Biotechnology DNA Copy Number Variations General Biochemistry Genetics and Molecular Biology Chromosomes Article 03 medical and health sciences Clinical Research Intellectual Disability Humans Craniofacial Dental/Oral and Craniofacial Disease Autistic Disorder Model organism Gene [SDV.GEN]Life Sciences [q-bio]/Genetics ved/biology Pair 16 Human Genome biology.organism_classification Brain Disorders 030104 developmental biology lcsh:Biology (General) Congenital Structural Anomalies Biochemistry and Cell Biology 030217 neurology & neurosurgery Chromosomes Human Pair 16 |
| Zdroj: | Cell Reports Cell Reports, Elsevier Inc, 2019, 28 (13), pp.3320-3328.e4. ⟨10.1016/j.celrep.2019.08.071⟩ Cell Reports, Vol 28, Iss 13, Pp 3320-3328.e4 (2019) Cell reports Cell reports, vol 28, iss 13 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2019.08.071⟩ |
| Popis: | SUMMARY A copy-number variant (CNV) of 16p11.2 encompassing 30 genes is associated with developmental and psychiatric disorders, head size, and body mass. The genetic mechanisms that underlie these associations are not understood. To determine the influence of 16p11.2 genes on development, we investigated the effects of CNV on craniofacial structure in humans and model organisms. We show that deletion and duplication of 16p11.2 have “mirror” effects on specific craniofacial features that are conserved between human and rodent models of the CNV. By testing dosage effects of individual genes on the shape of the mandible in zebrafish, we identify seven genes with significant effects individually and find evidence for others when genes were tested in combination. The craniofacial phenotypes of 16p11.2 CNVs represent a model for studying the effects of genes on development, and our results suggest that the associated facial gestalts are attributable to the combined effects of multiple genes. Graphical Abstract In Brief Using 3D morphometric imaging, Qiu et al. demonstrate that large copy-number variants (CNVs) of 16p11.2 have significant effects on craniofacial structure that are conserved in humans and model organisms, and they demonstrate that these craniofacial phenotypes are attributable to the dosage effects of multiple genes within the CNV region. |
| Databáze: | OpenAIRE |
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