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Oligogenic Effects of 16p11.2 Copy-Number Variation on Craniofacial Development
- Source :
- 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
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
Abstract
- 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.<br />Graphical Abstract<br />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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Database :
- OpenAIRE
- Journal :
- 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
- Accession number :
- edsair.doi.dedup.....a86d9aa1660e8e41cded8ad00a1e3f8f