PUBLICATION
Oligogenic Effects of 16p11.2 Copy-Number Variation on Craniofacial Development
- Authors
- Qiu, Y., Arbogast, T., Lorenzo, S.M., Li, H., Tang, S.C., Richardson, E., Hong, O., Cho, S., Shanta, O., Pang, T., Corsello, C., Deutsch, C.K., Chevalier, C., Davis, E.E., Iakoucheva, L.M., Herault, Y., Katsanis, N., Messer, K., Sebat, J.
- ID
- ZDB-PUB-190926-10
- Date
- 2019
- Source
- Cell Reports 28: 3320-3328.e4 (Journal)
- Registered Authors
- Davis, Erica, Katsanis, Nicholas
- Keywords
- none
- MeSH Terms
-
- Autistic Disorder/genetics*
- Chromosome Deletion
- Chromosome Disorders/genetics*
- Chromosomes, Human, Pair 16/genetics
- Craniofacial Abnormalities/genetics*
- DNA Copy Number Variations/genetics*
- Female
- Humans
- Intellectual Disability/genetics*
- Male
- PubMed
- 31553903 Full text @ Cell Rep.
Citation
Qiu, Y., Arbogast, T., Lorenzo, S.M., Li, H., Tang, S.C., Richardson, E., Hong, O., Cho, S., Shanta, O., Pang, T., Corsello, C., Deutsch, C.K., Chevalier, C., Davis, E.E., Iakoucheva, L.M., Herault, Y., Katsanis, N., Messer, K., Sebat, J. (2019) Oligogenic Effects of 16p11.2 Copy-Number Variation on Craniofacial Development. Cell Reports. 28:3320-3328.e4.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping