ArticleDevelopment genes and evolution2013
Exploring the effects of gene dosage on mandible shape in mice as a model for studying the genetic basis of natural variation.
Article in Development genes and evolution, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 36 citations in OpenAlex.
- Leveraging descriptor learning and functional map-based shape matching for automated anatomical Landmarking in mouse mandibles.Journal of anatomy · 2025Article
- Leveraging Descriptor Learning and Functional Map-based Shape Matching for Automatic Landmark Acquisition.bioRxiv : the preprint server for biology · 2024Article
- Predominantly inverse modulation of gene expression in genomically unbalanced disomic haploid maize.The Plant cell · 2021Article
- An empirical bayesian approach for testing gene expression fold change and its application in detecting global dosage effects.NAR genomics and bioinformatics · 2020Article
- Global impacts of chromosomal imbalance on gene expression inProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Linkage mapping of yeast cross protection connects gene expression variation to a higher-order organismal trait.PLoS genetics · 2018Article
- Cooperative interaction of BMP signalling and Foxn1 gene dosage determines the size of the functionally active thymic epithelial compartment.Scientific reports · 2017Article
- Does 3D Phenotyping Yield Substantial Insights in the Genetics of the Mouse Mandible Shape?G3 (Bethesda, Md.) · 2016Article
- Toward an orofacial gene regulatory network.Developmental dynamics : an official publication of the American Association of Anatomists · 2016Review
- Common mechanisms in development and disease: BMP signaling in craniofacial development.Cytokine & growth factor reviews · 2016Review
- Mapping of Craniofacial Traits in Outbred Mice Identifies Major Developmental Genes Involved in Shape Determination.PLoS genetics · 2015Article
- Quantitative trait loci affecting the 3D skull shape and size in mouse and prioritization of candidate genes in-silico.Frontiers in physiology · 2015Article
- Facts and artifacts in studies of gene expression in aneuploids and sex chromosomes.Chromosoma · 2014Review
- Article
- Directed Bmp4 expression in neural crest cells generates a genetic model for the rare human bony syngnathia birth defect.Developmental biology · 2014Article
- Haploinsufficiency of interferon regulatory factor 6 alters brain morphology in the mouse.American journal of medical genetics. Part A · 2014Article
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12 authors at 8 institutions in 5 countries.
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Abstract
Mandible shape in the mouse is a complex trait that is influenced by many genetic factors. However, little is known about the action of single genes on adult mandible shape so far, since most developmentally relevant genes are already required during embryogenesis, i.e., knockouts lead to embryonic death or severe deformations, before the mandible is fully formed. We employ here a geometric morphometric approach to identify subtle phenotypic differences caused by dosage effects of candidate genes. We use mouse strains with specific gene modifications (knockouts and knockins) to compare heterozygous animals with controls from the same stock, which is expected to be equivalent to a change of gene expression of the respective locus. Such differences in expression level are also likely to occur as part of the natural variation. We focus on Bmp pathway genes (Bmp4, its antagonist Noggin, and combinations of Bmp5-7 genotypes), but include also two other developmental control genes suspected to affect mandible development in some way (Egfr and Irf6). In addition, we study the effects of Hoxd13, as well as an extracellular matrix constituent (Col2a1). We find that subtle but significant shape differences are caused by differences in gene dosage of several of these genes. The changes seen for Bmp4 and Noggin are partially compatible with the action of these genes known from birds and fish. We find significant shape changes also for Hoxd13, although this gene has so far only been implicated in skeletal patterning processes of the limbs. Comparing the effect sizes of gene dosage changes to the variation found in natural populations of mice as well as quantitative trait loci (QTL) effects on mandible shape, we find that the effect sizes caused by gene dosage changes are at the lower end of the spectrum of natural variation, but larger than the average additive effects found in QTL studies. We conclude that studying gene dosage effects have the potential to provide new insights into aspects of craniofacial development, variation, and evolution.
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