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Modularity in the mammalian dentition: mice and monkeys share a common dental genetic architecture.

ABSTRACT: The concept of modularity provides a useful tool for exploring the relationship between genotype and phenotype. Here, we use quantitative genetics to identify modularity within the mammalian dentition, connecting the genetics of organogenesis to the genetics of population-level variation for a phenotype well represented in the fossil record. We estimated the correlations between dental traits owing to the shared additive effects of genes (pleiotropy) and compared the pleiotropic relationships among homologous traits in two evolutionary distant taxa-mice and baboons. We find that in both mice and baboons, who shared a common ancestor >65 Ma, incisor size variation is genetically independent of molar size variation. Furthermore, baboon premolars show independent genetic variation from incisors, suggesting that a modular genetic architecture separates incisors from these posterior teeth as well. Such genetic independence between modules provides an explanation for the extensive diversity of incisor size variation seen throughout mammalian evolution-variation uncorrelated with equivalent levels of postcanine tooth size variation. The modularity identified here is supported by the odontogenic homeobox code proposed for the patterning of the rodent dentition. The baboon postcanine pattern of incomplete pleiotropy is also consistent with predictions from the morphogenetic field model.

SUBMITTER: Hlusko LJ

PROVIDER: S-EPMC3095220 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Modularity in the mammalian dentition: mice and monkeys share a common dental genetic architecture.

Hlusko Leslea J LJ Sage Richard D RD Mahaney Michael C MC

Journal of experimental zoology. Part B, Molecular and developmental evolution 20110101 1

The concept of modularity provides a useful tool for exploring the relationship between genotype and phenotype. Here, we use quantitative genetics to identify modularity within the mammalian dentition, connecting the genetics of organogenesis to the genetics of population-level variation for a phenotype well represented in the fossil record. We estimated the correlations between dental traits owing to the shared additive effects of genes (pleiotropy) and compared the pleiotropic relationships am ...[more]

PMID: 20922775

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Project description:Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP). The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden) and human cholesteryl ester transfer protein (CETP). The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear regression showed that the combined variations in plasma metabolites, including LDL/VLDL-cholesterol, trimethylamine N-oxide (TMAO), arginine, glucose and insulin, account for approximately 30 to 40% of the variation in atherosclerotic lesion area. Overall, our data provide a rich resource for studies of complex interactions underlying atherosclerosis.

Dataset Information

Modularity in the mammalian dentition: mice and monkeys share a common dental genetic architecture.

Publications

Modularity in the mammalian dentition: mice and monkeys share a common dental genetic architecture.

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