The long-term objective of this research project is to enhance our understanding of the genetic underpinnings of the mammalian craniofacial skeleton through the use of a marsupial model. Marsupials have already become a valuable model organism for several human conditions, such as skin and eye cancer, hypercholesterolemia and spinal cord injury. This research expands their use to include craniofacial research, for two main reasons. First, little is known about the genetic underpinnings of morphological variation in species from this mammalian infraclass. Second, Dr. John VandeBerg from the Texas Biomedical Research Institute (TBRI) has for long maintained an extremely useful captive breeding population of Monodelphis domestica, containing individuals with known pedigrees and several quasi-inbred lines. Therefore, this research project will take advantage of this captive breeding population of the gray short-tailed opossum and carry out a genetic analysis of cranial morphological variation in this species. In this analysis, novel DNA surveying techniques will be used to generate molecular markers whose variation will be correlated to individual differences in cranial morphology, measured through the use of 3D digitizing equipment. Quantitative trait loci contributing to individual differences in craniofacial morphology will then be identified using statistical methods tailored t complex pedigrees. Hypotheses about the developmental determinants of morphological variation will also be tested. This work will increase our sparse understanding of the genetic underpinnings of the mammalian craniofacial skeleton. It will also allow us to identify several genomic regions that affect the craniofacial skeleton. Some of these genomic regions may provide us with interesting candidate genes that will open up new research avenues for this model species. This work will also contribute to our understanding of the genetic and ontogenetic mechanisms for the evolution of craniofacial integration.

Public Health Relevance

The skull is a complex part of vertebrate anatomy, which develops through a complicated set of coordinated growth processes and performs a large number of functions during an organism's lifetime. By using a laboratory population of opossums with known pedigrees, this study will help us derive unique insights into the genetic underpinnings of craniofacial morphology that are relevant for human health conditions, such as the cleft palate.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31DE024944-01
Application #
8837341
Study Section
NIDR Special Grants Review Committee (DSR)
Program Officer
Frieden, Leslie A
Project Start
2014-09-01
Project End
2016-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Washington University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Grabowski, Mark; Porto, Arthur (2017) How many more? Sample size determination in studies of morphological integration and evolvability. Methods Ecol Evol 8:592-603
Melo, Diogo; Porto, Arthur; Cheverud, James M et al. (2016) Modularity: genes, development and evolution. Annu Rev Ecol Evol Syst 47:463-486
Porto, Arthur; Schmelter, Ryan; VandeBerg, John L et al. (2016) Evolution of the Genotype-to-Phenotype Map and the Cost of Pleiotropy in Mammals. Genetics 204:1601-1612
Porto, A; SebastiĆ£o, H; Pavan, S E et al. (2015) Rate of evolutionary change in cranial morphology of the marsupial genus Monodelphis is constrained by the availability of additive genetic variation. J Evol Biol 28:973-85