Most traits, including complex diseases like diabetes, psychiatric disorders and cardiovascular disease, have a strong genetic component. However, how individual alleles affect trait expression may depend on genotypes at other loci, or on aspects of the environment. The proposed research seeks to elucidate the extent and nature of conditionally functional mutations in the determination of complex traits, using the developmental and genetic model organism C. elegans. This worm is amenable to high- throughput, automated phenotyping methodologies, which permit sufficient replication to detect the potentially subtle effects of natural allelic variants. Thus, the work leverages the resources in an experimental model system to ask questions about the functional consequences of natural genetic variation. By working at the interface of quantitative and model system genetics, this research aims to improve our understanding of complex trait architecture as well as provide new insight into the genetic and developmental mechanisms that lie between genotype and phenotype.

Public Health Relevance

Complex diseases like diabetes, psychiatric disorders and cardiovascular disease carry genetic risks, and these risks have been hypothesized to have increased under modern environments. This work examines development in a small nematode worm, C. elegans, to model how complicated biological processes are determined by interactions between genes and between genes and the environment.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
5R35GM119744-02
Application #
9349541
Study Section
Special Emphasis Panel (ZRG1-CB-E (50)R)
Program Officer
Krasnewich, Donna M
Project Start
2016-09-08
Project End
2021-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
2
Fiscal Year
2017
Total Cost
$371,742
Indirect Cost
$130,103
Name
Georgia Institute of Technology
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30318
Campbell, Richard F; McGrath, Patrick T; Paaby, Annalise B (2018) Analysis of Epistasis in Natural Traits Using Model Organisms. Trends Genet 34:883-898