Quantitative models play a central role in understanding the impact of adaptive processes on shaping patterns of standing genetic variation (the number and frequencies of mutations in natural populations, with special regard to those contributing to heritable variation in traits. Understanding how observations on patterns of such variation relate to models helps us design and interpret genetic association studies intended to map mutations underlying this heritable variation. This project will integrate two historically separate areas of theoretical genetics into a common simulation framework in order to study the dynamics of the adaptive evolution of complex traits (those affected by multiple genes and environmental influences) in order to understand the implications of such models for the interpretation of population genomic data and the design of association studies. The broader relevance of the research is related to association studies, which attempt to map mutations leading to traits like the risk of heritable disease.
Understanding the genetics of complex traits in natural populations requires an understanding of the role that evolutionary processes (mutation, natural selection, genetic drift, and demography) play in affecting the genetic composition of populations. Such an understanding depends heavily on theoretical models of the evolution of populations. Historically, population- and quantitative- genetic approaches to modeling the genetics of natural populations have developed largely in isolation. This proposal seeks to unify these two branches of theory in a common simulation framework in order to study the dynamics of the adaptive evolution of complex traits following environmental changes, with an eye towards understanding both population-genomic data and association study results in light of the model.
| Sanjak, Jaleal S; Sidorenko, Julia; Robinson, Matthew R et al. (2018) Evidence of directional and stabilizing selection in contemporary humans. Proc Natl Acad Sci U S A 115:151-156 |
| Rogers, Rebekah L; Shao, Ling; Thornton, Kevin R (2017) Tandem duplications lead to novel expression patterns through exon shuffling in Drosophila yakuba. PLoS Genet 13:e1006795 |
| Sanjak, Jaleal S; Long, Anthony D; Thornton, Kevin R (2017) A Model of Compound Heterozygous, Loss-of-Function Alleles Is Broadly Consistent with Observations from Complex-Disease GWAS Datasets. PLoS Genet 13:e1006573 |
| Sanjak, Jaleal S; Long, Anthony D; Thornton, Kevin R (2016) Efficient Software for Multi-marker, Region-Based Analysis of GWAS Data. G3 (Bethesda) 6:1023-30 |
| Rogers, Rebekah L; Cridland, Julie M; Shao, Ling et al. (2014) Landscape of standing variation for tandem duplications in Drosophila yakuba and Drosophila simulans. Mol Biol Evol 31:1750-66 |
