This topic specifically targets developing a deep and diverse understanding of genetic maps and recombination within and between species, which is what our proposal intends to study. Project Title: Fine-scale recombination rate variation within and between Drosophila species. Over the past two decades the NIH, NSF, USDA, and DOE have invested billions of dollars into genomic sequencing. These genome projects have given us new insight into the biological basis of disease, led to the production of new diagnostic tools, and recently contributed to the development of high throughput resequencing technologies (HTseq) that are revolutionizing biomedical research. With these recent technological breakthroughs, researchers can resequence the full genome of any individual at costs approaching a """"""""thousand dollar genome."""""""" The resultant data will usher in an era of """"""""personalized medicine"""""""" by enhancing our understanding of what makes individuals unique, helping physicians tailor treatments to individuals, identifying new genetic determinants for the susceptibility, etiology, and pathogenesis of many diseases, and generally giving us a deeper understanding of biology. Making sense of this new found wealth of genomic data is the new challenge. Key unsolved questions are where does the biologically relevant variation reside and what are the structural, evolutionary, and genetic processes shaping this variation? Meiotic recombination lies at the nexus of these two questions. Genetic mapping remains one of our primary tools for uncovering meaningful associations between genetic and phenotypic variation. In most eukaryotes, recombination is critical for ensuring proper chromosome segregation, facilitating DNA repair, and providing a basis for genetic diversity. Recombination, by breaking up linkage relationships among loci, also allows different genomic regions to have different evolutionary histories. The results of this multi-PI, 2-year project will fill in a gap in our basic knowledge of one of the fundamental parameters in biology: recombination. The collection of genetic maps produced by this project will provide an unprecedented insight how recombination varies within and between populations and among species. Our data will be a critical resource for the large and heterogeneous scientific community interested in population genetics and whole genome association studies.
While whole genome association studies (WGA) have be successful in identifying a number of new loci associated with diseases and complex traits, such as diabetes, these loci only explain a fraction of the heritability of these traits. WGA studies, however, assume that recombination rates are invariant among individuals within species, an assumption that is either unjustified or untrue. The results of our comprehensive study on how recombination rates vary within populations of Drosophila - a commonly used model system for association studies - will reshape how human WGA are performed and lay out the foundation for a new generation of WGA models and tools.
