Genetic variation at the level of DNA sequence mediates much of the phenotypic diversity that exists in nature, both within and between species, including humans. My lab uses the tools of computational and statistical human genetics to answer questions about how germline and somatic evolution shape 1) genome function and 2) reproduction and development. Our work spans diverse systems but is unified around the goal of developing methods for elucidating the evolutionary forces that impact our genomes across scales of biological organization. Importantly, much of the phenotypic variation in nature traces not to differences in amino acid sequences, but to regulatory variation influencing transcription and splicing of RNA. I will describe my lab’s recent work generating and analyzing a large gene expression dataset from globally diverse human individuals, toward a more complete view of the mechanisms driving gene expression diversity and evolution within our species. In addition to the evolutionary processes operating across generations, my lab is also interested in the recurrent forces of natural selection that shape human development. For example, it is estimated that less than half of all human conceptions survive to birth, primarily due to chromosome mis-segregation during meiosis and mitosis. I will describe unpublished work repurposing clinical genetic testing data from in vitro fertilized embryos to understand the genetic basis of variation in human chromosome abnormalities.
