Our lab uses computational and statistical methods to uncover the mechanistic and evolutionary basis of functional genetic variation. This work integrates diverse datasets and conceptual frameworks from complex trait genetics and evolutionary genomics to test hypotheses about genome evolution and function.

Human Evolutionary Functional Genomics

Research over the last two decades has established that by consequence of ancient hybridization, contemporary non-African individuals possess approximately 2% Neanderthal ancestry, while Oceanic individuals possess an additional 2-4% Denisovan ancestry. By studying patterns and functional impacts of gene flow between modern and archaic humans, my research program seeks general insights into the genomic basis of phenotypic divergence. As an example of this approach, we previously leveraged RNA-seq data from modern humans to reveal functional characteristics of Neanderthal-inherited alleles. This work demonstrated that approximately one-quarter of persisting Neanderthal sequences exert measurable cis-regulatory effects on gene expression.  See a video about our latest publication on this topic here:

human karyotype

Embryonic Aneuploidy

Human reproduction is both inefficient and individually variable, despite its close link to fitness. Only approximately half of conceptions survive to term, mostly due to aneuploidy—the gain or loss of whole chromosomes. Working with collaborators from both academia and industry, we are investigating the molecular origins and functional consequences of such chromosome abnormalities. My past work on this topic demonstrated that in addition to aneuploidy arising during female meiosis, complex aneuploidies frequently occur during the initial embryonic mitoses, but are purged by selection around the time of embryonic genome activation. Some of these complex aneuploidies appear to arise by a mechanism of multipolar mitosis, in turn influenced by common maternal genetic variation at a quantitative trait locus spanning the centrosomal regulator PLK4. Building on these foundations, our future research will address the question of why certain chromosome abnormalities—including whole-chromosome aneuploidies, sub-chromosomal structural variants, and various mosaic forms—lead to preimplantation arrest, while others are tolerated or remain viable into late development.

Genomic Resource Development

Euphydryas gillettiiOur group is interested in collaborating to develop high-quality genomic resources for non-model species, thereby facilitating molecular approaches for studying ecology, evolution, and development in such systems. Previous work on this topic includes a study to test the utility of TruSeq synthetic long-read technology (formerly Moleculo) for de novo genome assembly, guiding expectations for future users. In a separate study, we developed an approach for simultaneous transcriptome assembly and single nucleotide polymorphism (SNP) marker discovery using multiplex RNA-seq. Applying this approach to an introduced population of the checkerspot butterfly Euphydryas gillettii, we demonstrated that demographic inference methods could accurately time a known historical bottleneck event. Photo credit: Carol Boggs.