Human genetics & reproductive biology
The Conrad lab develops and applies novel methods for human genetic analysis, which span the cycle from variation discovery, statistical assessment of variation, and functional characterization of putative disease variants. Our computational methods address fundamental problems and have broad applicability to human and non-human systems. Our applied epidemiological work is targeted specifically to reproductive disorders and rare disease. Our experimental work is used to functionally characterize patient-derived mutations, study the cell and genome biology of mammalian germ cells, and develop better tools for the diagnosis and treatment of disease.
Genomic variation
We have a long track record of participation in large-scale international consortia mapping the location and consequences of human variation, such as the Structural Variation Consortium, 1000 Genomes Project, and most recently, as a funded member of the Genotype Tissue Expression Project (GTEx). As part of GTEx we developed methods for studying the functional impact of CNVs on gene expression, methods to formally evaluate the statistical significance of mutations identified in n=1 cases of disease, and are currently using the GTEx resource to make full-body maps of somatic mutations.
Human reproduction
A primary goal of our research is to develop genome sequencing into a useful diagnostic tool in the management of infertility. This requires a knowledgebase of bona fide infertility genes and disease-causing variants. In partnership with Dr. Ki Aston of the University of Utah, we have organized an international consortium to identify genetic causes of male infertility, GEMINI, consisting of a dozen PIs on four continents, who collectively see over 15,000 patients a year. Funded by a grant from the NIH, we have recruited over 3,000 subjects into the GEMINI study since 2014. We pursue interesting findings in the laboratory using experiments in cell lines and animals. We also apply the same experimental tools to study the genomics of healthy reproduction in mammals.
Single cell genomics
There are likely some genetic forms of infertility that have yet to be described due to the difficulty of making measurements on single cells and scarce cell populations. Thus, single-cell genomics is an essential technology for the study of reproductive cell biology. We develop and apply single-cell methods for characterizing genetic defects from tissue of patients and model organisms with unexplained infertility, with the long-term goal of translating our approaches into improved diagnosis in the clinical and research environments.