- Professor and Chair, Dept. of Human Genetics
Department of Human Genetics
The University of Chicago
920 E. 58th St., CLSC 507C
Chicago, IL 60637
Phone: 773 834 0735
Fax: 773 834 0735
The major research objectives of my laboratory are to identify genes that influence complex phenotypes, to understand their evolutionary history, and to elucidate how variation in these genes influences function. Our laboratory focuses on phenotypes related to fertility and to common diseases, and are conducted in a founder population, the Hutterites, and in outbred patient populations.
Our studies of fertility have focused primarily on HLA-region genes, including the non-classical HLA-G gene and the olfactory receptor genes in the extended class I region. These studies have indicated that genes in different HLA regions influence different components of fertility. For example, maternal-fetal compatibility for alleles at the class II locus, HLA-DRB1, is associated with reduced fecundity, maternal-fetal compatibility for alleles at the class I locus, HLA-B, is associated with sporadic fetal loss, while specific variants in the promoter and coding region of HLA-G are associated with both sporadic and recurrent pregnancy loss. We have recently completed a genome-wide screen for non-HLA loci that influence fecundity in the Hutterites and are initiating fine mapping and positionally cloning studies in selected regions.
Our studies of common diseases focus mainly on phenotypes that are associated with asthma and heart disease. In collaboration with Mary Sara McPeek and Mark Abney, we developed novel methods for quantitative trait locus (QTL) mapping in the Hutterites, and have studied >25 quantitative traits that are associated with common diseases. Fine mapping and positional cloning studies are underway for some of these traits. In addition, we have identified three chromosomal regions that house asthma-susceptibility loci (on 5p, 6p, and 19q) that are currently the focus of positional cloning studies in our laboratory in both the Hutterites and families ascertained as part of the Collaborative Study on the Genetics of Asthma (CSGA). Lastly, we collaborate with investigators at the University of Wisconsin – Madison on the Childhood Origins of ASThma (COAST) Study. This is a prospective cohort study of children at high risk for developing asthma and allergy, who are followed from birth onward. Our laboratory is genotyping the children in this study and their parents to identify genetic variation that influences the development of the immune system in the first year of life and the subsequent development of asthma and atopic disease, as well as variation that interacts with early life environmental exposures to influence these phenotypes. We have recently identified variation at several candidate loci with direct effects on first year immune and atopic phenotypes, and that interact with daycare exposure in the first year of life to influence the developing immune system.