We have been studying common diseases in the Hutterites since 1994. The >1,000 Hutterites in our studies are related to each other through multiple lines of descent in a ~3,000-person, 14-generation pedigree. Quantitative and disease phenotypes are assessed in all individuals 6 years old and older during field trips to Hutterite colonies in South Dakota. Approximately 500 Hutterites were extensively phenotyped first in 1996-1997 and again in 2006-2009, providing longitudinal data for a subsample of individuals. We utilize a suite of analytical tools for our genetic studies that allow us to keep the entire pedigree intact and which correct for the relatedness between all members of the pedigree. Our laboratory is particularly interested in the sex-specific genetic architecture of human phenotypes, including physiological quantitative traits and disease status. Currently we have specific focuses on traits associated with asthma and allergy, diabetes and metabolic syndrome, and cardiovascular disease.
Using the extensive pedigree and life history data available on ~500 married Hutterite couples, we have demonstrated that measures of both male and female fertility are heritable in this population. We are currently performing genome-wide association studies to identify specific genes that influence fertility in the Hutterites, to elucide the functional effects of fertility-associated variation, and to demonstrate that fertility-associated genes are under selection.
In collaboration with Drs. Robert Lemanske and James Gern at the University of Wisconsin-Madison, we are investigating the genetics of immune responsiveness and asthma susceptibility in children at high risk for developing asthma. We are currently studying genes involved in the sex-specific IFN-γ response to rhinovirus and the regulation of miRNAs after RV infection in mononuclear cells.
We previously identified the non-classical HLA gene, HLA-G, as an asthma susceptibility gene. Susceptibility for asthma is determined by an interaction between the HLA-G genotype in the child and the asthma status of his/her mother. We are currently studying the effects of variation in this gene on gene expression and on peripheral levels of HLA-G protein during pregnancy, and characterizing the expression patterns and regulation in the bronchial epithelial cells in culture.
In collaboration with Drs. Joan Hunt and Margaret Petroff (Kansas University Medical Center), we are studying the role of genetic variation and expression patterns of HLA-G in preterm birth and preeclampsia. Patients receiving obstetrics care at the University of Chicago Hospital are enrolled in the Chicago Lying-In Pregnancy Program (CLIPP) biobank. DNA samples on the mother and child, and serum and plasma from the mother are stored for studies of pregnancy outcome.