Chair, Department of Human Genetics
Department of Obstetrics and Gynecology
Committee on Genetics, Genomics, and Systems Biology
B.A., George Washington University, 1972
Fax: (773) 834-0505
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. Medicine on the Midway article
Our studies of fertility focus on HLA-region genes, in particular the non-classical HLA-G gene. These studies have indicated that multiple HLA genes influence different aspects of fertility, and that variation in the promoter and 3'UTR of HLA-G affects expression. We recently completed a genome-wide association study for fertility in the Hutterites that identified novel genes that influence reproductive traits in men and women.
Our studies of common diseases focus on phenotypes 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 >30 quantitative traits that are associated with common diseases, some with sex-specific effects. We also 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 or with sex-specific effects to influence these phenotypes.
The maternal HLA-G 1597ΔC null mutation is associated with increased risk of pre-eclampsia and reduced HLA-G expression during pregnancy in African-American women.
Maternal microchimerism protects against the development of asthma.
(Feb 2013) The Journal of allergy and clinical immunology PMID:23434286
Integration of Mouse and Human Genome-Wide Association Data Identifies KCNIP4 as an Asthma Gene.
(2013) PloS one 8(2):e56179 PMID:23457522
Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans.
(Dec 2012) The Journal of allergy and clinical immunology 130(6):1294-301 PMID:23040885
Increased protein-coding mutations in the mitochondrial genome of African American women with preeclampsia.
(Dec 2012) Reproductive sciences (Thousand Oaks, Calif.) 19(12):1343-51 PMID:22902742
A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations.
(Nov 2012) The Journal of allergy and clinical immunology PMID:23146381
The ABO blood group is a trans-species polymorphism in primates.
Estimating the human mutation rate using autozygosity in a founder population.
Genome-wide association studies of asthma indicate opposite immunopathogenesis direction from autoimmune diseases.
A population-based study of autosomal-recessive disease-causing mutations in a founder population.
Genome-wide ancestry association testing identifies a common European variant on 6q14.1 as a risk factor for asthma in African American subjects.
(Sep 2012) The Journal of allergy and clinical immunology 130(3):622-629.e9 PMID:22607992
HLA-G polymorphisms and soluble HLA-G protein levels in women with recurrent pregnancy loss from Basrah province in Iraq.
Genome-wide association study identifies candidate genes for male fertility traits in humans.
Accurate imputation of rare and common variants in a founder population from a small number of sequenced individuals.
(May 2012) Genetic epidemiology 36(4):312-9 PMID:22460724
Resequencing candidate genes implicates rare variants in asthma susceptibility.
IFNG genotype and sex interact to influence the risk of childhood asthma.
Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.
Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19p13.
Gene-environment interactions in human disease: nuisance or opportunity?
The CFTR Met 470 allele is associated with lower birth rates in fertile men from a population isolate.
PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice.
(Feb 2010) Science (New York, N.Y.) 327(5967):836-40 PMID:20044539
Colloquium papers: Heritability of reproductive fitness traits in a human population.
Sex-specific genetic architecture of human disease.
Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function.
High-resolution mapping of crossovers reveals extensive variation in fine-scale recombination patterns among humans.
(Mar 2008) Science (New York, N.Y.) 319(5868):1395-8 PMID:18239090
Allele-specific targeting of microRNAs to HLA-G and risk of asthma.
The sex-specific genetic architecture of quantitative traits in humans.
(Feb 2006) Nature genetics 38(2):218-22 PMID:16429159
Fine mapping and positional candidate studies identify HLA-G as an asthma susceptibility gene on chromosome 6p21.
Paternally inherited HLA alleles are associated with women's choice of male odor.
(Feb 2002) Nature genetics 30(2):175-9 PMID:11799397
Mononuclear-cell immunisation in prevention of recurrent miscarriages: a randomised trial.
(Jul 1999) Lancet 354(9176):365-9 PMID:10437864