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 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, 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 to influence these phenotypes.
Selected Publications
Ober C, Tan Z, Sun Y, Possick JD, Pan L, Nicolae R, Radford S, Parry RR, Heinzmann A, Deichmann KA, Lester LA, Gern JE, Lemanske RF, Nicolae DL, Elias JA, Chupp GL (2008) Variation in the CHI3L1 gene influences serum YKL-40 levels, asthma risk, and lung function. NEJM 358: 1682-1691 PDF
Coop G, Wen X, Ober C, Pritchard JK, Przeworski M (2008) High-resolution mapping of crossovers reveals extensive variation in fine-scale recombination patterns among humans. Science 319: 1395-1398 PDF
Gallego Romero I, Ober C (2008) CFTR mutations and reproductive outcomes in a population isolate. Human Genet 122:583-588 PDF
Tan Z, Randall G, Fan J, Camoretti-Mercado B, Brockman-Schneider R, Pan L, Solway J, Gern JE, Lemanske RF, Nicolae D, Ober C (2007) Allele-specific targeting of microRNAs to HLA-G and risk for asthma. Am J Hum Genet 81:829-834
Pluzhnikov A, Nolan DK, Tan Z, McPeek MS, Ober C (2007) Correlation of intergenerational family sizes suggests a genetic component to reproductive fitness. Am J Hum Genet 81:165-169
Pan L, Ober C, Abney M (2007) Heritability estimates of sex specific effects on human quantitative traits. Genet Epidem 31:338-347
Ober C, Billstrand C, Kuldanek S, Tan Z (2006) The miscarriage associated HLA-G -725G allele is influences transcription rates in JEG-3 cells. Hum Reprod 21:1743-1748
Weiss LA, Pan L, Abney M, Ober C (2006) The sex-specific genetic architecture of quantitative traits in humans. Nature Genet 38:218-222
Ober C, Thompson EE (2005) Rethinking models of asthma genetics: role of environmental modifiers. Current Opinion in Immunology 17:1-9
Hunt JS, Petroff MG, McIntire R, Ober C (2005) HLA-G and immune tolerance in pregnancy. FASEB J 19:681-693
Nicolae D, Cox NJ, Lester LA, Schneider D, Tan Z, Billstrand C, Kuldanek S, Donfack J, Kogut P, Patel NM, Goodenbour J, Howard T, Wolf R, Koppelman GH, White SR, Parry R, Postma DS, Meyers D, Bleecker ER, Hunt JS, Solway J, Ober C (2005) Fine mapping and positional candidate studies identify HLA-G as an asthma susceptibility gene on chromosome 6p21. Amer J Hum Genet 76:349-357
Ober C, Aldrich CL, Chervoneva I, Billstrand C, Rahimov F, Gray HL, Hyslop T (2003) Variation in the HLA-G promoter region influences miscarriage rates. Am J Hum Genet 72: 1425-1435
Jacob S, McClintock MK, Zelano B, Ober C (2002) Paternally-inherited HLA alleles are associated with women’s preferences for human odors. Nature Genet 30: 175-179
Ober C, Abney M, McPeek MS (2001) Genetic dissection of complex traits in a founder population. Am J Hum Genet 69:1068-1079
Ober C, Karrison T, Odem RR, Barnes RB, Branch DW, Stephenson MD, Baron B, Walker MA, Scott JR, Schreiber JR (1999) Mononuclear-cell immunisation in the prevention of recurrent miscarriage:a randomised trial. Lancet 354:365-369
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