Research Description

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.

Selected Publications

• 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
• Jacob S, McClintock MK, Zelano B, Ober C (2002) Paternally-inherited HLA alleles are associated with women’s preferences for human odors. Nat Genet 30: 175-179
• 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
• Weiss LA, Pan L, Abney M, Ober C (2006) The sex-specific genetic architecture of quantitative traits in humans. Nat Genet 38:218-222
• 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. Amer J Hum Genet 81:829-834
• 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
• Ober C, Loisel DA, Gilad Y (2008) Sex-specific genetic architecture of human disease. Nat Rev Genet 9:911-92215.
• 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. New Eng J Med 358: 1682-1691
• Kosova G, Abney M, Ober C (2010) Heritability of reproductive fitness traits in a human population. PNAS 107 Supp 1:1772-8, E-pub 10/12/2009
• Baudat F, Buard J, Grey C, Fledel-Alon A, Ober C, Przeworski M, Coop G, de Massy B (2010) The zinc finger protein PRDM9 is a major determinant of meiotic recombination hotspots. Science 327:836-40
• Kosova G, Pickrell JK, Kelley JL, McArdle PF, Shuldiner AR, Abney M, Ober C (2010) The CFTR Met 470 allele is associated with lower birth rates in fertile men from a population isolate. PLoS Genet 6:e1000974
• Calişkan M, Chong JX, Uricchio L, Anderson R, Chen P, Sougnez C, Garimella K, Gabriel SB, Depristo MA, Shakir K, Matern D, Das S, Waggoner D, Nicolae DL, Ober C (2011) Exome sequencing reveals a novel mutation for autosomal recessive nonsyndromic mental retardation in the TECR gene on chromosome 19p13. Hum Molec Genet 20:1285-1289
• Torgerson DG, Ampleford EJ, Chiu GY, Gauderman WJ, Gignoux CR, Graves PE, Himes BE, Levin AM, Mathias RA, Hancock DB, Baurley J, Eng C, Stern DA, Celedón JC, Rafaels N, Capurso D, Conti DV, Roth LA, Soto-Quiros M, Togias A, Li X, Myers RA, Romieu I, Van den Berg DJ, Hu D, Hansel NN, Hernandez RD, Israel E, Salam MT, Galanter J, Avila PC, Avila L, Rodriquez-Santana JR, Chapela R, Rodriguez-Cintron W, Diette GB, Adkinson NF, Abel RA, Ross KD, Shi M, Faruque WMU, Dunston GM, Watson HR, Mantese VJ, Ezurum SC, Liang L, Ruczinski I, Ford JG, Huntsman S, Chung KF, Vora H, Li X, Calhoun WJ, Castro M, Sierra-Monge JJ, del Rio-Navarro B, Deichmann KA, Heinzmann A, Wenzel SE, Busse WW, Gern JE, Lemanske Jr. RF, Beaty TH, Bleecker ER, Raby BA, Meyers DA, London SJ, Gilliland FD, Burchard EG, Martinez FD, Weiss ST, Williams LK, Barnes KD, Ober C, Nicolae DL (2011) Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. Nat Genet 43:887-892
• Loisel DA, Tan Z, Tisler CJ, Evans MD, Gangnon RE, Jackson DJ, Gern JE, Lemanske RF, Ober C (2011) IFNG genotype and sex interact to influence risk of childhood asthma. J Allergy Clin Immunol 128:524-531
• Ober C, Vercelli D (2011) Gene-environment interactions in human disease: nuisance or opportunity? Trends in Genetics 27:107-115
• Torgerson DG, Capurso D, Mathias RA, Graves PE, Hernandez RD, Beaty TH, Bleecker ER, Raby BA, Meyers DA, Barnes KC, Weiss ST, Martinez FD, Nicolae DL, Ober C (2012) Resequencing candidate genes implicates rare variants in asthma susceptibility. Amer J Hum Genet, in press
• Uricchio LH, Chong JX, Ross KD, Ober C, Nicolae DL (2012) Accurate imputation of rare and common variants in a founder population from a small number of sequenced individuals. Genet Epidem, in press