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.
Selected Publications
Newman DL, Hoffjan S, Bourgain C, Abney M, Nicolae RI, Profits ET, Grow MA, Walker K, Steiner L, Parry R, Reynolds R, McPeek MS, Cheng S, Ober C (2004) Are common disease susceptibility alleles the same in outbred and founder populations? Eur J Hum Genet, 12:949-54 PDF
Hoffjan S, Ostrovnaja I, Nicolae D, Newman DL, Nicolae R, Gangnon R, Steiner L, Walker K, Reynolds R, Greene D, Mirel D, Gern JE, Lemanske RF, Ober C (2004) Genetic variation in immunoregulatory pathways and atopic phenotypes in infancy. JACI 113:511-518 PDF
Hoffjan S, Nicolae D, Ober C (2004) Association studies for asthma and allergic disease: a comprehensive review of the literature. Resp Res 4:14-25 PDF
Bourgain C, Hoffjan S, Nicolae R, Newman D, Steiner L, Walker K, Reynolds R, Ober C, McPeek MS (2003) Novel case control test in a founder population identifies P-selectin as an atopy susceptibility locus. Am J Hum Genet 73:612-626 PDF
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 PDF
Newman DL, Abney M, Dytch H, Parry R, McPeek MS, Ober C (2003) Major loci influencing serum triglyceride levels on 2q14 and 9p21 localized by homozygosity-by-descent mapping in a large Hutterite pedigree. Hum Molec Genet 12:137-144 PDF
Hoffjan S, Ober C (2002) Present status on the genetic studies of asthma. Current Opinion in Immunology 14:709-717 PDF
Abney M, Ober C, McPeek MS (2002) Quantitative trait homozygosity mapping and empirical genome-wide significance in large complex pedigrees: fasting serum insulin levels in the Hutterites. Am J Hum Genet 70:920-934 PDF
Aldrich C, Wambebe C, Odama L, Di Rienzo A, Ober C (2002) Linkage disequilibrium and age estimates of a deletion polymorphism (1597DC) in HLA-G suggest non-neutral evolution. Hum Immunol 63:405-412 PDF
Jacob S, McClintock MK, Zelano B, Ober C (2002) Paternally-inherited HLA alleles are associated with women’s preferences for male odors. Nature Genet 30: 175-179 PDF
Aldrich CL, Stephenson MD, Karrison T, Odem RR, Branch DW, Scott JR, Schreiber JR, Ober C (2001) HLA-G genotypes and pregnancy outcome in couples with unexplained recurrent miscarriage. Molec Hum Reprod 7:1167-1172 PDF
Ober C, Abney M, McPeek MS (2001) Genetic dissection of complex traits in a founder population. Am J Hum Genet 69:1068-1079 PDF
Wu X, DiRienzo A, Ober C (2001) Population genetic study of single nucleotide polymorphisms in the interleukin 4 receptor a gene. Genes and Immunity 2:128-134 PDF
Ober C, Tsalenko A, Parry R, Cox NJ (2000) A second generation genome-wide screen for asthma susceptibility alleles in a founder population. Am J Hum Genet 67:1154-1162 PDF
Hunt JS, Jadhav L, Chu W, Geraghty DE, Ober C (2000) Soluble HLA-G circulates in maternal blood during pregnancy. Am J Obstet Gynecol 183:682-688 PDF
Ober C, Willadsen SA, Tsalenko A, Howard TD, Hoki DM, Daniel R, Newman DL, Wu X, parry R, Lester LA, Solway J, Blumenthal M, King RA, Xu J, Meyers DA, Bleecker ER, Cox NJ (2000) Variation in the interleukin 4 receptor a gene confers susceptibility to asthma and atopy in ethnically diverse populations. Am J Hum Genet 66:517-526 PDF
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 PDF
|