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

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.

Loisel DA, Billstrand C, Murray K, Patterson K, Chaiworapongsa T, Romero R, Ober C

(Mar 2013) Molecular human reproduction 19(3):144-52 PMID:23002110 (Full Text)

Maternal microchimerism protects against the development of asthma.

Thompson EE, Myers RA, Du G, Aydelotte TM, Tisler CJ, Stern DA, Evans MD, Graves PE, Jackson DJ, Martinez FD, Gern JE, Wright AL, Lemanske RF, Ober C

(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.

Himes BE, Sheppard K, Berndt A, Leme AS, Myers RA, Gignoux CR, Levin AM, Gauderman WJ, Yang JJ, Mathias RA, Romieu I, Torgerson DG, Roth LA, Huntsman S, Eng C, Klanderman B, Ziniti J, Senter-Sylvia J, Szefler SJ, Lemanske RF, Zeiger RS, Strunk RC, Martinez FD, Boushey H, Chinchilli VM, Israel E, Mauger D, Koppelman GH, Postma DS, Nieuwenhuis MA, Vonk JM, Lima JJ, Irvin CG, Peters SP, Kubo M, Tamari M, Nakamura Y, Litonjua AA, Tantisira KG, Raby BA, Bleecker ER, Meyers DA, London SJ, Barnes KC, Gilliland FD, Williams LK, Burchard EG, Nicolae DL, Ober C, Demeo DL, Silverman EK, Paigen B, Churchill G, Shapiro SD, Weiss ST

(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.

Myers RA, Himes BE, Gignoux CR, Yang JJ, Gauderman WJ, Rebordosa C, Xie J, Torgerson DG, Levin AM, Baurley J, Graves PE, Mathias RA, Romieu I, Roth LA, Conti D, Avila L, Eng C, Vora H, LeNoir MA, Soto-Quiros M, Liu J, Celedón JC, Farber HJ, Kumar R, Avila PC, Meade K, Serebrisky D, Thyne S, Rodriguez-Cintron W, Rodriguez-Santana JR, Borrell LN, Lemanske RF, Bleecker ER, Meyers DA, London SJ, Barnes KC, Raby BA, Martinez FD, Gilliland FD, Williams LK, Burchard EG, Weiss ST, Nicolae DL, Ober C

(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.

Ding D, Scott NM, Thompson EE, Chaiworapongsa T, Torres R, Billstrand C, Murray K, Dexheimer PJ, Ismail M, Kay H, Levy S, Romero R, Lindheimer MD, Nicolae DL, Ober C

(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.

Levin AM, Mathias RA, Huang L, Roth LA, Daley D, Myers RA, Himes BE, Romieu I, Yang M, Eng C, Park JE, Zoratti K, Gignoux CR, Torgerson DG, Galanter JM, Huntsman S, Nguyen EA, Becker AB, Chan-Yeung M, Kozyrskyj AL, Kwok PY, Gilliland FD, Gauderman WJ, Bleecker ER, Raby BA, Meyers DA, London SJ, Martinez FD, Weiss ST, Burchard EG, Nicolae DL, Ober C, Barnes KC, Williams LK

(Nov 2012) The Journal of allergy and clinical immunology PMID:23146381

The ABO blood group is a trans-species polymorphism in primates.

Ségurel L, Thompson EE, Flutre T, Lovstad J, Venkat A, Margulis SW, Moyse J, Ross S, Gamble K, Sella G, Ober C, Przeworski M

(Nov 2012) Proceedings of the National Academy of Sciences of the United States of America 109(45):18493-8 PMID:23091028 (Full Text)

Estimating the human mutation rate using autozygosity in a founder population.

Campbell CD, Chong JX, Malig M, Ko A, Dumont BL, Han L, Vives L, O'Roak BJ, Sudmant PH, Shendure J, Abney M, Ober C, Eichler EE

(Nov 2012) Nature genetics 44(11):1277-81 PMID:23001126 (Full Text)

Genome-wide association studies of asthma indicate opposite immunopathogenesis direction from autoimmune diseases.

Li X, Ampleford EJ, Howard TD, Moore WC, Torgerson DG, Li H, Busse WW, Castro M, Erzurum SC, Israel E, Nicolae DL, Ober C, Wenzel SE, Hawkins GA, Bleecker ER, Meyers DA

(Oct 2012) The Journal of allergy and clinical immunology 130(4):861-8.e7 PMID:22694930 (Full Text)

A population-based study of autosomal-recessive disease-causing mutations in a founder population.

Chong JX, Ouwenga R, Anderson RL, Waggoner DJ, Ober C

(Oct 2012) American journal of human genetics 91(4):608-20 PMID:22981120 (Full Text)

Genome-wide ancestry association testing identifies a common European variant on 6q14.1 as a risk factor for asthma in African American subjects.

Torgerson DG, Capurso D, Ampleford EJ, Li X, Moore WC, Gignoux CR, Hu D, Eng C, Mathias RA, Busse WW, Castro M, Erzurum SC, Fitzpatrick AM, Gaston B, Israel E, Jarjour NN, Teague WG, Wenzel SE, Rodríguez-Santana JR, Rodríguez-Cintrón W, Avila PC, Ford JG, Barnes KC, Burchard EG, Howard TD, Bleecker ER, Meyers DA, Cox NJ, Ober C, Nicolae DL

(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.

Jassem RM, Shani WS, Loisel DA, Sharief M, Billstrand C, Ober C

(Aug 2012) Human immunology 73(8):811-7 PMID:22651916 (Full Text)

Genome-wide association study identifies candidate genes for male fertility traits in humans.

Kosova G, Scott NM, Niederberger C, Prins GS, Ober C

(Jun 2012) American journal of human genetics 90(6):950-61 PMID:22633400 (Full Text)

Accurate imputation of rare and common variants in a founder population from a small number of sequenced individuals.

Uricchio LH, Chong JX, Ross KD, Ober C, Nicolae DL

(May 2012) Genetic epidemiology 36(4):312-9 PMID:22460724

Resequencing candidate genes implicates rare variants in asthma susceptibility.

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

(Feb 2012) American journal of human genetics 90(2):273-81 PMID:22325360 (Full Text)

IFNG genotype and sex interact to influence the risk of childhood asthma.

Loisel DA, Tan Z, Tisler CJ, Evans MD, Gangnon RE, Jackson DJ, Gern JE, Lemanske RF, Ober C

(Sep 2011) The Journal of allergy and clinical immunology 128(3):524-31 PMID:21798578 (Full Text)

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Torgerson DG, Ampleford EJ, Chiu GY, Gauderman WJ, Gignoux CR, Graves PE, Himes BE, Levin AM, Mathias RA, Hancock DB, Baurley JW, 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 MU, 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, Sienra-Monge JJ, del Rio-Navarro B, Deichmann KA, Heinzmann A, Wenzel SE, Busse WW, Gern JE, Lemanske RF, Beaty TH, Bleecker ER, Raby BA, Meyers DA, London SJ, Gilliland FD, Burchard EG, Martinez FD, Weiss ST, Williams LK, Barnes KC, Ober C, Nicolae DL

(Sep 2011) Nature genetics 43(9):887-92 PMID:21804549 (Full Text)

Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19p13.

Çalışkan 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

(Apr 2011) Human molecular genetics 20(7):1285-9 PMID:21212097 (Full Text)

Gene-environment interactions in human disease: nuisance or opportunity?

Ober C, Vercelli D

(Mar 2011) Trends in genetics : TIG 27(3):107-15 PMID:21216485 (Full Text)

The CFTR Met 470 allele is associated with lower birth rates in fertile men from a population isolate.

Kosova G, Pickrell JK, Kelley JL, McArdle PF, Shuldiner AR, Abney M, Ober C

(Jun 2010) PLoS genetics 6(6):e1000974 PMID:20532200 (Full Text)

PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice.

Baudat F, Buard J, Grey C, Fledel-Alon A, Ober C, Przeworski M, Coop G, de Massy B

(Feb 2010) Science (New York, N.Y.) 327(5967):836-40 PMID:20044539

Colloquium papers: Heritability of reproductive fitness traits in a human population.

Kosova G, Abney M, Ober C

(Jan 2010) Proceedings of the National Academy of Sciences of the United States of America 107 Suppl 1:1772-8 PMID:19822755 (Full Text)

Sex-specific genetic architecture of human disease.

Ober C, Loisel DA, Gilad Y

(Dec 2008) Nature reviews. Genetics 9(12):911-22 PMID:19002143 (Full Text)

Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function.

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

(Apr 2008) The New England journal of medicine 358(16):1682-91 PMID:18403759 (Full Text)

High-resolution mapping of crossovers reveals extensive variation in fine-scale recombination patterns among humans.

Coop G, Wen X, Ober C, Pritchard JK, Przeworski M

(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.

Tan Z, Randall G, Fan J, Camoretti-Mercado B, Brockman-Schneider R, Pan L, Solway J, Gern JE, Lemanske RF, Nicolae D, Ober C

(Oct 2007) American journal of human genetics 81(4):829-34 PMID:17847008 (Full Text)

The sex-specific genetic architecture of quantitative traits in humans.

Weiss LA, Pan L, Abney M, Ober C

(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.

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

(Feb 2005) American journal of human genetics 76(2):349-57 PMID:15611928 (Full Text)

Paternally inherited HLA alleles are associated with women's choice of male odor.

Jacob S, McClintock MK, Zelano B, Ober C

(Feb 2002) Nature genetics 30(2):175-9 PMID:11799397

Mononuclear-cell immunisation in prevention of recurrent miscarriages: a randomised trial.

Ober C, Karrison T, Odem RR, Barnes RB, Branch DW, Stephenson MD, Baron B, Walker MA, Scott JR, Schreiber JR

(Jul 1999) Lancet 354(9176):365-9 PMID:10437864