Solving epigenetic mysteries focus of Carole Ober's work

AAAS Fellow Carole Ober's research is on epigenetics and how genes express themselves under the influence of various environmental and behavioral factors.

Carole Ober's first love as a student was anthropology, and her enduring curiosity about the lives of real people in their cultural settings has helped propel her to the heights of her present field, human genetics.

Recently turning her focus toward epigenetics—how genes express themselves under the influence of various environmental and behavioral factors—Ober, a AAAS fellow, is leveraging her long history of field research with the Hutterites of the Upper Midwest in hopes of solving some of the mysteries she has explored in the two main areas of inquiry she has pursued over her career, asthma and fertility.

The chairman of the University of Chicago's Dept. of Human Genetics, Ober drifted into genetics through a series of tangents, corrections and fortuitous connections in graduate school at Northwestern University in Evanston, Ill., where she studied anthropology, and in subsequent research and teaching positions at N.U., including work she did at the university's medical complex in Chicago. In 1988, she moved to the U. of C. as a fully-fledged human geneticist.

"I never had a life plan," she said. "I was driven by my love of research."

Ober's early work focused on human leukocyte antigens (HLA), a gene family or "locus" that helps the body distinguish its own proteins from foreign ones.

"At the time, there wasn't a lot of genetics to look at, so we focused on HLA," recalls Ober, who got her Ph.D. in 1979. "The first half of my career focused on understanding the role of HLA in pregnancy. The mystery was, how can the mom carry a fetus with HLA from the dad, and not reject it as foreign?"

That's where the Hutterites came in. An ethno-religious group with the same Central European Anabaptist roots as the Amish, and a similar dedication to living apart from the modern urban world, the Hutterites typically marry one another. They're all descended from about 90 people and are extraordinarily homogeneous, Ober said.

A popular theory among fertility experts in the 1980s held that similarities in parental HLA types were an impediment to fertility. Ober's studies found that similar HLA in Hutterite parents did in fact hamper their fertility, but not much. "They still had 10 kids, but it took them longer," she said, both because of increased incidence of miscarriage, and also longer stretches between pregnancies.       

HLA also plays a role in asthma. "The HLA-G gene, which is important in pregnancy — it makes the mother tolerant of the baby — is also a marker of the asthmatic lung. I've noticed that if an important set of genes is found in asthma research, soon, I'll start seeing that same set of genes in papers in a fertility context. I probably wouldn't see that if I weren't straddling both fields."

Ober is also interested in the effects of a mother's asthma while she's pregnant on subsequent asthma in her children. "One of the most important risk factors for asthma in a child is whether his mother has asthma. It's not genetic, at least not entirely. Does that unique environment in pregnancy set the child up to be predisposed?\" she said.

Ober still goes to South Dakota to work with the Hutterites nearly every year, with students and other researchers, often setting up a clinic in a school gymnasium, where the team does a raft of clinical tests on members of the community, who appreciate getting expensive medical exams for free, she said. Also, the Hutterites have high rates of asthma, and they're concerned about that, she said.

"I love to take my students out into the field. It's so important for them to meet the people whose cells and DNA they're studying. It puts a whole different slant on how they think about the research. It makes it so much more personal," she said.

Ober goes to northeastern Indiana now as well, to work with the Amish, who come from the same part of Europe as the Hutterites, but spend their lives closer to the land and their animals. (The Hutterites are traditional and even isolated socially, but their farms are industrialized, and not near their homes, Ober said.) The Amish have negligible rates of asthma, and Ober is comparing the two groups, exploring the possibility that the microbes the Amish are exposed to in their more natural daily lives are protective against asthma .

Ober is also heading up one of several research teams nationwide that will explore the interplay of genetic and other influences on preterm birth, with a $10 million grant from the March of Dimes. Her particular consortium will bring together researchers from the University of Chicago, Northwestern University Feinberg School of Medicine in Chicago, and Duke University School of Medicine in Raleigh, N.C.

The question her team will be asking on this project, Ober said, is, \"How does your genetic makeup predispose your response to your environment, so that when you are placed in that environment, you are likely to have a preterm birth?"

Ober continues her work with asthma, including an exploration of the epigenetic association with asthma in children who get very sick with rhinovirus, which causes the common cold. Asthma has been on the rise in America, she said.

Ober is determined to solve some epigenetic mysteries before she retires.

"In both preterm birth and asthma studies, I would love to come up with at least one if not multiple great examples of how there is an environmental impact on gene regulation that is modified by your genotype and predictive of disease — something that is translatable into clinical disease or preterm birth," Ober said. "I think we'll get there."

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