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Arnold School study from Isle of Wight will examine growing field of 'epigenetic inheritance'
March 23, 2011
The Isle of Wight, Great Britain's largest island, is
home to the David Hide Allergy and Asthma Center
with which Arnold School researchers have
a major study from the NIH on allergic diseases.
Arnold School faculty members Dr. Wilfried Karmaus and Dr. Hongmei Zhang are part of an international team of researchers supported by a $2.8 million grant from the National Institutes of Health that will investigate the epigenetic inheritance of allergic diseases.
Karmaus is principal investigator of the RO1 study that also includes collaboration with scholars at Michigan State University, the University of Southampton in England, and the David Hide Allergy and Asthma Center on the Isle of Wight in the United Kingdom. He established this collaboration more than 10 years ago.
Epigenetic inheritance is a growing area of study because, despite advances in genetic testing and technology, a large number of diseases cannot be explained with genetic variants. Many scientists believe that epigenetic inheritance occurs from heritable alterations in which the DNA sequence itself remains unchanged.
"In the last 10 years, we learned that while our DNA only has a minor influence on our health, the lifestyles and exposures of our mothers and grandmothers may have a more substantial effect on our wellbeing," said Karmaus, a physician and the Arnold School's graduate director for epidemiology in the Department of Epidemiology and Biostatistics.
"Our asthma is programmed by our grand maternal and maternal smoking. Our own smoke exposure will not only hurt us but also that of our children and grandchildren. How can this be explained? There is a new perspective of research with burgeoning interest and research support – the epigenome. It is not the DNA, but the coating and packaging of the DNA (the epi-genome) that matter," Karmaus said.
"Epigenetic marks such as DNA methylation and histone modification lead to different activity of the DNA in different tissues – that is why our eyes, although they have the same DNA as our fingers, do not produce fingernails," he said. "But epigenetic marks also provide a memory of past exposure, social, physical, and biological. There are also transition periods in our life (pregnancy, adolescence, menopause) when the coating and packaging can change, either for the worse or for the better. That is what we need to understand."
The research subjects for the study include women born on Great Britain's Isle of Wight in 1989. The whole birth cohort with 1,456 participants was recently followed-up until the age of 18 years (90%). The new research will focus on the children of the 1989 birth cohort.
"First, we will filter about 450,000 epigenetic marks by testing their relation with allergy of the mothers to be, investigating the impact of pregnancy conditions, and determining the inheritance of epigenetic marks (cord blood)," he said.
"Finally, we will use this filtered set of epigenetic marks to test our prediction for developing allergic sensitization and eczema in these children," Karmaus said. "The epigenetic concept provides a unique opportunity to gain understanding not only on asthma and allergy, but also on obesity and diabetes. Of foremost interest, the epigenome does embrace a strong potential to explain the Weathering Hypothesis: the findings that African Americans still suffer from slavery and the segregation of their parents and grandparents."
Karmaus has a doctoral degree in medicine from the University of Hamburg in his native Germany. He also earned a master's degree in epidemiology from the University of North Carolina, Chapel Hill.
