Scientists at Johns Hopkins are calling for simultaneous evaluation of both genetic and epigenetic information in the search to understand contributors to such common diseases as cancer, heart disease and diabetes.
Writing in the August issue of Trends in Genetics, available now online, the scientists provide a framework for systematically incorporating epigenetic information into traditional genetic studies, something they say will be necessary to understand the genetic and environmental factors behind common diseases.
"Epigenetics doesn't underlie all human disease, but we definitely need to develop the technology to figure out when and where epigenetic changes do influence health and disease," says Andrew Feinberg, M.D., King Fahd Professor of Medicine.
Much as the genetic sequence is passed from parent to child, epigenetic "marks" that sit on our genes are also inherited. These "marks," usually small methyl groups, are attached to genes' backbones and convey information, such as identifying which parent the gene came from. The marks also normally turn genes on or off. But just as changes in DNA sequences can cause diseases such as cancer, gain or loss of epigenetic marks can, too.
To date, only small, targeted regions of DNA have been analyzed for accompanying epigenetic marks. But the Hopkins researchers say now is the time to begin studying epigenetics on the same mammoth scale used to probe the sequence of creatures' genetic building blocks.
But to establish what's "normal," epigenetically speaking, for the entire genome, Feinberg says scientists will need new technologies to quickly, accurately and inexpensively determine which epigenetic marks are present and where they are, much as "high-throughput" technology revolutionized genetics.
"That kind of power is needed to create comprehensive epigenetic information, but right now the technology doesn't exist," says Feinberg, who pioneered the study of epigenetics in cancer. "Developing that technology, and the necessary statistical approaches to analyze the data, will require a major collaborative effort and should be first on the to-do list."
A first step toward these goals is the new, multi-institutional Center for the Epigenetics of Common Human Disease, which Feinberg is directing. With a $5 million, five-year grant from the National Human Genome Research Institute and the National Institute of Mental Health, Center researchers will develop the tools they need and then begin systematically examining the epigenetics of autism and bipolar disorder. But a broader effort will be necessary, Feinberg says.
"Just as geneticists are probing samples to identify genotypes and haplotypes [lengthy genetic sequences that are inherited in blocks], we need to examine multiple samples from different tissues and different people to establish 'epigenotypes,'" says Feinberg. "Only by superimposing genetic and epigenetic information will we get a complete picture of how genes' functions are affected in healthy people and in those with particular diseases."
Feinberg and co-authors Hans Bjornsson and epidemiologist Daniele Fallin say current attempts to establish genetic contributors to common diseases will fall short without equivalent epigenetic information.