Hopkins studies DNA link to the epigenome

Genetic studies are indispensable tools for developing a comprehensive understanding of diseases, particularly cancer and psychiatric illnesses. Many investigators compare the genetic backgrounds of healthy and sick populations to identify the proclivity of specific factors in the genome to certain diseases.

Until recently, however, researchers have not had a reliable way to compare patterns in the epigenome. Also important for understanding diseases, the epigenome consists of chemical compounds that surround the DNA and control which genetic sequences are active in a cell. In determining the causes of diseases, epigenetic markers are often more important than genetic ones, as the difference between two types of cells, such as a cancer cell and a normal cell, is often due to the changes in the epigenome, rather than irregularities in the DNA sequence itself.

A new study by Hopkins scientists published on Mar. 20, 2014 on the American Journal of Human Genetics website, delineates the connection between the genomic and epigenomic maps of DNA. These scientists working at the Center for Epigenetics at the Johns Hopkins University School of Medicine have developed several innovative techniques to conduct epigenetic research.

Andrew Feinberg, the director of the Center for Epigenetics; Dani Fallin, a professor and chair of the Department of Mental Health at the Bloomberg School of Public Health and a co-leader of this study; and the members of their research team first started their investigation of the overlay of genetic and epigenetic maps by analyzing the genetic data of hundreds of healthy individuals. They wanted to establish the normal or standard epigenetic pattern to which they could subsequently compare diseased patterns.

The investigators, after having determined the standard pattern, proceeded to narrow their focus on a single type of change in the epigenome. They looked at methylation, the process by which a methyl group is attached to a specific site on the DNA. While determining how methylation causes changes in protein production, the team observed that blocks of methylation patterns overlapped with blocks of DNA. These methylation blocks were, in fact, much shorter in length. This lead the researchers to conclude that genes controlling the production of proteins had to lie somewhere other than in the genetic blocks.

Prior to these findings from the Center for Epigenetics, scientists thought there were severe limitations to locating the change in the genetic material that resulted in the particular disease. Now, researchers can narrow down their searches, concluding that a few hundred nucleotides are possibly responsible for an illness by studying the effects of varying the epigenome through DNA methylation.

Researchers at the Center for Epigenetics hope to further expand their inquiry of the genetic source of diseases. They would like to extend their analysis so that methylation patterns can be associated with specific disorders and conditions.