New tool pinpoints genetic sources of disease
A new study, part-funded by the European Research Council, has shown a connection between the ‘maps’ of a genome or in-reversible chemical changes to DNA, often known as the epigenome. Many diseases have been found to have their origins in genomes and epigenomes.
“By showing the connections between genetic variants and epigenetic information, we’re providing epidemiologists with a road map,” said Dr Andrew Feinberg of Johns Hopkins University in Maryland, United States. “Epigenetic tags show how disease-causing genetic variants might affect distant genes that in turn contribute to the disease.”
Feinberg said it has long been known that individual genetic variants in sections of DNA that don’t contain blueprints for proteins (once thought of as “junk DNA”) seem to alter the quantity of proteins produced far afield. That phenomenon has made it very hard for researchers to pinpoint the source of some genetic diseases or targets for their treatment. This study, Feinberg says, shows that these genetic variants may be acting on distant protein-forming genes by influencing epigenetic tags, or chemical add-ons, atop the DNA.
The team analysed genetic data from hundreds of healthy participants in three studies to first figure out what a normal epigenetic pattern looks like. The researchers zoomed-in on one type of epigenetic change, the attachment of a chemical tag called a methyl group to a particular site on DNA. Known as methylation, these tags affect whether genes produce any protein, and if so, how much.
The team then looked for the relationship between the resulting epigenetic data and genetic data. Human genetic code is marked by blocks of DNA that children tend to inherit from their parents in unbroken chunks called haplotypes. One of these blocks is often suspected as a cause when a genetic disease arises. However, since the blocks comprise of hundreds of thousands of “letters” of DNA code, researchers are not often able to identify the mutation, or the protein-forming genes it affects, which may lie somewhere else in the block.
Epigenetic signatures like methylation patterns also occur in blocks (GeMes) for methylation blocks controlled by genes. The researchers found that the GeMes overlapped with the long genetic blocks but were much shorter. That led them to suspect that the protein-coding genes are turned on or off by those tags which must be at the root of the disease associated with a particular genetic variant found elsewhere in the block.
Yun Liu, Ph.D., a postdoctoral fellow in Feinberg’s laboratory, said: “Now, by detecting just one variation in DNA methylation, or one GeMe, a researcher will know that one or more of the few hundred methylated nucleotides are possibly causing the disease.”
The group’s next step, he says, will be to look for GeMes associated with specific diseases, such as Crohn’s and cirrhosis, in which researchers have struggled to isolate the problematic part of the genetic code.
The findings were reported on the website of the American Journal of Human Genetics.
