Leap forward in disease diagnosis

A massive sequencing mission, 370 times larger than the Human Genome Project (HGP), has produced the first atlas of epigenetic markers in the human body. A new paper in the journal Genome Biology reveals that the atlas will act as a treasure map, guiding researchers to understand the epigenetic causes of disease from cancer to Alzheimer’s disease.

In 2003, the HGP completed the first map of all the genes in the human genome. Since then, it has become clear that genes are only part of the picture when it comes to predicting the onset, development and severity of disease. As a result, many researchers have turned to the field of epigenetics for a more complete understanding.

This is the study of the regulation of genetic activity by various molecular mechanisms, the most common and stable of which is methylation.

Methylation is the process by which “methyl groups” – molecules derived from methane, containing one carbon atom bonded to three hydrogen atoms – in the environment attach to DNA and affect gene function by turning them on or off.

A complicating factor, and one of the reasons that progress in the field has not been quite as pronounced as some had hoped, is that epigenetic markers are different in different types of cells in the human body. Whereas one can take a DNA sample from anywhere and get a picture of the overall genome, the same can’t be said for epigenetic components.

However, senior author Robert Waterland of the US Department of Agriculture Children’s Nutrition Research Centre and the Department of Molecular and Human Genetics, both at the Baylor College of Medicine in Houston, Texas, together with an international team of researchers, may have found a way around this. 

Waterland and colleagues have discovered 10,000 genomic regions in which epigenetic methylation varies between different individuals but remains consistent across the different types of tissues in a single human body. These regions are known as “correlated regions of systemic interindividual variation” (CoRSIVs) and make up about 0.1% of the genome. Their discovery paves the way for researchers to understand an individual’s epigenetic make-up, and thus disease risk in multiple cell types, through a simple biopsy.

To find these regions, the researchers traced anatomical features back to their origins. Human embryos in about the third week of development differentiate into three germ layers: the endoderm, mesoderm and ectoderm. These transform into, among other things, the thyroid, heart and brain respectively, so the team profiled DNA methylation in these tissue types, discovering a vast array of CoRSIVs.

“Because epigenetic marking has the power to stably silence or stably activate genes, any disease that has a genetic basis could equally likely have an epigenetic basis,” Waterland explains.

“There is incredible potential for us to understand disease processes from an epigenetic perspective. CoRSIVs are the entryway to that.”

This is because they allow, for the first time, epigenetic comparison of different individuals.

While the scientists may have mapped what seems like a tiny fraction of the genome, the implications are big. “

This atlas of human CoRSIVs,” they write, “provides a resource for future population-based investigations into how interindividual epigenetic variation modulates risk of disease,” and may well transform understanding of the causes of illness in the human body.

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