Human biology is a mysterious thing, which is why perplexing diseases like high blood pressure, diabetes and psychiatric disorders are so hard to predict and, as is often the case, to treat as well. Another complexity involves understanding how and why one individual might contract a debilitating or deadly disease like depression or cancer, while an identical twin remains the epitome of health.
Now, though, scientists have identified a clue that could eventually help them figure out such riddles. They know that the human genome is filled with at least four million gene switches that inhabit bits of DNA which were at one time written off as “junk” but have turned out to play crucial roles in controlling how cells, organs and other tissues behave,The New York Times reported.
“The discovery, considered a major medical and scientific breakthrough, has enormous implications for human health because many complex diseases appear to be caused by tiny changes in hundreds of gene switches,” said the paper.
Junk in DNA contains a ‘complex system’
The findings, which are the result of a large federal project that involves 440 scientists from 32 labs around the world, will have an immediate impact on the understanding of how alterations in the non-gene portions of DNA actually contribute to the formation of human diseases. That in turn could lead to the development of new drugs aimed at treating those diseases. The discovery can also help explain how the environment affects risk, the paper said.
In the case of twins, researchers note, just small changes in environmental exposure can alter gene switches slightly, resulting in one twin getting a disease while the other does not.
As scientists dug deeper into the “junk” – described as parts of the DNA that are not actual genes that contain instructions for proteins – they found a complex system that controls genes in which at least 80 percent of the DNA is both active and needed. In all, the system of switches act much like dimmer switches for lights in that they control which genes are used in a cell and when they are used, in addition to determining whether a cell becomes a neuron or a liver cell.
“It’s Google Maps,” Eric Lander, president of the Broad Institute, a joint research endeavor of Harvard and the Massachusetts Institute of Technology, told the Times.
By comparison, the project’s predecessor, the Human Genome Project, which govern the entire sequence of human DNA, “was like getting a picture of Earth from space,” said Lander.
“It doesn’t tell you where the roads are, it doesn’t tell you what traffic is like at what time of the day, it doesn’t tell you where the good restaurants are, or the hospitals or the cities or the rivers,” he added, according to the Times.
The new result “is a stunning resource,” said Lander, who was not involved in the latest project but was a leader in the Human Genome Project. “My head explodes at the amount of data.”
Researchers published their discoveries recently in a half-dozen papers in the journal Nature, as well in 24 papers in Genome Research and Genome Biology. Additionally, the Journal of Biological Chemistry is publishing six review articles, while Science has agreed to publish yet another article related to the findings, the Times said.
‘A really big deal’
Human DNA is “a lot more active than we expected, and there are a lot more things happening than we expected,” Ewan Birney of the European Molecular Biology Laboratory-European Bioinformatics Institute, a lead researcher on the project, told the paper in an interview.
In one of the papers for Nature, scientists tie the gene switches to a host of human diseases including multiple sclerosis, rheumatoid arthritis, lupus, celiac disease, Crohn’s disease – and to other physical traits such as height.
In large studies over the past 10 years, researchers have discovered that small changes in human DNA sequences boost the risk of a person contracting those diseases. But such changes were in the junk, now often called the dark matter – they were not gene changes – and the significance of them was not clear. The new data shows that many of those changes alter gene switches and are in turn very significant.
“Most of the changes that affect disease don’t lie in the genes themselves; they lie in the switches,” said Michael Snyder, a Stanford University researcher for the project, dubbed Encode, for Encyclopedia of DNA Elements.
That, adds Dr. Bradley Bernstein, an Encode researcher at Massachusetts General Hospital, “is a really big deal.”
“I don’t think anyone predicted that would be the case,” Bernstein added.