<p>It has been one of the toughest problems in genetics. How do investigators figure out not just what genes are involved in causing a disease, but what turns those genes on or off? What makes one person with the genes get the disease and another not?<br /><br /></p>.<p>Now, in a pathbreaking paper, researchers at the Johns Hopkins University School of Medicine and the Karolinska Institute in Sweden report a way to evaluate one gene-regulation system: chemical tags that tell genes to be active or not. Their test case was of patients with rheumatoid arthritis, a crippling autoimmune disease that affects 1.5 million Americans.<br /><br />It was an investigation of epigenetics, a popular area of molecular biology that looks for modifications of genes that can help determine disease risk.<br /><br />“This is one of the first studies that looks for an epigenetic disease association in a really rigorous fashion,” said Bradley Bernstein of Harvard, who was not associated with the study. Kun Zhang of the University of California, San Diego, made a similar observation.<br /><br />In previous genomic studies, researchers with papers in leading journals “have made major claims, but after a few months or a year they were retracted,” he said. Those investigators, Zhang added, “did not treat their data very carefully.” In the new study, researchers compared 354 newly diagnosed rheumatoid arthritis patients and 337 healthy people who served as controls. The goal was to review both groups’ white blood cells, examining their DNA for chemical tags — methyl groups — that could attach themselves to genes and turn them on or off.<br /><br />It was much more complicated than just studying genes themselves. Researchers know a gene will remain stable, but the chemical tags that turn the genes on and off are not so reliable. <br /><br />Their presence can be affected by the environment or medications or even the activity of other, distant genes. They can be a consequence of a disease or set off a disease.</p>
<p>It has been one of the toughest problems in genetics. How do investigators figure out not just what genes are involved in causing a disease, but what turns those genes on or off? What makes one person with the genes get the disease and another not?<br /><br /></p>.<p>Now, in a pathbreaking paper, researchers at the Johns Hopkins University School of Medicine and the Karolinska Institute in Sweden report a way to evaluate one gene-regulation system: chemical tags that tell genes to be active or not. Their test case was of patients with rheumatoid arthritis, a crippling autoimmune disease that affects 1.5 million Americans.<br /><br />It was an investigation of epigenetics, a popular area of molecular biology that looks for modifications of genes that can help determine disease risk.<br /><br />“This is one of the first studies that looks for an epigenetic disease association in a really rigorous fashion,” said Bradley Bernstein of Harvard, who was not associated with the study. Kun Zhang of the University of California, San Diego, made a similar observation.<br /><br />In previous genomic studies, researchers with papers in leading journals “have made major claims, but after a few months or a year they were retracted,” he said. Those investigators, Zhang added, “did not treat their data very carefully.” In the new study, researchers compared 354 newly diagnosed rheumatoid arthritis patients and 337 healthy people who served as controls. The goal was to review both groups’ white blood cells, examining their DNA for chemical tags — methyl groups — that could attach themselves to genes and turn them on or off.<br /><br />It was much more complicated than just studying genes themselves. Researchers know a gene will remain stable, but the chemical tags that turn the genes on and off are not so reliable. <br /><br />Their presence can be affected by the environment or medications or even the activity of other, distant genes. They can be a consequence of a disease or set off a disease.</p>