Pinpointing Genetic Causes of Diseases
Researchers from North Carolina State University, UNC-Chapel Hill, and other institutions have taken the first steps toward creating a roadmap that may help scientists narrow down the genetic cause of numerous diseases. Their work also sheds new light on how heredity and environment can affect gene expression. The study was published online April 13th 2014 in Nature Genetics.
A release from North Carolina State explains that pinpointing the genetic causes of common diseases is not easy because multiple genes may be involved with a disease. Not only that, but disease-causing variants in DNA often do not act directly. Instead, they activate nearby genes. To add to the complexity, genetic activation is not like a simple on/off switch on a light. It behaves more like a "dimmer switch". Some people may have a particular gene turned all the way up, while others have it only turned halfway on, completely off, or somewhere in between. And different factors, such as DNA or the environment, play a role in the dimmer switch's setting.
The release quotes Fred Wright, NC State professor of statistics and biological sciences, director of NC State's Bioinformatics Center and co-first author of the study, as saying, "Everyone has the same set of genes. It's difficult to determine which genes are heritable, or controlled by your DNA, versus those that may be affected by the environment. Teasing out the difference between heredity and environment is key to narrowing the field when you're looking for a genetic relationship to a particular disease."
Wright, with co-first author Patrick Sullivan, Distinguished Professor of Genetics and Psychiatry at UNC-Chapel Hill and director of the Center for Psychiatric Genomics, and national and international colleagues, analyzed blood sample data from 2,752 adult twins (both identical and fraternal) from the Netherlands Twin Register and an additional 1,895 participants from the Netherlands Study of Depression and Anxiety. For all 20,000 individual genes, they determined whether those genes were heritable – controlled by the DNA "dimmer switch" – or largely affected by environment.
"Identical twins have identical DNA," Wright explains, "so if a gene is heritable, its expression will be more similar in identical twins than in fraternal twins. This process allowed us to create a database of heritable genes, which we could then compare with genes that have been implicated in disease risk. We saw that heritable genes are more likely to be associated with disease – something that can help other researchers determine which genes to focus on in future studies."