Boston, Mass. -- A subtle mutation affecting the epigenome - a set of dynamic factors that influence gene activity -- may lead to an inherited form of mental retardation that affects boys, find researchers at Children's Hospital Boston. The disorder, which also involves cleft lip or cleft palate, appears to hinge on an enzyme working in a biological pathway that may offer several potential drug targets.
The study, published online July 11 in the journal Nature, reveals that this enzyme is a histone demethylase and works with a key genetic partner to help keep neuronal cells alive during development of the embryonic brain. Patients with this form of mental retardation are known to have mutations in the gene that encodes the active part of this enzyme. The findings may help scientists further understand the underlying biological reasons why X-linked disorders cause cognitive impairment and develop new therapies to treat or prevent them.
"Human genetics has made great strides in identifying genes as potential causes of diseases and disorders, but we don't know much about how they work," says senior author Yang Shi, PhD, the Merton Bernfield Professor of Neonatology in the Newborn Medicine division at Children's. "We knew this was a biologically relevant gene. We wanted to understand the etiology, so we asked why the gene causes problems when it is mutated. Here, we have identified a direct target in neuronal and craniofacial development."
The fast-moving young field known as epigenetics is revealing the dynamic structures and processes that organize, index and control access to the information stored in the DNA code. The epigenetic program orchestrates different combinations of gene activity allowing cells with identical genomes to be transformed into more than 200 different specialized tissues and organs in our bodies.
When most people think of DNA, they picture the iconic spiraling ladder of naked DNA. But in nature,
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Children's Hospital Boston