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New insights into progressive hearing loss
Date:4/12/2009

author on the human study, from Hospital Ramn y Cajal and Centro de Investigacin Biomdica en Red de Enfermedades Raras, Madrid, Spain.

MicroRNAs are tiny snippets of genetic information that, it is increasingly clear, can have dramatic consequences. Only five years ago, their role in human biology and disease was unknown. Today, it is becoming clear that these little molecules can control the activity of many genes. MicroRNAs can bind to the messengers involved in protein production in cells, disrupting this process.

"No one has seen a disease-causing mutation in the mature sequence of a microRNA," says Dr Moreno-Pelayo. "This is the first microRNA gene associated with hearing impairment and, remarkably, it is the first to be associated with an inherited disorder."

In the mouse, the precise role of the mutation can be examined. Mutation of the miR-96 gene seemed to disrupt development of intricate sensory hair cells in the mutant mice. Mice with two copies of the mutant gene had malformed hair cells from birth and the cells degenerated from an early age. In mice with one copy of the mutant gene, the effects were less severe, but became worse with age.

"The mutation - a change of a single letter of genetic code from A to T - in this tiny stretch of sequence is enough to lead to dramatic loss of hearing in these mice," explains Dr Morag Lewis, a Sanger Institute scientist, who found this mutation. "We wondered if this single change was preventing the miR-96 from binding to the sites it would normally target to influence gene activity, and looked at ways to determine if this was the case."

The scientists looked at many thousands of messengers to determine which of them seemed altered in the mice with the miR-96 mutation. Significantly, a handful of these seemed to play vital roles in the working of the ear.

"Finding that these targets are affected by the mutation in miR-96 was a real landmark in our studies," say
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Contact: Don Powell
don@sanger.ac.uk
44-077-537-75397
Wellcome Trust Sanger Institute
Source:Eurekalert

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