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

s Karen Steel. "Any one of the strongest candidates could have explained the hearing loss effects on its own. It was a really remarkable result.

"We had gone from one amazing result - that this variant microRNA was causing these dramatic effects - to another - that miR-96 does affect genes important for normal hearing and a clear path was laid."

In the human studies, two families showed mutations in miR-96 - but they each carried the mutation at different locations in the miR-96 gene. Intriguingly, neither mutation in humans is the same letter as in the mouse, but all three are close to one another in the miR-96 sequence.

"The mutation in the second family is just one letter away from the mutation in the first and just one away from the mutation in the mouse gene. All three sit in a vital region of seven letters in the mature sequence of miR96" says Dr Angeles Menca, the Spanish team member who found the human mutations.

Remarkably, then, cases of deafness in two different organisms are both tied to equivalent microRNAs and to the equivalent region within the microRNA - just seven letters that are known to be important for interacting with the messenger targets.

"The human variants of miR-96 identified in the affected families were found to alter activity of other genes in experiments in test tubes," explains Dr Moreno-Pelayo.

The team also looked to see whether the mutations altered the production or stability of miR-96 and to see whether they affected the normal workings of miR-96. Both the genesis and function of miR-96 were impaired by these human mutations in the lab studies.

Researchers are using models of hearing in the mouse to understand human hearing deficits: by the age of ten, one in 500 children has suffered significant hearing impairment and the majority of over-70s are affected. The same genes have often been shown to be involved in deafness in both the mouse and humans.

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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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