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Antisense RNA Causes Genetic Disease

 
  May, 5 2003 9:48
your information resource in human molecular genetics
 
     
Most human genetic diseases are caused by a mutation within a particular gene that affects how much of a protein it makes or how the protein functions. In a new study to be published in Nature Genetics, scientists have uncovered a new mechanism for genetic diseases that involves antisense RNA--an unusual form of RNA that blocks the expression of genes.

Professor D.R. Higgs and colleagues at the Weatherall Institute of Molecular Medicine in Oxford, UK, studied the mechanism of disease in a patient with an inherited form of anemia called alpha thalassemia. This disease is caused by mutations in the alpha globin gene; however, in this case the patient's gene looked perfectly normal. The researchers found that the patient's DNA was rearranged so that a portion of another, unrelated gene, called LUC7L, had moved right next to the alpha globin gene. This rearrangement shut off the alpha globin gene by producing antisense RNA.

Messenger RNA is referred to as "sense" RNA because it is read by the cell to make a gene product or protein. An RNA strand whose sequence is complementary to the messenger RNA is called "antisense". Typically cells do not make antisense RNA. But in the thalassemia patient, when the LUC7L gene moved to the end of the alpha globin gene it drove expression of the gene in the antisense direction. The antisense RNA then blocked expression of the normal gene. The same process might be involved in other inherited diseases.

Author contact:
Professor D.R. Higgs
MRC Molecular Hematology Unit
Weatherall Institute for Molecular Medicine
John Radcliffe Hospital
Headington, Oxford
UK
Tel: +44 1865 222293
E-mail drhiggs@molbiol.ox.ac.uk

(C) Nature press release.


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