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Blindness Linked To The Cytoskeleton?

of those are caused by mutations in genes residing on the X chromosome. Approximately one fifth of the X-chromosomal cases is caused by mutations within the gene identified by Uwe Schwahn and colleagues from the Max Planck Institute for Molecular Genetics in Berlin (Dahlem). X-linked RP is considered one of the most severe forms in terms of onset and progression. The disease onset occurs by the time the patient has turned 20 and progresses to legal blindness within 10-20 years.

The novel gene was identified by a molecular-biology strategy known as ‘positional cloning approach’. The isolation of genes by positional cloning is based on the location of the gene in the human genome, without detailed information on the biological function of the gene product.

The challenge was to find the needle of 3,800 base pairs (which represents the protein coding portion of the RP2 gene) in a haystack of 4,000,000 base pairs of X-chromosomal DNA where, according to data from family studies, the RP2 gene must be located. In order to get a hint where to look first, the researchers applied the relatively new yeast artificial chromosome (YAC) representation hybridization technique. The first report on this technique was issued only two years ago when they and their co-workers at the University Hospital Nijmegen (The Netherlands) had narrowed down the RP3 gene region and finally cloned the gene. The technique essentially compares the DNA of a control to that of patients. If there is a difference between them, this shows up as aberrant pattern in the patients DNA.

The research group led by Wolfgang Berger identified such an aberrant pattern in one out of 26 patients. The aberrant hybridization pattern turned out to be caused by an insertion of a mobile DNA element, called LINE1 (Long Intersper
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Contact: Wolfgang Berger
berger@mpimg-berlin-dahlem.mpg.de
49-30-8413-1253
Max-Planck-Gesellschaft
4-Aug-1998


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