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Direct detection of novel expanded trinucleotide repeats in the human genome


Expansion of trinucleotide repeats can give rise to genetic disease. We have developed a technique, repeat expansion detection (RED), that can identify potentially pathological repeat expansion without prior knowledge of chromosomal location. Human genomic DNA is used as a template for a two–step cycling process that generates oligonucleotide multimers when expanded trinucleotide sequences are present at the level found in myotonic dystrophy and fragile–X patients. We have identified at least one new locus exhibiting trinucleotide expansion. Analysis of three families transmitting a long CTG repeat shows that the allele in these families corresponds to a locus on chromosome 18. RED constitutes a powerful tool to identify other diseases caused by this mechanism, particularly diseases associated with anticipation.

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Schalling, M., Hudson, T., Buetow, K. et al. Direct detection of novel expanded trinucleotide repeats in the human genome. Nat Genet 4, 135–139 (1993).

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