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        Repeat Expansion Detection (RED) and the RED Cloning Strategy

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        Trinucleotide repeat sequences are present at approx 30,000-40,000 loci in the human genome (1 ). The majority of these repeats are below 35 copies and are stably transmitted. However, unstable trinucleotide repeat expansions at some loci have been found to be the causal mutation for nearly 20 genetic neurodegenerative disorders in human (2 4 ). Most of these disorders occur at repeat lengths above 35 copies, with a tendency towards further expansion upon successive transmissions. An inverse correlation between the repeat length and disease severity/earlier age of onset, known as anticipation, has been observed in most of the families transmitting such types of diseases, suggesting that the length change of the repeats may play a role in the manifestation of anticipation. Only three motifs, CAG/CTG, CGG/CCG, and GAA/TTC, of the 10 possible trinucleotide repeat permutations have so far been associated with human disease. It remains possible that other disease phenotypes are caused by expansions of any repeat motif at any repeat containing locus. We have established a repeat detection and gene-isolation system, which allows identification of a repeat-containing gene within a couple of months.
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