THE REPEAT EXPANSION DETECTION METHOD IN THE ANALYSIS OF DISEASES WITH CAG CTG REPEAT EXPANSION - USEFULNESS AND LIMITATIONS/

The repeat expansion detection (RED) method was described to detect ex pansions of trinucleotide repeats of unknown chromosomal location. We have improved the RED method by the use of 8-mer oligonucleotides and assessed its usefulness in 30 samples from patients with spinocerebell ar ataxia type 1 (SCA1), Huntington's disease (HD), and Machado Joseph 's disease (MJD), for which the number of CAG/CTG repeats was determin ed by sequencing. There was a good correlation between the number of r epeats detected by sequencing and those identified by RED. However, in 17% of samples, the RED gave additional fragments for ligation produc ts of different size than the CAG/CTG repeat expansion detected in the sample by sequencing. The same was observed in a group of control sub jects (n = 78) without known clinical abnormalities in which products of more than 40 repeats were detected in 27% of them, indicating that CAG/CTG repeat expansions are common in the general population. Wether this corresponds to unidentified loci with expansions deserves furthe r investigation. (C) 1997 Wiley-Liss, Inc.