Detection of triplet repeat expansion in the human genome by use of hybridization signal intensity

Triplet repeat disease is a group of hereditary neurodegenerative disorders caused by expansion of trinucleotide repeats such as CAG/CTG, CGG/CCG, and GAA/TTC. Direct detection of the expansion in the patient's genome shortcu ts the tedious process needed for identification of disease genes by conven tional approaches. Here we describe a method to detect triplet repeat expan sion from the hybridization signal intensity, Using a digoxigenin-labeled ( CTG)9 probe, the hybridization intensity and number of repeats showed a goo d linear correlation. The technique detected expansion in genomic DNA in al l cases with moderate or large expansion. Even in the case of a small expan sion, this method could detect the mutant fragment. The technique has advan tages over related techniques because it is more sensitive and can be appli ed to cases where a small repeat expansion is involved. (C) 2000 Academic P ress.