Abstract: Methods for estimating the size of disease-associated polynucleotide repeat expansions in genes are disclosed which use restriction enzymes that do not cut within a repeat expansion and which are frequent cutting restriction enzymes that cut genomic DNA outside of the expansion into fragments of a size below the threshold capable of detection. A hybridisation probe that can bind to multiple sites within the expansion is then used to estimate its length and to correlate that to the diagnosis or prognosis of disease.