There is disclosed a method for examining polymorphisms in a nucleotide sequence of a first sample of nucleic acid comprising the steps of: (a) forming a population of nucleic acid fragments bearing the said nucleotide sequence: (b) combining the population of nucleic acid fragments with a population of a synthetic nucleotide construct which construct is capable of forming duplexes with the nucleic acid fragments but which contains one or more deliberate nucleotide substitution(s) and/or deletion(s) and/or insertions(s) which is/are (i) opposite to a known variable nucleotide or sequence of nucleotides within the sequence under examination and/or (ii) contiguous with a nucleotide which is opposite to a known variable nucleotide or sequence of nucleotides within the sequence under examination: (c) permitting duplex formation within the combined populations; and (d) separating the duplexes formed in step (c). <IMAGE>
