Method for detecting polymorphisms in restriction fragments of two or more samples, comprising the steps of: (a) providing two or more nucleic acid samples; (b) digesting each nucleic acid sample with at least one restriction endonuclease to obtain a set of restriction fragments; (c) providing double stranded synthetic adaptors comprising - a 5' primer-compatible sequence, followed by a sample-specific identifier section, and - a 3' end that can be ligated to the blunt or protruding end of a restriction fragment; (d) ligating the double stranded synthetic adaptors to the restriction fragments in the set, to provide a set of adaptor-ligated restriction fragments; (e) optionally amplification of the set of adaptor-ligated restriction fragments, with one or more primers that at least complementary to: - the sample-specific identifier section, - a section that is complementary to the remains of the recognition sequence of the restriction endonuclease, to provide for amplified adaptor-ligated restriction fragments (amplicons); (f) determining the sequence of at least - the sample-specific identifier section; - the remains of the recognition sequence of the restriction endonuclease; and, - part of the sequence of the restriction fragment located adjacent to the remains of the recognition sequence of the restriction endonuclease; and (g) detecting polymorphisms in the sequence of the adaptor-ligated restriction fragments in the two or more samples obtained in step (f). (a) providing two or more nucleic acid samples; (b) digesting each nucleic acid sample with at least one restriction endonuclease to obtain a set of restriction fragments; (c) providing double stranded synthetic adaptors comprising - a 5' primer-compatible sequence, followed by a sample-specific identifier section, and - a 3' end that can be ligated to the blunt or protruding end of a restriction fragment; - a 5' primer-compatible sequence, followed by a sample-specific identifier section, and - a 3' end that can be ligated to the blunt or protruding end of a restriction fragment; (d) ligating the double stranded synthetic adaptors to the restriction fragments in the set, to provide a set of adaptor-ligated restriction fragments; (e) optionally amplification of the set of adaptor-ligated restriction fragments, with one or more primers that at least complementary to: - the sample-specific identifier section, - a section that is complementary to the remains of the recognition sequence of the restriction endonuclease, to provide for amplified adaptor-ligated restriction fragments (amplicons); - the sample-specific identifier section, - a section that is complementary to the remains of the recognition sequence of the restriction endonuclease, (f) determining the sequence of at least - the sample-specific identifier section; - the remains of the recognition sequence of the restriction endonuclease; and, - part of the sequence of the restriction fragment located adjacent to the remains of the recognition sequence of the restriction endonuclease; and - the sample-specific identifier section; - the remains of the recognition sequence of the restriction endonuclease; and, - part of the sequence of the restriction fragment located adjacent to the remains of the recognition sequence of the restriction endonuclease; and (g) detecting polymorphisms in the sequence of the adaptor-ligated restriction fragments in the two or more samples obtained in step (f).