Patent ID: 8785353

Claim:
A method for identifying one or more polymorphisms, comprising the steps of: (a) providing a first nucleic acid sample of interest; (b) performing a complexity reduction on the first nucleic acid sample to provide a first library of the first nucleic acid sample, which comprises: (i) digesting the nucleic acid sample with at least one restriction endonuclease to fragment it into restriction fragments; (ii) ligating the restriction fragments obtained with at least one double-stranded synthetic oligonucleotide adaptor having one end compatible with one or both ends of the restriction fragments to produce adapter-ligated restriction fragments (ALRFs); (iii) contacting said ALRFs with one or more oligonucleotide primers under hybridizing conditions; and (iv) amplifying said ALRFs by elongation of the one or more oligonucleotide primers, wherein at least one of the one or more oligonucleotide primers includes a nucleotide sequence having the same nucleotide sequence as the terminal parts of the strands at the ends of said ALRFs, including the nucleotides involved in the formation of the target sequence for said restriction endonuclease and including at least part of the nucleotides present in the adaptors, and wherein the adaptor and/or the primer comprises a tag, and wherein, optionally, at least one of said primers includes at its 3′ end a selected sequence comprising at least one nucleotide located immediately adjacent to the nucleotides involved in the formation of the target sequence for said restriction endonuclease; (c) consecutively or simultaneously performing steps (a) and (b) with a second or further nucleic acid sample of interest to obtain a second or further library of the second or further nucleic acid sample; (d) sequencing at least a portion of the first library and the second or further library; (e) aligning the sequences obtained in step (d) to obtain an alignment; and (f) determining one or more polymorphisms between the first nucleic acid sample and second or further nucleic acid sample in the alignment of step (e).