Virtual genome scan: A tool for restriction landmark-based scanning of thehuman genome

There is substantial interest in implementing technologies that allow compa risons of whole genomes of individuals and of tissues and cell populations. Restriction landmark genome scanning (RLGS) is a highly resolving gel-base d technique in which several thousand fragments in genomic digests are Visu alized simultaneously and quantitatively analyzed. The widespread use of RL GS has been hampered by difficulty in deriving sequence information for dis played fragments and a lack of whole-genome sequence-based framework for in terpreting RLGS patterns. We have developed informatics tools for compariso ns of sample derived RLGS patterns with patterns predicted from the human g enome sequence and displayed as Virtual Genome Scans (VGS). The tools devel oped allow sequence prediction of fragments in RLGS patterns obtained with different restriction enzyme combinations. The utility of VGS is demonstrat ed by the identification of restriction fragment length polymorphisms, and of amplifications, deletions, and methylation changes in tumor-derived CpG islands and the characterization of an amplified region in a breast tumor t hat spanned < 230 kb on 17q23.