DYNAMIC MOLECULAR COMBING - STRETCHING THE WHOLE HUMAN GENOME FOR HIGH-RESOLUTION STUDIES

DNA in amounts representative of hundreds of eukaryotic genomes was ex tended on silanized surfaces by dynamic molecular combing. The precise measurement of hybridized DNA probes was achieved directly without re quiring normalization. This approach was validated with the high-resol ution mapping of cosmid contigs on a yeast artificial chromosome (YAC) within yeast genomic DNA. It was extended to human genomic DNA for pr ecise measurements ranging from T to 150 kilobases, of gaps within a c ontig, and of microdeletions in the tuberous sclerosis 2 gene on patie nts' DNA. The simplicity, reproducibility, and precision of this appro ach makes it a powerful tool for a variety of genomic studies.