A combinatorial approach for fast, high-resolution mapping.
High-resolution physical maps can be used as a scaffold for several subsequent studies, such as sequencing projects and positional cloning of disease genes and genetic elements that regulate gene expression. Here we describe a method for fast, high-resolution physical mapping on stretched DNA molecules, based on a combinatorial multi-FISH approach. Fluorescent labels are assigned to a binary code and probes are identified by a binary tag according to their labeling. To validate the approach, we have mapped eight probes covering a region of about 300 kb on human chromosome 11 with three hybridization assays. This approach enables one to determine the structural organization of a large region by means of the order of its clones, without ambiguities. The structure established in a control cell constitutes a reference for further studies, to detect rearrangements displayed by disease cells and to find differences shown by different cell types and organisms.
Conti
Chiara
C
Laboratoire de Stabilité des Génomes, Département de Structure et Dynamique des Génomes, Institut Pasteur, 25, rue du Dr. Roux, Paris Cedex, France.
Bensimon
Aaron
A
D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015335:Molecular Probes / Q000235:genetics*; D020161:Physical Chromosome Mapping / Q000379:methods*
D015335:Molecular Probes