Measurement of locus copy number by hybridisation with amplifiable probes

Despite its fundamental importance in genome analysis, it is only recently that systematic approaches have been developed to assess copy number at spe cific genetic loci, or to examine genomic DNA for submicroscopic deletions of unknown location. In this report we show that short probes can be recove red and amplified quantitatively following hybridisation to genomic DNA, Th is simple observation forms the basis of a new approach to determining locu s copy number in complex genomes, The power and specificity of multiplex am plifiable probe hybridisation is demonstrated by the simultaneous assessmen t of copy number at a set of 40 human loci, including detection of deletion s causing Duchenne muscular dystrophy and Prader-Willi/Angelman syndromes, Assembly of other probe sets will allow novel, technically simple approache s to a wide variety of genetic analyses, including the potential for extens ion to high resolution genome-wide screens for deletions and amplifications .