Disclosed are new methods comprising the use of in situ hybridization to
detect abnormal nucleic acid sequence copy numbers in one or more genomes
wherein repetitive sequences that bind to multiple loci in a reference
chromosome spread are either substantially removed and/or their
hybridization signals suppressed. The invention termed Comparative Genomic
Hybridization (CGH) provides for methods of determining the relative
number of copies of nucleic acid sequences in one or more subject genomes
or portions thereof (for example, a tumor cell) as a function of the
location of those sequences in a reference genome (for example, a normal
human genome). The intensity(ies) of the signals from each labeled subject
nucleic acid and/or the differences in the ratios between different
signals from the labeled subject nucleic acid sequences are compared to
determine the relative copy numbers of the nucleic acid sequences in the
one or more subject genomes as a function of position along the reference
chromosome spread. Amplifications, duplications and/or deletions in the
subject genome(s) can be detected. Also provided is a method of
determining the absolute copy numbers of substantially all RNA or DNA
sequences in subject cell(s) or cell population(s).