FISH Beats Molecular Karyotyping

We would like to comment on John Ashkenas' recent article on molecular karyotyping in the Jan. 17, 2005, issue of The Scientist.¹ We attended the American Society of Human Genetics meeting as well and came away with a different impression of molecular karyotyping. While this technique will eventually and undoubtedly reveal new insights into human genome structure and copy-number variation, the data are still quite noisy and often unconvincing. Indeed, this copy-number variation is probably the source of much of the noise, as well as variability in the quality of C₀ t1 DNA used to quench repetitive sequence hybridization.²These factors contribute to difficulties in unequivocal interpretation of array comparative genomic hybridization results.

Conventional FISH [fluorescence in situ hybridization], on the other hand, provides a context-dependent measurement of copy number that can unequivocally identify balanced chromosome rearrangements (this is a challenge for molecular karyotyping, especially for detection of balanced intrachromosomal rearrangements). ...