Transposon mediated differential hybridisation, or TMDH, is a technique used to identify restriction sites. After electroporating bacteria, and transforming it with a transposon and tnpA, a mutant library is created. On extracting the genomic DNA and restriction digest, RNA run-off sequences can be created using primers for SP6 and T7 promoters. Using fluorescently labelled dNTPs, allowing the identification of the direction these sequences start from. Microarray is then used to identify the location of restriction sites.
TMDH can be used to identify genes essential for cell survival. As the transposon used will only interrupt a single gene in a cell, it is possible to identify genes essential for survival. This allows the attenuation of virulence factors of a bacterial pathogen, which when combined with animal testing, can allow the identification of vaccine candidates.
This technique is not widely used now, as restriction sites are able to be identified computationally by analysing DNA sequencing data.