New DNA-analysis techniques (minireview)

The increasing knowledge about specific human genes and their alterations causing genetic diseases, requires new strategies and methods for mutation-detection. However, the large molecular heterogeneity of such mutations in each gene sets serious limitations to this approach. The polymerase chain reaction has become the basis of several new developments aiming to overcome this problem. Recently developed methods to search for unknown mutations are the denaturing gradient electrophoresis, chemical mismatch cleavage, single stranded conformation polymorphisms and direct genomic sequencing. Known mutations in a particular gene can be detected by the allele specific hybridization, the amplification refractory mutation system, the competitive oligonucleotide priming reaction or the oligonucleotide ligation assay. As spin-off of the human genome sequencing projects, automated DNA-sequencing may in the future become the easiest, fastest, most reliable and most informative technique and a powerful day-to-day method in every genetics and clinical chemistry laboratory.