High throughput mutation screening by automated capillary electrophoresis

Molecular diagnosis of complex inherited disorders, population screening of genetic diseases, studies of the genetic basis of variable drug response ( pharmacogenetics) as well as discovery and investigation of new drug target s (pharmacogenomics) involve screening for mutations in multiple DNA sample s. Furthermore, the development of a third generation of the human genome m ap, based on single nucleotide polymorphisms (SNPs), requires screening for allelic variants through all of the three billion basepairs in the human g enome. Thus, the need for high throughput mutation screening methods is gre at and is rapidly increasing. Traditional methods for mutation screening of ten involve slab-gel electrophoresis analyses which are laborious and diffi cult to automate. However, recent developments in capillary electrophoresis systems for DNA fragment analysis have made fully automated mutation scree ning possible and have dramatically increased the possible sample throughpu t. This review describes the recent advances in capillary electrophoresis o f DNA and summarize the various methods for mutation screening based on thi s technique.