Detection of low-level somatic DNA mutations and minority alleles within a wild-type sample is crucial in fields of medicine,such as cancer,prenatal diagnosis and infectious diseases.Increasing enrichment methods have been developed to study this challenging area.They are typically segregate by their ability to enrich for,and detect,either known or unknown mutations,including COLD-PCR,ice-COLD-PCR,TT-PCR,PNA-mediated PCR,WTB-PCR and digital PCR.In this review,we discuss theoretical principles and relative advantages and disadvantages of these techniques,and put an emphasis on their applications in fields of diseases.