Screening for genetic mutations. A review

A point mutation of a nucleotide within a single gene can have a profound e ffect on a specific organ and/or the entire human body. DNA sequences assoc iated with human diseases may differ from the corresponding normal sequence s by single nucleotide mutations or by large alterations such as deletions, insertions, duplications, or translocations of DNA segments or entire chro mosomes. As a result of the heterogeneity of DNA alterations and genetic mu tations, various screening approaches are required to detect these alterati ons. However, methods which facilitate the detection of large alterations i n the genome are typically insensitive to point mutations, whereas methods which detect point mutations are not appropriate to detect large alteration s within the genome. Since there is no single perfect method to screen for unknown mutations, combinations of these methods may be necessary for accur ate genetic diagnosis. The applications of polymerase chain reaction (PCR) technology to genomic screening have made rapid and accurate genetical diag nosis possible. Furthermore, recent developments in the technology of DNA m icroarrays have opened the way for high throughput sequence analysis by hyb ridization, which shows great potential in both molecular biology and medic ine in the near future.