There are two broad groups of methods for identifying DNA sequence variations: screening (or scanning) methods and diagnostic methods. From a technical point of view, sequence variations may or may not be known to exist in a stretch of DNA in a given sample before the search is begun. Screening methods are used to search unknown sequence variations; for example, a sample from a patient with a certain genetic disease is screened for diseasecausing mutations in the different exons of a putative disease gene.
Diagnostic methods are used to determine the genetic make-up (or genotype) of a sample for a known sequence variation at a known location; for instance, a pregnant woman is genotyped for her Rh(D) status at the RHD locus. Single strand conformation polymorphism (SSCP) analysis of DNA fragments amplified by polymerase chain reaction (PCR) can be used as a screening method, a diagnostic method or both in any single electrophoretic run, depending on the purpose of the experiments and the region of DNA sequences being examined.
On the basis of the size of the DNA sequences involved, sequence variations can be of small or large scale. Small-scale sequence variations involve a few basepairs (bp), such as base substitutions and small insertions/deletions. Large-scale sequence variations involve a large stretch of DNA sequences, and are exemplified by large insertions/deletions and gross gene arrangements.
There are no definitive cut-offs between small-scale and large-scale sequence variations. However, small-scale and large-scale sequence variations, either known or unknown, do require different methods for detection.