Ligation overcomes terminal underrepresentation in multiple displacement amplification of linear DNA.

Several methods have been developed to achieve a whole genome amplification (WGA). Particularly promising is a variant, called multiple displacement amplification (MDA), which exploits the high processivity of ¦29 phage DNA polymerase. Even though MDA has been successfully used for many applications, some problems have been reported. For example, sequences near the ends of linear chromosomes appear underrepresented after MDA. We demonstrated that the ligation of templates helps to overcome under-representation of the termini and expands the potential for the application of MDA. It is useful to obtain faithful amplifications of small, linear templates that otherwise could not be successfully amplified.