The third solution mentioned above for solving potential allele dropout with primer binding site mutations is to add an additional PCR primer to the assay that can hybridize properly to the alternative allele when it exists in a sample. This has been the preferred solution for Applied Biosystems (e.g., Wallin et al. 2002) while Promega have moved their primers to overcome allele dropout problems (Nelson et al. 2002). According to their publications, Applied Biosystems has added an additional primer to correct for single point mutations in AmpFlSTR® primer binding sites for D16S539 (Wallin et al. 2002), VWA (Lazaruk et al. 2001), and D8S1179 (Leibelt et al. 2003).
As with any region of DNA, mutations can and do occur at STR loci. By some not completely characterized mechanism, STR alleles can change over time (Ellegren 2004). Theoretically, all of the alleles that exist today for a particular STR locus have resulted from only a few 'founder' individuals by slowly changing over tens of thousands of years (Wiegand et al. 2000). The mutational event may be in the form of a single base change or in the length of the entire repeat. The molecular mechanisms by which STRs mutate are thought to involve replication slippage or defective DNA replication repair (Nadir et al. 1996, Ellegren 2004).
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This book discusses the futility of curing stammering by common means. It traces various attempts at curing stammering in the past and how wasteful these attempt were, until he discovered a simple program to cure it. The book presents the life of Benjamin Nathaniel Bogue and his struggles with the handicap. Bogue devotes a great deal of text to explain the handicap of stammering, its effects on the body and psychology of the sufferer, and its cure.