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Mutation detection by TaqMan-allele specific amplification: Application to molecular diagnosis of glycogen storage disease type Ia and medium-chain acyl-CoA dehydrogenase deficiency

✍ Scribed by Kunihiro Fujii; Yoichi Matsubara; Jun Akanuma; Kazutoshi Takahashi; Shigeo Kure; Yoichi Suzuki; Masue Imaizumi; Kazuie Iinuma; Osamu Sakatsume; Piero Rinaldo; Kuniaki Narisawa


Publisher
John Wiley and Sons
Year
2000
Tongue
English
Weight
271 KB
Volume
15
Category
Article
ISSN
1059-7794

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✦ Synopsis


We have devised an allele-specific amplification method with a TaqMan fluorogenic probe (TaqMan-ASA) for the detection of point mutations. Pairwise PCR amplification using two sets of allele-specific primers in the presence of a TaqMan probe was monitored in real time with a fluorescence detector. Difference in amplification efficiency between the two PCR reactions was determined by "threshold" cycles to differentiate mutant and normal alleles without post-PCR processing. The method measured the efficiency of amplification rather than the presence or absence of end-point PCR products, therefore allowing greater flexibility in designing allele-specific primers and an ample technical margin for allelic discrimination. We applied the TaqMan-ASA method to detect a prevalent 727G>T mutation in Japanese patients with glycogen storage disease type Ia and a common 985A>G mutation in Caucasian patients with medium-chain acyl-CoA dehydrogenase deficiency. The method can be automated and may be applicable to the DNA diagnosis of various genetic diseases.