OBJECTIVES: The UGT1A1 promoter contains a (TA)n repeat polymorphism. The 7 repeat allele is associated with decreased enzyme activity and patients homozygous for this allele treated with irinotecan may experience life-threatening toxicity. Here, we have compared three methods [DNA sequencing, fragment analysis, and the Invader assay (Third Wave Technologies)] for genotyping this polymorphism. RESULTS: All of the DNA samples (n=119) had concordant genotype calls between the sequencing and size-based methods. The Invader method was also concordant if the genotypes were 6/6, 6/7, or 7/7. Both the size-based method and the Invader method had straightforward data analysis, while interpretation of the sequencing results was occasionally more challenging. The Invader method required more concentrated DNA for analysis, was more expensive, and had a limited genotyping spectrum. CONCLUSION: All three methods were valuable for genotyping the UGT1A1 (TA)n repeat, with the sequencing and size-based assays having the fewest drawbacks.
OBJECTIVES: The UGT1A1 promoter contains a (TA)n repeat polymorphism. The 7 repeat allele is associated with decreased enzyme activity and patients homozygous for this allele treated with irinotecan may experience life-threatening toxicity. Here, we have compared three methods [DNA sequencing, fragment analysis, and the Invader assay (Third Wave Technologies)] for genotyping this polymorphism. RESULTS: All of the DNA samples (n=119) had concordant genotype calls between the sequencing and size-based methods. The Invader method was also concordant if the genotypes were 6/6, 6/7, or 7/7. Both the size-based method and the Invader method had straightforward data analysis, while interpretation of the sequencing results was occasionally more challenging. The Invader method required more concentrated DNA for analysis, was more expensive, and had a limited genotyping spectrum. CONCLUSION: All three methods were valuable for genotyping the UGT1A1 (TA)n repeat, with the sequencing and size-based assays having the fewest drawbacks.
Authors: Daniel H Johnson; Charles Venuto; Marylyn D Ritchie; Gene D Morse; Eric S Daar; Paul J McLaren; David W Haas Journal: Pharmacogenet Genomics Date: 2014-04 Impact factor: 2.089
Authors: Tristan M Sissung; Roberto H Barbier; Douglas K Price; Teri M Plona; Kristen M Pike; Stephanie D Mellott; Ryan N Baugher; Gordon R Whiteley; Daniel R Soppet; David Venzon; Arlene Berman; Arun Rajan; Giuseppe Giaccone; Paul Meltzer; William D Figg Journal: Int J Mol Sci Date: 2020-01-30 Impact factor: 5.923
Authors: Paul J McLaren; Jean Louis Raisaro; Manel Aouri; Margalida Rotger; Erman Ayday; István Bartha; Maria B Delgado; Yannick Vallet; Huldrych F Günthard; Matthias Cavassini; Hansjakob Furrer; Thanh Doco-Lecompte; Catia Marzolini; Patrick Schmid; Caroline Di Benedetto; Laurent A Decosterd; Jacques Fellay; Jean-Pierre Hubaux; Amalio Telenti Journal: Genet Med Date: 2016-01-14 Impact factor: 8.822