Method for characterizing nucleic acid molecules

C - Chemistry – Metallurgy – 12 – Q

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C12Q 1/68 (2006.01)

Patent

CA 2233079

A method of characterizing a nucleic acid molecule is disclosed. The method comprises synthesizing DNA in the presence of a reaction mixture comprising a nucleic acid template, a primer molecule, an enzyme that extends the primer so that a DNA molecule may be synthesized, four canonical deoxynucleoside triphosphates and at least one non-canonical deoxynucleoside triphosphate. The non-canonical deoxynucleoside triphosphate is incorporated into the synthesized DNA in place of a portion of only one canonical deoxynucleoside triphosphate. The synthesized DNA is treated with an N-glycosylase that excises a base portion of the non-canonical deoxynucleoside triphosphate from the synthesized DNA. The DNA is then treated in such a manner that the phosphodiester backbone of the DNA is broken at the abasic site, thus creating at least two DNA fragments. The fragments are separated according to size.

La présente invention concerne un procédé de caractérisation de molécules d'acide nucléique. Le procédé consiste à synthétiser l'ADN en présence d'un mélange réactionnel comprenant une matrice d'acide nucléique, une molécule amorce, une enzyme développant l'amorce de façon à permettre la synthèse de la molécule d'ADN, quatre désoxynucléoside triphosphates canoniques et au moins un désoxynucléoside triphosphate non canonique. Le désoxynucléoside triphosphate non canonique est incorporé dans l'ADN synthétisé à la place d'une partie d'un seul désoxynucléoside triphosphate canonique. L'ADN synthétisé est traité avec une N-glycosylase qui retranche dans l'ADN synthétisé une partie de base du désoxynucléoside triphosphate non canonique. L'ADN est alors traité de façon à casser le squelette phosphodiester de l'ADN au niveau d'un site abasique, créant ainsi au moins deux fragments d'ADN. La séparation des fragments se fait en fonction de leur taille.

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