Abstract: The present invention is directed to an improved analysis procedure for the comparative sequencing of nucleic acids using multistage mass spectrometry. More precisely, the invention is directed to a method enabling the de-novo sequencing of nucleic acid molecules using multistage mass spectrometry.

Abstract: A method for the identification of DNA sequence elements in complex and highly variable sequences is described. The method consists of identifying a short sequence element of several DNA bases (2-6 bases) at a given position in the genome simultaneously on all parental alleles. The method allows differentiating mini-haplotypes on different alleles in one analysis. The method consists of carrying out an enzymatic primer extension reaction with a combination of extension primers (pool of primers) and analysing the products by mass spectrometry. The pool of primers is assembled in such a way that the primer extension product allows unambiguous identification of both the primer of the pool that was extended and the base that was added. The method is of great utility for DNA sequences harbouring many SNPs close to each other with many possible haplotypes. Such sequences are known in the Major Histocompatibility Complex (MHC).

Abstract: A method for the detection in a given DNA sequence of DNA mutations, single nucleotide polymorphisms, and insertions and deletions, said method comprising the step of a) producing replicate(s) with an engineered polymerase of said given DNA sequence with part or all of at least one of the four natural DNA bases exchanged against a not natural base; b) using said not natural base to cleave the replicate(s) obtained in step a) and to produce a DNA product presenting sequence-specific fragments; c) analyzing said sequence-specific fragments obtained in step b) by mass spectrometry to get sequence-specific fragment patterns; and d) using the sequence-specific fragment patterns obtained in step c) to identify sequence changes relative to a reference to said given DNA sequence. A kit for the detection of DNA mutations, single nucleotide polymorphisms, and insertions and deletions.

Abstract: The present invention is directed to an improved analysis procedure for the comparative sequencing of nucleic acids using multistage mass spectrometry. More precisely, the invention is directed to a method enabling the de-novo sequencing of nucleic acid molecules using multistage mass spectrometry.

Abstract: The invention relates to a method for performing haplotyping of multiple single nucleotide polymorphisms (SNPs) that uses allele specific PCR and mass spectrometry analysis.