Genotyping single nucleotide polymorphisms by mass spectrometry

Tost, Jörg; Gut, Ivo

doi:10.1002/mas.1009

Cited by 120 publications

(87 citation statements)

References 201 publications

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“…In 1997, a well-publicized editorial conceded that competitive MS technologies would not be ready to contribute before the then-looming completion of the Human Genome Project, but predicted that a bright future was still in store for genotyping and diagnostic applications [52]. This prediction was realized by the introduction of technologies for the rapid characterization of single nucleotide polymorphisms [53][54][55] and for the detection/identification of infectious pathogens [56 -58]. At the time of this editorial, however, the broader MS community had been already shifting its attention toward the burgeoning field of MS-based proteomics [59 -61].…”

Section: Making Headways In Biomedical Researchmentioning

confidence: 99%

A eole for the MS analysis of nucleic acids in the post-genomics age

Fabris

2010

J. Am. Soc. Mass Spectrom.

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The advances of mass spectrometry in the analysis of nucleic acids have tracked very closely the exciting developments of instrumentation and ancillary technologies, which have taken place over the years. However, their diffusion in the broader life sciences community has been and will be linked to the ever evolving focus of biomedical research and its changing demands. Before the completion of the Human Genome Project, great emphasis was placed on sequencing technologies that could help accomplish this project of exceptional scale. After the publication of the human genome, the emphasis switched toward techniques dedicated to the exploration of sequences not coding for actual protein products, which amount to the vast majority of transcribed elements. The broad range of capabilities offered by mass spectrometry is rapidly advancing this platform to the forefront of the technologies employed for the structure-function investigation of these noncoding elements. Increasing focus on the characterization of functional assemblies and their specific interactions has prompted a re-evaluation of what has been traditionally construed as nucleic acid analysis by mass spectrometry. Inspired by the accelerating expansion of the broader field of nucleic acid research, new applications to fundamental biological studies and drug discovery will help redefine the evolving role of MS-analysis of nucleic acids in the post-genomics age. (J Am Soc Mass Spectrom 2010, 21, 1-13)

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Section: Making Headways In Biomedical Researchmentioning

confidence: 99%

A eole for the MS analysis of nucleic acids in the post-genomics age

Fabris

2010

J. Am. Soc. Mass Spectrom.

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“…Therefore, MALDI-TOF MS in combination with a minisequencing strategy has become one of the most promising mutation analysis tools to analyze polymorphisms in disease-causing genes, including the genes encoding cystic fibrosis (Braun et al 1997), coronary artery diseases (Nakai et al 2002), cardiovascular disease, and even the disease-causing mutations on human Y chromosome (Paracchini et al 2002;Wise et al 2003). Compared with other DNA analysis methods, the advantages of MALDI-TOF MS include the direct and absolute mass readout of DNA (Tost and Gut 2002) and high-throughput analysis (Van Ausdall and Marshall 1998) that facilitates simultaneous multiplex genotyping in a single experiment.…”

Section: Introductionmentioning

confidence: 99%

“…The limitations are based on the following factors: (1) difficult and time-consuming optimization of multiplex primer extension (Tost and Gut 2002), and (2) spectral interference from contaminating salt adducts (Guo 1999;Tost and Gut 2002). The former issue presents a specific challenge because highly multiplex genotyping parameters may be difficult to optimize.…”

Section: Introductionmentioning

confidence: 99%

“…The genotyping of these closely associated and clustered mutations within the b-thalassemia gene poses practical difficulty for multiplex minisequencing in a single tube . The second limiting factor for multiplex HBB genotyping using MALDI-TOF MS is that contaminating salt, detergent, or glycerol can degrade spectral quality and reduce the accuracy of mass assignment (Bleicher and Bayer 1994;Guo 1999;Kim et al 2002;Tost and Gut 2002). In a highly multiplex assay, this increase in interference is greater than the linear scale of the multiplex factor.…”

Section: Introductionmentioning

confidence: 99%

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Parallel minisequencing followed by multiplex matrix-assisted laser desorption/ionization mass spectrometry assay for β-thalassemia mutations

Liao

Kao³

et al. 2005

J Hum Genet

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b-thalassemia is a common monogenic disease caused by mutations in the human b-globin gene (HBB), many of which are differentially represented in human subpopulations stratified by ethnicity. This study describes an efficient and highly accurate method to screen for the eight most-common disease-causing mutations, covering more than 98% of HBB alleles in the Taiwanese population, using parallel minisequencing and multiplex assay by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The MALDI-TOF MS was optimized for sensitivity and resolution by ''mass tuning'' the PinPoint assay for eight HBB SNPs. Because of the close proximity and clustering of mutations in HBB, primer extension reactions were conducted in parallel. Efficient sequential desalting using POROS and cationic exchange chromatography allowed for an unambiguous multiplex genotyping by MALDI-TOF MS. The embellishing SNP assay allowed for highly accurate identification of the eight most-common b-thalassemia mutations in homozygous normal control, carrier, and eight heterozygous carrier mixtures, as well as the diagnosis of a high-risk family. The results demonstrated a flexible strategy for rapid identification of clustering SNPs in HBB with a high degree of accuracy and specificity. It can be adapted easily for high-throughput diagnosis of various hereditary diseases or to establish family heritage databases for clinical applications.

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“…Hence, a considerable number of different methodologies for screening for polymorphisms and for determining individual allelic states have been developed, which have been reviewed recently [6,7]. Matrix-assisted laser desorption/ionization mass spectrometry MALDI-MS [8,9] and electrospray ionization mass spectrometry (ESI-MS) [10 -12] have been successfully applied to the investigation of sequence variations in nucleic acids.…”

mentioning

confidence: 99%

Applicability of tandem mass spectrometry to the automated comparative sequencing of long-chain oligonucleotides

Oberacher¹,

Parson²,

Oefner³

et al. 2004

J. Am. Soc. Mass Spectrom.

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An algorithm for the comparative sequencing (COMPAS) of oligonucleotides is shown to be suitable for the sequence verification of nucleic acids ranging in length from a few to 80 nucleotides. The algorithm is based on the matching of a fragment ion spectrum generated by collision-induced dissociation to m/z values predicted from a known reference sequence employing established fragmentation pathways. Prior to mass spectrometric investigation, the oligonucleotides were on-line purified by ion-pair reversed-phase high-performance liquid chromatography using monolithic separation columns. This study evaluated the potential and the limits of COMPAS regarding the length and the charge state of oligonucleotides, the selected collision energy, and the analyzed amount of sample using a quadrupole ion trap mass spectrometer. The results revealed that oligonucleotides could be very reliably resequenced up to 60-mers, although the algorithm was successfully used to even verify sequences up to 80-mers. The relative collision energy was typically in the range between 13 and 20%, which allowed in most cases a verification of the reference sequence in a window of at least three consecutive collision energies. To select a proper charge state for fragmentation, a compromise had to be found between high signal intensity and low charge state. Furthermore, by reducing the eluent flow rate during elution of the oligonucleotide, the sequence of a 50-mer was successfully verified from the analysis of 295 fmol of the raw product. COMPAS was proven to be reproducible and was applied to the genotyping of the polymorphic, Y-chromosomal locus M9 contained in a 62-base pair polymerase chain reaction product. (J Am Soc Mass Spectrom 2004, 15, 510 -522)

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Genotyping single nucleotide polymorphisms by mass spectrometry

Cited by 120 publications

References 201 publications

A eole for the MS analysis of nucleic acids in the post-genomics age

A eole for the MS analysis of nucleic acids in the post-genomics age

Parallel minisequencing followed by multiplex matrix-assisted laser desorption/ionization mass spectrometry assay for β-thalassemia mutations

Applicability of tandem mass spectrometry to the automated comparative sequencing of long-chain oligonucleotides

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