Quantitative Approach to Single-Nucleotide Polymorphism Analysis Using MALDI-TOF Mass Spectrometry

Pooling of DNA samples before genotyping is a valuable means of streamlining large-scale genotyping efforts in disease association studies, single-nucleotide polymorphism (SNP) validation or mutant allele screening programs. In this report, we explore the application of matrix-assisted laser desorpt...

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Main Authors: Philip Ross, Laura Hall, Lawrence A. Haff
Format: Article
Language:English
Published: Taylor & Francis Group 2000-09-01
Series:BioTechniques
Online Access:https://www.future-science.com/doi/10.2144/00293rr05
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author Philip Ross
Laura Hall
Lawrence A. Haff
author_facet Philip Ross
Laura Hall
Lawrence A. Haff
author_sort Philip Ross
collection DOAJ
description Pooling of DNA samples before genotyping is a valuable means of streamlining large-scale genotyping efforts in disease association studies, single-nucleotide polymorphism (SNP) validation or mutant allele screening programs. In this report, we explore the application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to quantitative analysis of SNPs. The measurements are based on MALDI-TOF MS analysis of primer extension assays performed on standard mixtures of pooled PCR products at several test loci. The inherent high molecular weight resolution of MALDI-TOF MS conveys high specificity and good signal-to-noise ratio for performing accurate quantitation. The methods described maximize the sensitivity and quantitative capacity of MALDI-TOF MS while preserving the throughput and economic advantages of the MALDI-TOF platform. Using the format described, we demonstrate that allele frequencies as low as 5% can be detected quantitatively and unambiguously.
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spelling doaj-art-06a85e71210d4ae9bf39c9ea3733a47d2025-08-20T02:26:06ZengTaylor & Francis GroupBioTechniques0736-62051940-98182000-09-0129362062910.2144/00293rr05Quantitative Approach to Single-Nucleotide Polymorphism Analysis Using MALDI-TOF Mass SpectrometryPhilip Ross0Laura Hall1Lawrence A. Haff21Applied Biosytems, Framingham, MA, USA1Applied Biosytems, Framingham, MA, USA1Applied Biosytems, Framingham, MA, USAPooling of DNA samples before genotyping is a valuable means of streamlining large-scale genotyping efforts in disease association studies, single-nucleotide polymorphism (SNP) validation or mutant allele screening programs. In this report, we explore the application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to quantitative analysis of SNPs. The measurements are based on MALDI-TOF MS analysis of primer extension assays performed on standard mixtures of pooled PCR products at several test loci. The inherent high molecular weight resolution of MALDI-TOF MS conveys high specificity and good signal-to-noise ratio for performing accurate quantitation. The methods described maximize the sensitivity and quantitative capacity of MALDI-TOF MS while preserving the throughput and economic advantages of the MALDI-TOF platform. Using the format described, we demonstrate that allele frequencies as low as 5% can be detected quantitatively and unambiguously.https://www.future-science.com/doi/10.2144/00293rr05
spellingShingle Philip Ross
Laura Hall
Lawrence A. Haff
Quantitative Approach to Single-Nucleotide Polymorphism Analysis Using MALDI-TOF Mass Spectrometry
BioTechniques
title Quantitative Approach to Single-Nucleotide Polymorphism Analysis Using MALDI-TOF Mass Spectrometry
title_full Quantitative Approach to Single-Nucleotide Polymorphism Analysis Using MALDI-TOF Mass Spectrometry
title_fullStr Quantitative Approach to Single-Nucleotide Polymorphism Analysis Using MALDI-TOF Mass Spectrometry
title_full_unstemmed Quantitative Approach to Single-Nucleotide Polymorphism Analysis Using MALDI-TOF Mass Spectrometry
title_short Quantitative Approach to Single-Nucleotide Polymorphism Analysis Using MALDI-TOF Mass Spectrometry
title_sort quantitative approach to single nucleotide polymorphism analysis using maldi tof mass spectrometry
url https://www.future-science.com/doi/10.2144/00293rr05
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