Quantitative Detection of Low-Copy-Number mRNAs Differing at Single Nucleotide Positions

Accurate analysis of mRNA expression levels of SNPs, highly homologous genes, and splicing variants requires techniques capable of quantifying low-copy-number mRNAs differing at single nucleotide positions. We have used an RT-PCR-based technique based on co-amplification of closely related target mR...

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Main Authors: J. Stenman, S. Lintula, O. Rissanen, P. Finne, J. Hedström, A. Palotie, A. Orpana
Format: Article
Language:English
Published: Taylor & Francis Group 2003-01-01
Series:BioTechniques
Online Access:https://www.future-science.com/doi/10.2144/03341dd05
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author J. Stenman
S. Lintula
O. Rissanen
P. Finne
J. Hedström
A. Palotie
A. Orpana
author_facet J. Stenman
S. Lintula
O. Rissanen
P. Finne
J. Hedström
A. Palotie
A. Orpana
author_sort J. Stenman
collection DOAJ
description Accurate analysis of mRNA expression levels of SNPs, highly homologous genes, and splicing variants requires techniques capable of quantifying low-copy-number mRNAs differing at single nucleotide positions. We have used an RT-PCR-based technique based on co-amplification of closely related target mRNA transcripts and assessed the effect of the stochastic distribution of low-copy-number templates on sampling variation when quantifying rare mRNA transcripts. The technique was optimized for maximal sensitivity to enable the analysis of samples containing a subpopulation of target cells and small microdissected samples. We demonstrate that the input level of template molecules is a critical determinant of the achievable assay precision. A minimum of approximately 50 molecules of template is required to discriminate between 2-fold differences in the expression levels of two transcripts. At levels above 1000 molecules of input template, the stochastic effects on sampling variation become negligible.
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spelling doaj-art-b0b21cff41794516a7c25dedb262f0d42025-08-20T02:25:50ZengTaylor & Francis GroupBioTechniques0736-62051940-98182003-01-0134117217710.2144/03341dd05Quantitative Detection of Low-Copy-Number mRNAs Differing at Single Nucleotide PositionsJ. Stenman0S. Lintula1O. Rissanen2P. Finne3J. Hedström4A. Palotie5A. Orpana61Helsinki University Central Hospital, Helsinki, Finland1Helsinki University Central Hospital, Helsinki, Finland1Helsinki University Central Hospital, Helsinki, Finland1Helsinki University Central Hospital, Helsinki, Finland1Helsinki University Central Hospital, Helsinki, Finland1Helsinki University Central Hospital, Helsinki, Finland1Helsinki University Central Hospital, Helsinki, FinlandAccurate analysis of mRNA expression levels of SNPs, highly homologous genes, and splicing variants requires techniques capable of quantifying low-copy-number mRNAs differing at single nucleotide positions. We have used an RT-PCR-based technique based on co-amplification of closely related target mRNA transcripts and assessed the effect of the stochastic distribution of low-copy-number templates on sampling variation when quantifying rare mRNA transcripts. The technique was optimized for maximal sensitivity to enable the analysis of samples containing a subpopulation of target cells and small microdissected samples. We demonstrate that the input level of template molecules is a critical determinant of the achievable assay precision. A minimum of approximately 50 molecules of template is required to discriminate between 2-fold differences in the expression levels of two transcripts. At levels above 1000 molecules of input template, the stochastic effects on sampling variation become negligible.https://www.future-science.com/doi/10.2144/03341dd05
spellingShingle J. Stenman
S. Lintula
O. Rissanen
P. Finne
J. Hedström
A. Palotie
A. Orpana
Quantitative Detection of Low-Copy-Number mRNAs Differing at Single Nucleotide Positions
BioTechniques
title Quantitative Detection of Low-Copy-Number mRNAs Differing at Single Nucleotide Positions
title_full Quantitative Detection of Low-Copy-Number mRNAs Differing at Single Nucleotide Positions
title_fullStr Quantitative Detection of Low-Copy-Number mRNAs Differing at Single Nucleotide Positions
title_full_unstemmed Quantitative Detection of Low-Copy-Number mRNAs Differing at Single Nucleotide Positions
title_short Quantitative Detection of Low-Copy-Number mRNAs Differing at Single Nucleotide Positions
title_sort quantitative detection of low copy number mrnas differing at single nucleotide positions
url https://www.future-science.com/doi/10.2144/03341dd05
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