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. 1997 Aug 1;25(15):3082–3087. doi: 10.1093/nar/25.15.3082

A coalescent approach to the polymerase chain reaction.

G Weiss 1, A von Haeseler 1
PMCID: PMC146862  PMID: 9224608

Abstract

A versatile algorithm is developed to model PCR on a computer. The method is based on a modification of the coalescent process and provides a general framework to analyse data from PCR. It allows for incorporation of the dynamics of the replication process as described in terms of the number of starting template molecules and cycle-dependent PCR efficiency. The simulation method generates, as a first step, the genealogy of a set of sequences sampled from a final PCR product. In a second step a mutation process is superimposed and the resulting data set is analysed. The efficiency of our algorithm enables us to get reliable approximations of various sample distributions. We demonstrate the relevance of our method with two applications: maximum likelihood estimation of the error rate in PCR and a test of homogeneity of the template.

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Selected References

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  1. Cline J., Braman J. C., Hogrefe H. H. PCR fidelity of pfu DNA polymerase and other thermostable DNA polymerases. Nucleic Acids Res. 1996 Sep 15;24(18):3546–3551. doi: 10.1093/nar/24.18.3546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Donnelly P., Tavaré S., Balding D. J., Griffiths R. C. Estimating the age of the common ancestor of men from the ZFY intron. Science. 1996 May 31;272(5266):1357–1362. doi: 10.1126/science.272.5266.1357. [DOI] [PubMed] [Google Scholar]
  3. Donnelly P., Tavaré S. Coalescents and genealogical structure under neutrality. Annu Rev Genet. 1995;29:401–421. doi: 10.1146/annurev.ge.29.120195.002153. [DOI] [PubMed] [Google Scholar]
  4. Fu Y. X., Li W. H. Estimating the age of the common ancestor of men from the ZFY intron. Science. 1996 May 31;272(5266):1356–1362. doi: 10.1126/science.272.5266.1356. [DOI] [PubMed] [Google Scholar]
  5. Gilliland G., Perrin S., Blanchard K., Bunn H. F. Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2725–2729. doi: 10.1073/pnas.87.7.2725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Griffiths R. C., Tavaré S. Sampling theory for neutral alleles in a varying environment. Philos Trans R Soc Lond B Biol Sci. 1994 Jun 29;344(1310):403–410. doi: 10.1098/rstb.1994.0079. [DOI] [PubMed] [Google Scholar]
  7. Krawczak M., Reiss J., Schmidtke J., Rösler U. Polymerase chain reaction: replication errors and reliability of gene diagnosis. Nucleic Acids Res. 1989 Mar 25;17(6):2197–2201. doi: 10.1093/nar/17.6.2197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Mullis K. B., Faloona F. A. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335–350. doi: 10.1016/0076-6879(87)55023-6. [DOI] [PubMed] [Google Scholar]
  9. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  10. Tamura K., Nei M. Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. Mol Biol Evol. 1993 May;10(3):512–526. doi: 10.1093/oxfordjournals.molbev.a040023. [DOI] [PubMed] [Google Scholar]
  11. Tavaré S. Line-of-descent and genealogical processes, and their applications in population genetics models. Theor Popul Biol. 1984 Oct;26(2):119–164. doi: 10.1016/0040-5809(84)90027-3. [DOI] [PubMed] [Google Scholar]
  12. Watson E., Bauer K., Aman R., Weiss G., von Haeseler A., Päbo S. mtDNA sequence diversity in Africa. Am J Hum Genet. 1996 Aug;59(2):437–444. [PMC free article] [PubMed] [Google Scholar]
  13. Watterson G. A. On the number of segregating sites in genetical models without recombination. Theor Popul Biol. 1975 Apr;7(2):256–276. doi: 10.1016/0040-5809(75)90020-9. [DOI] [PubMed] [Google Scholar]
  14. Weiss G., von Haeseler A. Estimating the age of the common ancestor of men from the ZFY intron. Science. 1996 May 31;272(5266):1359–1362. doi: 10.1126/science.272.5266.1359. [DOI] [PubMed] [Google Scholar]
  15. Weiss G., von Haeseler A. Modeling the polymerase chain reaction. J Comput Biol. 1995 Spring;2(1):49–61. doi: 10.1089/cmb.1995.2.49. [DOI] [PubMed] [Google Scholar]

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