Multiplex PCR primer design for gene family using genetic algorithm

ABSTRACT

The multiplex PCR experiment is to amplify multiple regions of a DNA sequence at the same time by using different primer pairs. Designing feasible primer pairs for multiplex PCR is a tedious task since there are too many constraints to be satisfied. In this paper, a new method for multiplex PCR primer design strategy using genetic algorithm is proposed. The proposed algorithm is able to find a set of suitable primer pairs more efficient and uses a MAP model to speed up the examination of the specificity constraint that is important for gene family sequences. The dry-dock experiment shows that the proposed algorithm finds several sets of primer pairs of gene family sequences for multiplex PCR that not only obey the design properties, but also have specificity.

REFERENCES

• 1: McPherson, M. J., Quirke, P. and Taylor, G. R. PCR: A Practical Approach. Oxford University Press, New York, 1993
• 2: Singh, V. K., Mangalam, A. K., Dwived, S. and Naik, S. Primer premier?Program for design of degenerate primers form a protein sequence. BioTechniques, 24, 1998, 318--319.
• 3: Lincoln, S. E., Daly, M. J. and Lander, E. S. PRIMER: A Computer Program for Automatically Selecting PCR Primers. MIT Center for Genome Research and Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, 1991.
• 4: Nicodème, P. A computer support for genotyping by multiplex PCR. Technical Report LIX/RR/93/09, LIX, Ecole Polytechnique, 91128, Palaiseau Cedex, France, 1993.
• 5: Pierre Nicodème , Jean-Marc Steyaert, Selecting Optimal Oligonucleotide Primers for Multiplex PCR, Proceedings of the 5th International Conference on Intelligent Systems for Molecular Biology, p.210-213, June 21-26, 1997
• 6: Schoske, R. , Vallone, P. M., Ruitberg, C. M. and Butler, J. M. Multiplex PCR design strategy used for the simultaneous amplification of 10 Y chromosome short tandem repeat (STR) loci. Anal. Bioanal. Chem., 375, 2003, 333--343.
• 7: Kämpke, T., Kieninger, M. and Mecklenburg, M. Efficient primer design algorithms, Bioinformatics, 17, 2001, 214--225.
• 8: David E. Goldberg, Genetic Algorithms in Search, Optimization and Machine Learning, Addison-Wesley Longman Publishing Co., Inc., Boston, MA, 1989
• 9: Jain-Shing Wu , Chungnan Lee , Chien-Chang Wu , Yow-Ling Shiue, Primer design using genetic algorithm, Bioinformatics, v.20 n.11, p.1710-1717, July 2004 [doi>10.1093/bioinformatics/bth147]
• 10: Arbour, N. C., Lorenz, E., Schutte, B. C., Zabner, J., Kline, J. N., Jones, M., Frees, K., Watt, J. L., and Schwartz, D. A. A genetics basis for a blunted response to endotoxin in Humans, 2000. http://www.ncbi.nlm.nih.gov/entrez/

INDEX TERMS

Primary Classification:
  J. Computer Applications
  J.3 LIFE AND MEDICAL SCIENCES
      Subjects: Biology and genetics

General Terms:
Experimentation

Keywords:
genetic algorithm, multiplex PCR, primer design