Archives of Toxicology

, Volume 82, Issue 4, pp 265–270 | Cite as

Reconstruction of N-acetyltransferase 2 haplotypes using PHASE

  • Klaus Golka
  • Meinolf Blaszkewicz
  • Mirabutaleb Samimi
  • Hermann M. Bolt
  • Silvia Selinski
Short Communication


The genotyping of N-acetyltransferase 2 (NAT2) by PCR/RFLP methods yields in a considerable percentage ambiguous results. To resolve this methodical problem a statistical approach was applied. PHASE v2.1.1, a statistical program for haplotype reconstruction was used to estimate haplotype pairs from NAT2 genotyping data, obtained by the analysis of seven single nucleotide polymorphisms relevant for Caucasians. In 1,011 out of 2,921 (35%) subjects the haplotype pairs were clearcut by the PCR/RFLP data only. For the majority of the data the applied method resulted in a multiplicity (2–4) of possible haplotype pairs. Haplotype reconstruction using PHASE v2.1.1 cleared this ambiguity in all cases but one, where an alternative haplotype pair was considered with a probability of 0.029. The estimation of the NAT2 haplotype is important because the assignment of the NAT2 alleles *12A, *12B, *12C or *13 to the rapid or slow NAT2 genotype has been discussed controversially. A clear assignment is indispensable in surveys of human bladder cancer caused by aromatic amine exposures. In conclusion, PHASE v2.1.1 software allowed an unambiguous haplotype reconstruction in 2,920 of 2,921 cases (>99.9%).


PHASE v2.1.1 NAT2 genotyping Single nucleotide polymorphism Haplotype reconstruction 



The financial support of the Deutsche Forschungsgemeinschaft (SFB 475, “Reduction of complexity in multivariate data structures”) is gratefully acknowledged. Many thanks are due to Doris Dannappel for her excellent technical assistance and to Heinz Dieter Giller for his introduction into the DOS editor.


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Klaus Golka
    • 1
  • Meinolf Blaszkewicz
    • 1
  • Mirabutaleb Samimi
    • 1
  • Hermann M. Bolt
    • 1
  • Silvia Selinski
    • 1
    • 2
  1. 1.Institute for Occupational Physiology at the University of Dortmund (IfADo)DortmundGermany
  2. 2.Department of StatisticsUniversity of DortmundDortmundGermany

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