Detection of genotyping errors by Hardy-Weinberg equilibrium testing

Eur J Hum Genet. 2004 May;12(5):395-9. doi: 10.1038/sj.ejhg.5201164.


Genotyping data sets may contain errors that, in some instances, lead to false conclusions. Deviation from Hardy-Weinberg equilibrium (HWE) in random samples may be indicative of problematic assays. This study has analysed 107,000 genotypes generated by TaqMan, RFLP, sequencing or mass spectrometric methods from 443 single-nucleotide polymorphisms (SNPs). These SNPs are distributed both within genes and in intergenic regions. Genotype distributions for 36 out of 313 assays (11.5%) whose minor allele frequencies were >0.05 deviated from HWE (P<0.05). Some of the possible reasons for this deviation were explored: assays for five SNPs proved nonspecific, and genotyping errors were identified in 21 SNPs. For the remaining 10 SNPs, no reasons for deviation from HWE were identified. We demonstrate the successful identification of a proportion of nonspecific assays, and assays harbouring genotyping error. Consequently, our current high-throughput genotyping system incorporates tests for both assay specificity and deviation from HWE, to minimise the genotype error rate and therefore improve data quality.

MeSH terms

  • DNA / chemistry
  • DNA / genetics
  • Gene Frequency
  • Genotype
  • Humans
  • Linkage Disequilibrium / genetics*
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide / genetics*
  • Sequence Analysis, DNA / methods
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • DNA