Detection of genotyping errors by Hardy–Weinberg equilibrium testing

Genotypingdata sets may contain errors that, in some instances, lead to false conclusions. Deviationfrom Hardy-Weinberg equilibrium (HWE) in random samples may be indicative of problematic assays. This study has analysed 107000 genotypesgenerated by TaqMan, RFLP, sequencing or mass spectrometric methods from 443 single-nucleotide polymorphisms ( SNPs). These SNPsare distributed both within genes and in intergenic regions. Genotypedistributions for 36 out of 313 assays (11.5%) whose minor allele frequencieswere >0.05 deviatedfrom HWE (P<0.05). Some of the possible reasons for this deviationwere explored: assays for five SNPsproved nonspecific, and genotypingerrors were identified in 21 SNPs. For the remaining 10 SNPs, no reasons for deviationfrom HWE were identified. We demonstrate the successful identification of a proportion of nonspecific assays, and assays harbouring genotypingerror. Consequently, our current high-throughput genotypingsystem incorporates tests for both assay specificity and deviationfrom HWE, to minimise the genotypeerror rate and therefore improve data quality.