Estimation of genotype error rate using samples with pedigree information - an application on the GeneChip Mapping 10K array

Currently, most analytical methods assume all observed genotypes are correct; however, it is clear that errors may reduce statistical power or bias inference in genetic studies. We propose procedures for estimating error rate in genetic analysis and apply them to study the GeneChip Mapping 10K array, which is a technology that has recently become available and allows researchers to survey over 10,000 SNPs in a single assay. We employed a strategy to estimate the genotype error rate in pedigree data. First, the "dose -response" reference curve between error rate and the observable error number were derived by simulation, conditional on given pedigree structures and genotypes. Second, the error rate was estimated by calibrating the number of observed errors in real data to the reference curve. We evaluated the performance of this method by simulation study and applied it to a data set of 30 pedigrees genotyped using the GeneChip Mapping 10K array. This method performed favorably in all scenarios we surveyed. The dose-response reference curve was monotone and almost linear with a large slope. The method was able to estimate accurately the error rate under various pedigree structures and error models and under heterogeneous error rates. Using this method, we found that the average genotyping error rate of the GeneChip Mapping I OK array was about 0.1%. Our method provides a quick and unbiased solution to address the genotype error rate in pedigree data. It behaves well in a wide range of settings and can be easily applied in other genetic projects. The robust estimation of genotyping error rate allows us to estimate power and sample size and conduct unbiased genetic tests. The GeneChip Mapping I OK array has a low overall error rate, which is consistent with the results obtained from alternative genotyping assays. (C) 2004 Elsevier Inc. All rights reserved.