title: Identification of probable genotyping errors by consideration of haplotypes.
abstract: Undetected genotyping errors pose a problem in genetic epidemiological studies, as they may invalidate statistical analysis or reduce its power. Haplotype analysis requires an improved standard of the data, because a haplotype can be inferred correctly only if the genotypes of all its markers are correct. Here, we present a method that identifies probable genotyping errors in trio samples with the help of the estimated haplotype frequency distribution of the sample. If the likelihood of the most likely haplotype explanation depends strongly on just one genotype, in the sense that setting the genotype to be missing leads to a much more likely haplotype explanation, this genotype is considered as a potential genotyping error. We describe a method that systematically searches the whole data set for such potential errors. Based on the haplotype distribution of a real data set, we carry out a simulation study to estimate the sensitivity and specificity of the method. In addition, we apply our approach to the real data set itself. Potentially erroneous genotypes are re-determined via sequencing. The results of both the simulation study and of the application to the real data set show that a considerable proportion of true genotyping errors is detected and that the number of false-positive signals is acceptable. We conclude that it is indeed possible to identify probable genotyping errors by considering haplotypes. The method described here will be part of the next release of our FAMHAP software.
authors.affiliation: Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Becker
authors.forename: Ruta
authors.initials: R
authors.lastname: Valentonyte
authors.forename: Peter J P
authors.initials: PJ
authors.lastname: Croucher
authors.forename: Konstantin
authors.initials: K
authors.lastname: Strauch
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
authors.forename: Michael
authors.initials: M
authors.lastname: Knapp
mesh_terms: D003198:Computer Simulation; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008957:Models, Genetic; D011237:Predictive Value of Tests; D012107:Research Design
chemical_list: D005819:Genetic Markers