title: Comparative study of multipoint methods for genotype error detection.
abstract: Several programs are currently available for the detection of genotyping error that may or may not be Mendelianly inconsistent. However, no systematic study exists that evaluates their performance under varying pedigree structures and sizes, marker spacing, and allele frequencies. Our simulation study compares four multipoint methods: Merlin, Mendel4, SimWalk2, and Sibmed. We look at empirical thresholds, power, and false-positive rates on 7 small pedigree structures that included sibships with and without genotyped parents, and a three-generation pedigree, using 11 microsatellite markers with 3 different map spacings. Simulated data includes 5,000 replicates of each pedigree structure and marker map, with random genotyping errors in about 4% of the middle marker's genotypes. We found that the default thresholds used by these programs provide low power (47-72%). Power is improved more by adding genotyped siblings than by using more closely spaced markers. Some mistyping methods are sensitive to the frequencies of the observed alleles. Siblings of mistyped individuals have elevated false-positive rates, as do markers close to the mistyped marker. We conclude that thresholds should be decided based on the pedigree and marker data and that greater focus should be placed on modeling genotyping error when computing likelihoods, rather than on detecting and eliminating genotyping errors.
authors.affiliation: Department of Human Genetic, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Nandita
authors.initials: N
authors.lastname: Mukhopadhyay
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Buxbaum
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Weeks
mesh_terms: D000483:Alleles; D002874:Chromosome Mapping / Q000379:methods; D005189:False Positive Reactions; D005787:Gene Frequency; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats; D008957:Models, Genetic; D010375:Pedigree; D015203:Reproducibility of Results