ERROR DETECTION IN GENETIC LINKAGE DATA FOR HUMAN PEDIGREES USING LIKELIHOOD RATIO METHODS

Abstract

The occurrence of laboratory typing error in pedigree data collected for use in linkage analysis cannot be ignored. In maps where recombinations between nearby markers rarely occur, each erroneous recombinations (result of typing error) is given substantial weight thereby increasing the estimate of θ, the recombination fraction. As the maps being developed become more dense, θ approaches the error rate and most of all observed crossovers will be erroneous. We present a method for detecting errors in pedigree data. The index is a variant of the likelihood ratio test statistic and is used to test the null hypothesis of no error for an individual at a locus versus the alternative hypothesis of error. High values of the index correspond to unlikely genotypes. The method has been shown to detect errors introduced into CEPH pedigrees and an error in a larger experimental pedigree (retinitis pigmentosa). While the method was designed to detect typing error, it is sufficiently general to detect any relatively unlikely genotype and therefore can also be used to detect pedigree error.