Genome scanning for segments shared identical by descent among distant relatives in isolated populations

Abstract

In this paper, we address some of the statistical issues concerning false-positive rates that arise when the whole genome, or a portion thereof, is scanned in distantly related individuals, to search for a disease locus. We derive a method for correcting false-positive probabilities for the large number of comparisons that are performed when scanning a large portion of the genome. We consider both the idealized situation of a dense set of fully informative markers and the more realistic datacollection strategy of an initial scan at low resolution to identify promising areas, which then are typed with markers at high resolution. We also examine the accuracy of false- positive rates approximated using a conservative estimate of the separation distance between affected individuals in the current generation and the common ancestral couple. Calculation of false-positive rates when inbreeding is present in the pedigree also is considered.