Multipoint estimation of identity-by-descent probabilities at arbitrary positions among marker loci on general pedigrees

Objectives:To describe, implement, and test an efficient algorithm to obtai n multipoint identity-by-descent (IBD) probabilities at arbitrary positions among marker loci for general pedigrees. Unlike existing programs, our alg orithm can analyze data sets with large numbers of people and markers. The algorithm has been implemented in the SimWalk2 computer package. Methods: U sing a rigorous testing regimen containing five pedigrees of various sizes with realistic marker data, we compared several widely used IBD computation programs: Allegro, Aspex, GeneHunter, MapMaker/Sibs, Mendel, Sage, SimWalk 2, and Solar. Results:The testing revealed a few discrepancies, particularl y on consanguineous pedigrees, but overall excellent results in the determi nistic multipoint packages. SimWalk2 was also found to be in good agreement with the deterministic multipoint programs, usually matching to two decima l places the kinship coefficient that ranges from 0 to 1. However, the pack ages based on single-point IBD estimation, while consistent with each other , often showed poor results, disagreeing with the multipoint kinship result s by as much as 0.5. Conclusions: Our testing has clearly shown that multip oint IBD estimation is much better than single-point estimation. In additio n, our testing has validated our algorithm for estimating IBD probabilities at arbitrary positions on general pedigrees. Copyright (C) 2001 S. Karger AG, Basel.