Locus ordering based on crossover information in family haplotypes: application of a "minimum break" algorithm

A "minimum break" method, previously applied to radiation hybrid data, is applied to the Genetic Analysis Workshop 12 simulated family data to assess the method's feasibility for ordering dense markers that have been typed in a set of pedigrees of three or more generations. Ordering is based on minimizing the total number of crossovers ("breaks") in a set of haplotypes where allele origin can be assigned to each specific haplotype, but locus order is unknown. It is shown that, for average locus spacing of about 2 cM and a set of 300 to 600 haplotypes, locus ordering can be reliably determined for sets of at least 50 loci. However, in the absence of crossovers between some pairs (sets) of loci, no unique order can be identified and sets of orders that are equally likely will be recovered. The method presented can be used to obtain reasonable sets of ordered loci that can then be used by other methods to refine the statistical confidence of the locus order.