Mapping of genes involved in rare recessive diseases is usually difficult because of the lack of families with more than one affected progeny. The problem may be avoided by using inbred affected individuals and the strategy of homozygosity mapping.

In practice, the use of homozygosity mapping in a genome-wide scan requires that a set of markers regularly spaced and spanning the whole genome are tested. Investigators are then faced to the problem of choosing the spacing of markers.

To help solve this problem, we give some useful clues by computing (1) the expected length of the region of identity by descent around the disease locus, (2) the distribution, given the spacing of markers, of the number of affected individuals expected not to be homozygous at the marker closest to the disease locus and, (3) the expected type-one error. We show that even if the markers are very closely spaced, it is not unlikely that some affected individuals in the sample will not be homozygous at the marker closest to the disease locus. Excluding a region by the criterion that all affected individuals in the sample are not homozygous may then dramatically increase the rate of false negatives. We thus propose to relax the criterion to declare a region candidate, based on the sample size and the spacing of markers.