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.