Dense maps of short-tandem-repeat polymorphisms (STRPs) have allowed genome-wide searches
for genes involved in a great variety of diseases with genetic influences, including common complex
diseases. Generally for this purpose, marker sets with a 10 cM spacing are genotyped in hundreds
of individuals. We have performed power simulations to estimate the maximum possible inter-marker distance that still allows for sufficient power. In this paper we further report on
modifications of previously published protocols, resulting in a powerful screening set containing
229 STRPs with an average spacing of 18·3 cM. A complete genome scan using our protocol
requires only 80 multiplex PCR reactions which are all carried out using one set of conditions and
which do not contain overlapping marker allele sizes. The multiplex PCR reactions are grouped by
sets of chromosomes, which enables on-line statistical analysis of a set of chromosomes, as sets of
chromosomes are being genotyped. A genome scan following this modified protocol can be
performed using a maximum amount of 2·5 μg of genomic DNA per individual, isolated from
either blood or from mouth swabs.