A powerful and rapid approach to human genome scanning using small quantities of genomic DNA

Dense maps of short-tandem-repeat polymorphisms (STRPs) have allowed genome -wide searches for genes involved in a great variety of diseases with genet ic influences, including common complex diseases. Generally for this purpos e, marker sets with a 10 cM spacing are genotyped in hundreds of individual s. We have performed power simulations to estimate the maximum possible int er-marker distance that still allows for sufficient power. In this paper we further report on modifications of previously published protocols, resulti ng 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 mul tiplex 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 statis tical analysis of a set of chromosomes, as sets of chromosomes are being ge notyped. A genome scan following this modified protocol can be performed us ing a maximum amount of 2.5 mug of genomic DNA per individual, isolated fro m either blood or from mouth swabs.