The minimum physical distance surrounding a candidate gene has been determined in founder populations by studying allele sharing and then mapping historical recombination events. In this study, we developed a novel minimalistic approach by using the genetically isolated population of Tasmania, Australia, to identify candidate gene loci in a small number of individuals of unknown genetic relationship affected by a dominant disorder. Keratoconus, an inheritable non-inflammatory progressive degeneration of the cornea, is present at a five-fold increased incidence in Burnie, a coastal town on the island of Tasmania. Based on the fundamental assumption that individuals with keratoconus from this town are likely to be related through a founder effect, a 10-cM interval genome scan was conducted on six patients of undefined genetic relationship and one affected sib-pair to identify commonly shared chromosomal segments for the elucidation of candidate gene loci. Analysis of allele sharing revealed four markers on three chromosomes where all eight individuals shared a common allele on at least one chromosome, and thirteen markers where all but one patient shared common alleles. No excess of allele sharing was observed at any marker tested on chromosome 21, a suggested candidate chromosome for keratoconus. Further analysis of positive loci revealed suggestive association at 20q12, where significant deviation in allele frequency D20S119 ( P=2.1 x 10(-5)) is observed when additional Tasmanian keratoconus samples are genotyped. Identification of a conserved minimal chromosomal haplotype around D20S119 in related Tasmanian patients suggests association with this locus, however association with the nearby candidate gene MMP-9 has been excluded.