Genome screening by searching for shared segments: mapping a gene for benign recurrent intrahepatic cholestasis.

It is now feasible to map disease genes by screening the genome for linkage disequilibrium between the disease and marker alleles. This report presents the first application of this approach for a previously unmapped locus. A gene for benign recurrent intrahepatic cholestasis (BRIC) was mapped to chromosome 18 by searching for chromosome segments shared by only three distantly related patients. The screening results were confirmed by identifying an extended haplotype conserved between the patients. Probability calculations indicate that such segment sharing is unlikely to arise by chance. Searching the genome for segments shared by patients is a powerful empirical method for mapping disease genes. Computer simulations suggest that, in appropriate populations, the approach may be used to localize genes for common diseases.