Complete genomic screen for disease susceptibility loci in nuclear families

We performed genome-wide model dependent and independent analyses on a simu lated data set of 400 families segregating for a rare disorder. Regions on chromosomes 1, 3, and 5 were consistently indicated across the various anal yses performed. Follow-up analyses included stratification for locus hetero geneity and clinical phenotype and studies of gene x gene and gene x enviro nment interaction. The region around D1G024 was most notable, showing stron g association and linkage with the trait. We also identified regions D3G043 -46 and D5G037-39 by strong linkage and association findings and region DIG 001-09 by linkage analysis. A complex statistical interaction was suggested between D1G024, D3G046 and environmental factor 1. This report suggests th at traditional methods of analysis can be implemented to analyze and descri be the mechanisms that may underlie the more complex genetic disorders. (C) 1999 Wiley-Liss, Inc.