HOW TO TACKLE GENETIC-LOCI PREDISPOSING TO ATHEROSCLEROSIS

To identify major genes influencing the complex disease process of ath erosclerosis, the strategy for collection of study materials should be designed with care to enrich the genetic factors. The tools for an ef ficient gene search are provided by the Human Genome Program; current genetic maps with dense marker sets provide a basis for genome-wide sc ans, and close to complete physical maps and identification of coding regions of all human genes within next few years offer the scaffolding for the final recognition of genes predisposing to atherosclerosis. T he statistical methods applicable in the initial gene search of comple x diseases have developed during recent years including now exact modi fications of association analysis, also advanced multipoint analyses a pplicable in both parametric (linkage analysis) and nonparametric (aff ected sib-pair) methods and maximizing the information extractable fro m individual genotypes. Genome scans in the relevant animal models wil l often guide to important genomic regions, and genetically modified a nimals will be of essential importance for final understanding of the molecular pathogenesis of atherosclerosis.