SCANNING THE GENOME FOR ESSENTIAL-HYPERTENSION LOCI

1. Essential hypertension occurs in people with an underlying genetic predisposition who subject themselves to adverse en,environmental infl uences. The number of genes involved is unknown, as is the extent to w hich each contributes to final blood pressure and the severity of the disease. 2. In the past, studies of potential candidate genes have bee n performed by association (case-control) analysis of unrelated indivi duals or linkage (pedigree or sibpair) analysis of families. These stu dies have resulted in several positive findings but, as one may expect , also an enormous number of negative results. 3. In order to uncover the major genetic loci for essential hypertension, it is proposed that scanning the genome systematically in 100-200 affected sibships shoul d prove successful, 4. This involves genotyping sets of hypertensive s ibships to determine their complement of several hundred microsatellit e polymorphisms, Those that are highly informative, by having a high h eterozygosity, are most suitable. Also, the markers need to be spaced sufficiently evenly across the genome so as to ensure adequate coverag e. 5. Tests are performed to determine increased segregation of allele s of each marker with hypertension. The analytical tools involve speci alized statistical programs that can detect such differences. Non-para metric multipoint analysis is an appropriate approach. 6. In this way, loci for essential hypertension are beginning to emerge.