SCANNING THE GENOME FOR ESSENTIAL HYPERTENSION LOCI

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Abstract

SUMMARY

1. Essential hypertension occurs in people with an underlying genetic predisposition who subject themselves to adverse environmental influences. The number of genes involved is unknown, as is the extent to which each contributes to final blood pressure and the severity of the disease.

2. In the past, studies of potential candidate genes have been performed by association (case-control) analysis of unrelated individuals or linkage (pedigree or sibpair) analysis of families. These studies 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 should prove successful.

4. This involves genotyping sets of hypertensive sibships to determine their complement of several hundred microsatellite polymorphisms. Those that are highly informative, by having a high heterozygosity, are most suitable. Also, the markers need to be spaced sufficiently evenly across the genome so as to ensure adequate coverage.

5. Tests are performed to determine increased segregation of alleles of each marker with hypertension. The analytical tools involve specialized statistical programs that can detect such differences. Non-parametric multipoint analysis is an appropriate approach.

6. In this way, loci for essential hypertension are beginning to emerge.

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