In search of hypertension genes in Dahl salt-sensitive rats

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Quantitative trait loci in Dahl ratsGenetic and crude physical mapping have yielded chromosome regions containing quantitative trait loci for blood pressure in Dahl salt-sensitive rats. So far, the molecular identities of these loci are largely unknown. Intriguing still is how these quantitative trait loci would interact with each other to achieve an overall blood pressure effect. Alleles of some loci previously identified as blood pressure quantitative trait loci in other rat strains appear to be the same between Dahl salt-sensitive and salt-resistant rats. Why do Dahl salt-resistant rats have low blood pressure whereas Dahl salt-sensitive rats develop high blood pressure?Recent findingsWith the use of congenic strains and ‘double’ congenics, these issues have begun to unravel. Certain quantitative trait loci exert major blood pressure effects (> 20 mmHg) and each of them can be dissected as a monogenic trait. Some appear to be located close to each other in the same chromosome region. Different quantitative trait loci interact epistatically to produce their combined blood pressure effects. ‘Low’ blood pressure alleles of one quantitative trait locus can compensate for the ‘high’ blood pressure alleles of other quantitative trait loci in the Dahl salt-resistant rat. By integrating fine mapping and positional cloning strategies, blood pressure quantitative trait loci are being elucidated. Work in the rat may also facilitate genetic mapping of quantitative trait loci in humans.

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