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Genomics of salt-induced hypertension
Researchers identify chromosome regions of interest in mice, humans, and rats
By Barbra Rodriguez

Researchers have taken the first steps toward identifying genes that make some mice susceptible to hypertension. Using genome scans and computational tools, the investigators located regions of mouse chromosomes likely to contain risk factors for the salt-sensitive form of the condition. The study identified corresponding regions of the human and the rat genomes, supporting the notion that a fundamental similarity exists across species and that pinpointing genes in rodents could lead researchers to blood pressure genes in humans.

Mouse having its blood pressure taken at the Jackson Laboratory.

Researchers from the Jackson Laboratory in Bar Harbor, Maine, and the University of Tsukuba, Japan, bred a salt-insensitive strain of mice to a strain whose blood pressure climbs from drinking salty water. They then studied 250 male offspring given access to water spiked with 1 percent salt for two weeks. (The effects of salt are easier to study in male mice because their blood pressure climbs higher than that of females when exposed to dietary salt.)

The animals' blood pressure was checked after the two weeks using a miniature 'cuff' slipped around their tails. In addition, the researchers studied DNA obtained from the 92 male offspring with the highest and lowest blood pressure readings. The animals' genomes were tagged with 131 markers at regular intervals along the chromosomes. Once the investigators knew which chromosomes likely held the genes of interest, they repeated this process for all 250 animals with a larger panel of markers. The findings appeared in a recent issue of Genomics.

The researchers identified two regions containing genes that influence salt-sensitive hypertension in mice on chromosome 1, and one region each on chromosomes 4, 5, 6, and 15. Because some of the genes in the candidate regions might work together to promote the condition, the researchers looked at this possibility. The regions identified on chromosome 6 and chromosome 15 in mice appear to interact to promote hypertension, and to have more influence on hypertension than all other blood pressure-related regions identified. Moreover, these two regions and two others the researchers identified had evolutionarily conserved counterparts in humans suspected of influencing hypertension.

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Sugiyama, F. et al. Concordance of murine quantitative trait loci for salt-induced hypertension with rat and human loci. Genomics 71, 70-77 (January 2001).

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