| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
To investigate the genetic control of hypertension, we performed a quantitative trait locus analysis on male mice from a reciprocal backcross between the salt-sensitive C57BL/6J and the normotensive A/J inbred mouse slrains after they were provided with water containing 1% salt for 2 weeks. Genome-wide scans performed on these mice and analyzed with a combination of conventional markerbased regressions and a novel simultaneous search for pairs revealed six significant quantitative trait loci associated with salt-induced blood pressure, two of which were interacting loci. These six loci, named Bpq1-6 for blood pressure quantitative trait loci, mapped to D1Mit334, D1Mit14, D4Mit164, D5Mit31, D6Mit15, and D15Mit13, Furthermore, five of these six loci were concordant with hypertension loci hi rats, and four were concordant with hypertension loci in humans, suggesting that quantitative trait loci mapping in model organisms can be used to guide the search for human blood pressure genes.
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tter understand the genetic basis of essential hypertension, we conducted a QTL analysis of a population of 207 (BALB/cJ x CBA/CaJ) F(2) male mice to identity genomic regions that regulate blood pressure, heart rate, and heart weight. We identified two loci, Bpq6 (blood pressure quantitative locus 6) on chromosome 15 (Chr 15 ; peak, 16 cM ; 95% confidence interval, 0-25 cM) and Bpq7 on Chr 7 (peak, 42 cM ; 95% confidence interval, 35-50 cM) that were significantly associated with blood pressure. We also identified two loci, Hrql (heart rate quantitative locus 1) and Hrq2, on D2Mt304 (peak, 72 cM ; 95% confidence interval 60-80 cM) and D15MM84 (peak, 25 cM ; 95% confidence interval 20-35 cM), respectively, that were sigruficantiy associated with heart rate. A significant gene-gene interaction for heart rate was found between Hrql and DlAfltlO (peak, 57 cM ; 95% confidence interval, 45-75 CM) ; the latter QTL was named Hrq3. fae identified a significant locus for heart weight, Jfwgl (heart weight quantitative locus 1), at D14Mit67 (peak, 38cM ; 95% confidence interval, 20-43 cM). Identification of the genes for these QTL should lead to a better understanding of the causes of essential hypertension. Less
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