Key result
Congenic strain C8S.L1 lowered blood pressure compared to S rats, whereas C8S.L2 raised blood pressure, revealing at least two quantitative trait loci with opposite effects on chromosome 8.
The study identifies at least two quantitative trait loci with opposite effects on blood pressure on chromosome 8 in Dahl rats, highlighting the genetic complexity of hypertension.
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Reveals opposing QTLs on rat chromosome 8; hypothesis-generating for human hypertension genetics and should not change practice.
OBJECTIVE: Our previous linkage analyses showed that there was likely a quantitative trait locus (QTL) for blood pressure (BP) on chromosome 8 (Chr 8) in the strain comparison between the Dahl salt-sensitive (S) and the Lewis (LEW) rats. The current work is to delineate the chromosome interval harboring this QTL by using congenic strains with different chromosome substitutions. METHODS: Two congenic strains were produced by replacing different segments of the S rats with the homologous segments of the LEW rats. A genome-wide marker screening was utilized to accelerate this process. The two strains generated are designated as C8S.L1 and C8S.L2, respectively. BPs of the rats were measured by telemetry. RESULTS: C8S.L1 showed a BP lower than that of S rats. In contrast, C8S.L2 did not have chromosome overlaps with C8S.L1, but unexpectedly, exhibited a BP-raising effect, higher than that of S rats. CONCLUSION: There are at least two QTLs present in a section of Chr 8 that possess opposite BP effects. The current congenic work reveals not only the presence of QTLs, but the complexity of QTLs on BP. The novel congenic strain with hypertension more severe than S provides a new model for studies in elucidating physiological mechanisms controlling BP.
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Ariyarajah et al. (2004) studied Hypertension. Congenic strains C8S.L1 and C8S.L2 vs. Dahl salt-sensitive (S) rats was evaluated on Blood pressure measured by telemetry. Congenic strain C8S.L1 lowered blood pressure compared to S rats, whereas C8S.L2 raised blood pressure, revealing at least two quantitative trait loci with opposite effects on chromosome 8.
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