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Dahl (S x R) congenic strain analysis confirms and defines a chromosome 5 female-specific blood pressure quantitative trait locus to <7 Mbp.

Authors: Herrera, VL  Pasion, KA  Moran, AM  Ruiz-Opazo, N 
Citation: Herrera VL, etal., PLoS One. 2012;7(7):e42214. doi: 10.1371/journal.pone.0042214. Epub 2012 Jul 30.
Pubmed: (View Article at PubMed) PMID:22860086
DOI: Full-text: DOI:10.1371/journal.pone.0042214

The detection of multiple sex-specific blood pressure (BP) quantitative trait loci (QTLs) in independent total genome analyses of F2 (Dahl S x R)-intercross male and female rat cohorts confirms clinical observations of sex-specific disease cause and response to treatment among hypertensive patients, and mandate the identification of sex-specific hypertension genes/mechanisms. We developed and studied two congenic strains, S.R5A and S.R5B introgressing Dahl R-chromosome 5 segments into Dahl S chromosome 5 region spanning putative BP-f1 and BP-f2 QTLs. Radiotelemetric non-stressed 24-hour BP analysis at four weeks post-high salt diet (8% NaCl) challenge, identified only S.R5B congenic rats with lower SBP (-26.5 mmHg, P = 0.002), DBP (-23.7 mmHg, P = 0.004) and MAP (-25.1 mmHg, P = 0.002) compared with Dahl S female controls at four months of age confirming BP-f1 but not BP-f2 QTL on rat chromosome 5. The S.R5B congenic segment did not affect pulse pressure and relative heart weight indicating that the gene underlying BP-f1 does not influence arterial stiffness and cardiac hypertrophy. The results of our congenic analysis narrowed BP-f1 to chromosome 5 coordinates 134.9-141.5 Mbp setting up the basis for further fine mapping of BP-f1 and eventual identification of the specific gene variant accounting for BP-f1 effect on blood pressure.

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CRRD Object Information
CRRD ID: 7364997
Created: 2013-10-15
Species: All species
Last Modified: 2013-10-15
Status: ACTIVE



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