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

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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.
RGD ID: 7364997
Pubmed: PMID:22860086   (View Abstract at PubMed)
PMCID: PMC3408448   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0042214   (Journal Full-text)

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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Objects Annotated

QTLs
Bp359  (Blood pressure QTL 359)

Objects referenced in this article
Marker rs65785750 rs65785750 Rattus norvegicus
Marker rs105133245 rs105133245 Rattus norvegicus
Marker rs105835643 rs105835643 Rattus norvegicus
Marker rs13452155 rs13452155 Rattus norvegicus
Marker rs105127111 rs105127111 Rattus norvegicus
Marker rs106808193 rs106808193 Rattus norvegicus
Marker rs13450610 rs13450610 Rattus norvegicus
QTL Bp292 Blood pressure QTL 292 Rattus norvegicus
QTL Bp293 Blood pressure QTL 293 Rattus norvegicus
Strain SS.SR-(rs65785750-rs13452155)/Opaz null Rattus norvegicus

Additional Information