RGD Reference Report - Genetic dissection of region around the Sa gene on rat chromosome 1: evidence for multiple loci affecting blood pressure. - Rat Genome Database

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Genetic dissection of region around the Sa gene on rat chromosome 1: evidence for multiple loci affecting blood pressure.

Authors: Frantz, S  Clemitson, JR  Bihoreau, MT  Gauguier, D  Samani, NJ 
Citation: Frantz S, etal., Hypertension 2001 Aug;38(2):216-21.
RGD ID: 70855
Pubmed: PMID:11509479   (View Abstract at PubMed)

A region with a major effect on blood pressure (BP) is located on rat chromosome 1 in the vicinity of the Sa gene, a candidate gene for BP regulation. Previously, we observed a single linkage peak for BP in this region in second filial generation rats derived from a cross of the spontaneously hypertensive rat (SHR) with the Wistar-Kyoto rat (WKY), and we have reported the isolation of the region containing the BP effect in reciprocal congenic strains (WKY.SHR-Sa) and (SHR.WKY-Sa) derived from these animals. Here, we report the further genetic dissection of this region. Two congenic substrains each were derived from WKY.SHR-Sa (WISA1 and WISA2) and SHR.WKY-Sa (SISA1 and SISA2) by backcrossing to WKY and SHR, respectively. Although there was some overlap of the introgressed regions retained in the various substrains, the segments in WISA1 and SISA1 did not overlap. Furthermore, although the Sa allele in WISA1, WISA2, and SISA2 remained donor in origin, recombination in SISA1 reverted it back to the recipient (SHR) allele. Surprisingly, all 4 substrains demonstrated a highly significant BP difference compared with that of their respective parental strain, which was of a magnitude similar to those seen in the original congenic strains. The findings strongly indicate that there are at least 2 quantitative trait loci (QTLs) affecting BP in this region of rat chromosome 1. Furthermore, the BP effect seen in SISA1 indicates that at least a proportion of the BP effect of this region of rat chromosome 1 cannot be due to the Sa gene. SISA1 contains an introgressed segment of <3 cM, and this will facilitate the physical mapping of the BP QTL(s) located within it and the identification of the susceptibility-conferring genes. Our observations serve to illustrate the complexity of QTL dissection and the care needed to interpret findings from congenic studies.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  IDA 70855; 70855 RGD 
hypertension MODEL: spontaneousIAGP 70855compared to WKY/NCruk strainRGD 
hypertension MODEL: controlIAGP 70855compared to SHR/NCruk strainRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
decreased mean systemic arterial blood pressure  IAGP 70855compared to SHR/NCruk strainRGD 
decreased systemic arterial diastolic blood pressure  IAGP 70855; 70855; 70855compared to SHR/NCruk strainRGD 
decreased systemic arterial systolic blood pressure  IAGP 70855; 70855; 70855compared to SHR/NCruk strainRGD 
increased mean systemic arterial blood pressure  IAGP 70855compared to WKY/NCruk strainRGD 
increased systemic arterial blood pressure  IAGP 70855; 70855 RGD 
increased systemic arterial diastolic blood pressure  IAGP 70855; 70855; 70855compared to WKY/NCruk strainRGD 
increased systemic arterial systolic blood pressure  IAGP 70855; 70855; 70855compared to WKY/NCruk strainRGD 

Objects Annotated

QTLs
Bp77  (Blood pressure QTL 77)
Bp78  (Blood pressure QTL 78)


Additional Information