RGD Reference Report - Applicability of a "speed" congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2. - Rat Genome Database

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Applicability of a "speed" congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2.

Authors: Jeffs, B  Negrin, CD  Graham, D  Clark, JS  Anderson, NH  Gauguier, D  Dominiczak, AF 
Citation: Jeffs B, etal., Hypertension 2000 Jan;35(1 Pt 2):179-87.
RGD ID: 68910
Pubmed: PMID:10642295   (View Abstract at PubMed)

The identification of any quantitative trait locus (QTL) via a genome scan is only the first step toward the ultimate goal of gene identification. The next step is the production of congenic strains by which the existence of a QTL may be verified and the implicated chromosomal region be reduced to a size applicable to positional cloning of the causal gene. We used a speed congenic breeding protocol previously verified in mice for 2 blood pressure QTLs on rat chromosome 2. Four congenic strains were produced through introgression of various segments of chromosome 2 from Wistar-Kyoto rats from Glasgow colonies [WKY((Gla)) rats] into the recipient stroke-prone spontaneously hypertensive rats from Glasgow colonies [SHRSP((Gla))], and vice versa. The number of backcross generations required for each strain to achieve complete homozygosity at 83 background genetic markers in a "best" male varied between 3 and 4. Transfer of the region of rat chromosome 2 containing both QTLs from WKY((Gla)) into an SHRSP((Gla)) genetic background lowered both baseline and salt-loaded systolic blood pressure by approximately 20 and approximately 40 mm Hg in male congenic rats compared with the SHRSP parental strain (F=53.4, P<0.005; F=28.0, P< 0.0005, respectively). In contrast, control animals for stowaway heterozygosity presented no deviation from the blood pressure values recorded for the SHRSP((Gla)), indicating that if such heterozygosity exists, its effect on blood pressure is negligible. A reciprocal strategy in which 1 or both QTLs on rat chromosome 2 were transferred from SHRSP((Gla)) into a WKY((Gla)) genetic background resulted in statistically significant but smaller blood pressure increases for 1 of these QTLs. These results confirm the existence of blood pressure QTLs on rat chromosome 2 and demonstrate the applicability of a speed congenic strategy in the rat and emphasize the important role of the genetic background.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  IDA 68910; 68910 RGD 
hypertension  IAGP 68910 RGD 
hypertension sexual_dimorphism IAGP 68910 RGD 
hypertension susceptibilityIAGP 68910; 68910compared to control strain WKY/GcrcRGD 
hypertension sexual_dimorphism IAGP 68910compared to WKY/GcrcRGD 
hypertension MODEL: spontaneousIAGP 68910compared to control strain WKY/GcrcRGD 
hypertension MODEL: controlIAGP 68910compared to spontaneously hypertensive strain SHRSP/GcrcRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
decreased mean systemic arterial blood pressure  IAGP 68910compared to spontaneously hypertensive strain SHRSP/GcrcRGD 
decreased susceptibility to hypertension susceptibilityIAGP 68910; 68910compared to spontaneously hypertensive strain SHRSP/GcrcRGD 
decreased susceptibility to hypertension  IAGP 68910compared to spontaneously hypertensive strain SHRSP/GcrcRGD 
decreased systemic arterial blood pressure  IAGP 68910 RGD 
decreased systemic arterial diastolic blood pressure  IAGP 68910compared to spontaneously hypertensive strain SHRSP/GcrcRGD 
decreased systemic arterial systolic blood pressure susceptibilityIAGP 68910compared to spontaneously hypertensive strain SHRSP/GcrcRGD 
decreased systemic arterial systolic blood pressure  IAGP 68910compared to spontaneously hypertensive strain SHRSP/GcrcRGD 
increased heart weight  IAGP 68910 RGD 
increased mean systemic arterial blood pressure sexual_dimorphism IAGP 68910compared to WKY/GcrcRGD 
increased mean systemic arterial blood pressure disease_progressionIAGP 68910compared to control strain WKY/GcrcRGD 
increased susceptibility to hypertension susceptibilityIAGP 68910; 68910compared to control strain WKY/GcrcRGD 
increased susceptibility to hypertension sexual_dimorphism IAGP 68910 RGD 
increased susceptibility to hypertension disease_progressionIAGP 68910compared to control strain WKY/GcrcRGD 
increased systemic arterial blood pressure  IAGP 68910; 68910; 68910 RGD 
increased systemic arterial diastolic blood pressure sexual_dimorphism IAGP 68910compared to WKY/GcrcRGD 
increased systemic arterial diastolic blood pressure disease_progressionIAGP 68910compared to control strain WKY/GcrcRGD 
increased systemic arterial systolic blood pressure sexual_dimorphism IAGP 68910compared to WKY/GcrcRGD 
increased systemic arterial systolic blood pressure disease_progressionIAGP 68910compared to control strain WKY/GcrcRGD 
increased systemic arterial systolic blood pressure susceptibilityIAGP 68910compared to control strain WKY/GcrcRGD 
salt-resistant hypertension  IAGPcontrolled sodium content drinking water68910compared to spontaneously hypertensive strain SHRSP/GcrcRGD 
salt-sensitive hypertension susceptibilityIAGPcontrolled sodium content drinking water68910compared to control strain WKY/GcrcRGD 
salt-sensitive hypertension sexual_dimorphism IAGP 68910 RGD 
salt-sensitive hypertension susceptibilityIAGPcontrolled sodium content drinking water68910compared to control strain WKY/Gcrc and sexual dimorphismRGD 

Objects Annotated

QTLs
Bp132  (Blood pressure QTL 132)
Bp163  (Blood pressure QTL 163)
Cm14  (Cardiac mass QTL 14)

Strains
SHRSP.WKY-(D2Rat13-D2Mit5)/Gcrc  (NA)
SHRSP.WKY-(D2Rat13-D2Rat157)/Gcrc  (NA)
SHRSP/Gcrc  (Spontaneously hypertensive rat, stroke prone)
WKY.SHRSP-(D2Mit5-D2Mgh12)/Gcrc  (NA)
WKY.SHRSP-(Fst-Pklr)/Gcrc  (NA)
WKY/Gcrc  (Wistar-Kyoto)

Objects referenced in this article
QTL Bp13 Blood pressure QTL 13 Rattus norvegicus
QTL Bp14 Blood pressure QTL 14 Rattus norvegicus
QTL Bp6 Blood pressure QTL 6 Rattus norvegicus

Additional Information