RGD Reference Report - Role of chromosome X in the Sabra rat model of salt-sensitive hypertension. - Rat Genome Database

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Role of chromosome X in the Sabra rat model of salt-sensitive hypertension.

Authors: Yagil, C  Sapojnikov, M  Kreutz, R  Zurcher, H  Ganten, D  Yagil, Y 
Citation: Yagil C, etal., Hypertension 1999 Jan;33(1 Pt 2):261-5.
RGD ID: 69713
Web Url: http://www.hypertensionaha.org/cgi/content/full/33/1/261
Pubmed: PMID:9931114   (View Abstract at PubMed)

We carried out a total genome screen in the Sabra rat model of hypertension to detect salt-susceptibility genes. We previously reported in male animals the presence of 2 major quantitative trait loci (QTLs) on chromosome 1 that together accounted for most of the difference in the blood pressure (BP) response to salt loading between Sabra hypertension-prone rats (SBH/y) and Sabra hypertension-resistant rats (SBN/y). In females, we reported on 2 major QTLs on chromosomes 1 and 17 that together accounted for only two thirds of the difference in the BP response between the strains. On the basis of phenotypic patterns of inheritance in reciprocal F2 crosses, we proposed a role of the X chromosome. We therefore continued the search for the missing QTL in females that would account for the remaining difference in the BP response between the 2 strains using newly developed microsatellite markers and focusing on chromosome X. We screened an F2 cross, consisting of 371 females and 336 males, using 19 polymorphic chromosome X microsatellite markers. We analyzed the averages of BP by genotype using ANOVA and the individual data using MAPMAKER/QTL. In female F2 progeny, we identified a segment on chromosome X that spans over 33.4 cM and shows significant cosegregation (P<0.001) of 14 microsatellite markers (demarcated by DXRat4 and DXMgh10) with systolic BP after salt loading. This segment has 2 apparent peaks at DXRat4 and DXRat13, with a BP effect of 14 mm Hg for each. Multipoint linkage analysis with a free model detected 3 peaks (logarithm of the odds ratio [LOD] score >4.3) within the same chromosomal segment: One between DXMgh9 and DXMit4 (LOD 4.9; 6.1% of variance), a second between DXMgh12 and DXRat8 (LOD 5.2; 7.2% of variance), and a third between DXRat2 and DXRat4 (LOD 5.8; 7.5% of variance). On the basis of these findings and until congenic strains become available, our working assumption is that within chromosome X, 1 to 3 genetic loci contribute importantly to the BP response of female Sabra rats to salt. In male F2 progeny, we detected no significant cosegregation of any region on chromosome X with the BP response to salt loading. We conclude that in the female rat, salt susceptibility is mediated by 3 to 5 gene loci on chromosomes 1, 17, and X, whereas in the male rat, the X chromosome does not affect the BP response to salt.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  IDA 69713; 69713; 69713 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
increased systemic arterial blood pressure  QTM 69713; 69713; 69713 RGD 
Objects Annotated

QTLs
Bp56  (Blood pressure QTL 56)
Bp64  (Blood pressure QTL 64)
Bp65  (Blood pressure QTL 65)

Strains
SBH/Ygl  (Sabra hypertension prone)
SBN/Ygl  (Sabra hypertension resistant)

Objects referenced in this article
Strain SBH Sabra hypertensive Rattus norvegicus
Strain SBN null Rattus norvegicus

Additional Information