Affiliation:
1. From the Laboratory for Molecular Medicine and Department of Nephrology and Hypertension (C.Y., M.S., Y.Y.), Faculty of Health Sciences, Ben-Gurion University, Barzilai Medical Center Campus, Ashkelon, Israel, and Benjamin Franklin Hospital (R.K., H.Z., D.G.), Free University of Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Abstract
Abstract
—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 F
2
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 F
2
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 F
2
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 F
2
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Reference9 articles.
1. Genetic basis of salt-susceptibility in the Sabra rat model of hypertension
2. Development, genotype and phenotype of a new colony of the Sabra hypertension prone (SBH/y) and resistant (SBN/y) rat model of salt sensitivity and resistance
3. Lincoln S Daly M Lander E. Constructing genetic maps with MAPMAKER/EXP 3.0. 3rd ed. Cambridge Mass: Whitehead Institute Technical Report; 1992.
4. Lincoln S Daly M Lander E. Mapping genes controlling quantitative traits with MAPMAKER/QTL 1.1. 2nd ed. Cambridge Mass: Whitehead Institute Technical Report; 1992.
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