Mapping genes controlling hematocrit in the spontaneously hypertensive rat

Abstract

The genes that determine the baseline hematocrit level in humans and experimental animals are unknown. The spontaneously hypertensive rat (SHR), the most widely used animal model of human essential hypertension, exhibits an increased hematocrit when compared with the normotensive Brown Norway (BN-Lx) strain (0.54 +/- 0.02 vs. 0.44 +/- 0.02, p < 0.01). Distribution of hematocrit values among recombinant inbred (RI) strains derived from SHR and BN-Lx progenitors was continuous, which suggests a polygenic mode of inheritance. The narrow heritability of the hematocrit was estimated to be 0.32. The Eno2 marker on Chromosome (Chr) 4 showed the strongest association (p < 0.0001) with the observed variability of hematocrit among RI strains. The erythropoietin (Epo) gene, originally reported to be syntenic with Eno2, has been mapped to Chr 12, thus excluding it as a potential candidate gene for the increased hematocrit in the SHR. The current linkage data extend homologies between rat, mouse, and human chromosomes.

Evidence for a gene influencing haematocrit on chromosome 6q23-24: genomewide scan in the Framingham Heart Study

“…A genome scan to map genes controlling HCT in the spontaneously hypertensive rat indicated a significant association between a marker on chromosome 4 and the observed variability of HCT. 17 No association was found between HCT and erythropoietin, which was mapped to chromosome 12 in rat. 17 So far, no linkage analysis of HCT in humans has been reported.…”

“…17 No association was found between HCT and erythropoietin, which was mapped to chromosome 12 in rat. 17 So far, no linkage analysis of HCT in humans has been reported. We thus report one of the first linkage studies of HCT in the Framingham Heart Study, with the goal of identifying chromosomal regions that may contain quantitative trait loci (QTL) involved in controlling HCT.…”

Impact of cadmium on the level of hepatic metallothioneins, essential elements, and selected enzymes in the experimental rat model

“…In this study, Spontaneously hypertensive rats (SHR) and Brown Norway (BN) (Pravenec et al 1996(Pravenec et al , 1997Pravenec and Kurtz 2010) were chosen as genetically far distant models. For comparison, outbred strain Long Evans (LE) with less than 1% relation in generation was used.…”

A dual-color FISH gene map of the proximal region of rat Chromosome 4 and comparative analysis in human and mouse

“…However, their reasoning was based on partially incorrect assumptions, because, when they wrote their paper, the Epo gene, which is situated in HSA7q22, had been erroneously assigned to RNO4. This gene has now been reassigned to RNO12 independently by two different groups using two different mapping methods Pravenec et al 1997). Actually, this change makes the idea put forward by Trezise et al (1992) even more attractive, because, even though Epo does in fact map to MMU5, it maps far away from the genes with homologs on RNO4.…”