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M Pravenec

Publications and source records attributed to M Pravenec.

At least 73 records · Page 4Linked to original sources
PubMed1996

Use of AFLP markers for gene mapping and QTL detection in the rat.

The AFLP technique is a new DNA marker technology based on the selective amplification of restriction fragments. Multiple polymorphic markers are simultaneously produced and can be tested in one PCR. No prior information on genomic DNA sequences is needed. In the current study, we contribute 18 AFLP markers to the linkage map of the rat. Seven AFLP markers were assigned to specific chromosomes by analysis of a (BN x ACI)F1 x ACI backcross progeny. Another 11 AFLP markers were mapped by using a panel of the H x B/B x H recombinant inbred (RI) strains. Genotypes of these AFLP markers were also tested for correlations with some blood pressure phenotypes in the RI strains. Suggestive correlation was found between the mean arterial pressure and two closely linked AFLP markers located on chromosome 20. The current study illustrates the value of AFLP markers for the construction of linkage maps and the detection of quantitative trait loci.

Animals↗
PubMed1996

Quantitative trait loci influencing cholesterol and phospholipid phenotypes map to chromosomes that contain genes regulating blood pressure in the spontaneously hypertensive rat.

The frequent coincidence of hypertension and dyslipidemia suggests that related genetic factors might underlie these common risk factors for cardiovascular disease. To investigate whether quantitative trait loci (QTLs) regulating lipid levels map to chromosomes known to contain genes regulating blood pressure, we used a genome scanning approach to map QTLs influencing cholesterol and phospholipid phenotypes in a large set of recombinant inbred strains and in congenic strains derived from the spontaneously hypertensive rat and normotensive Brown-Norway (BN.Lx) rat fed normal and high cholesterol diets. QTLs regulating lipid phenotypes were mapped by scanning the genome with 534 genetic markers. A significant relationship (P < 0.00006) was found between basal HDL2 cholesterol levels and the D19Mit2 marker on chromosome 19. Analysis of congenic strains of spontaneously hypertensive rat indicated that QTLs regulating postdietary lipid phenotypes exist also on chromosomes 8 and 20. Previous studies in the recombinant inbred and congenic strains have demonstrated the presence of blood pressure regulatory genes in corresponding segments of chromosomes 8, 19, and 20. These findings provide support for the hypothesis that blood pressure and certain lipid subfractions can be modulated by linked genes or perhaps even the same genes.

Animals↗
PubMed1996

Effects of renin gene transfer on blood pressure and renin gene expression in a congenic strain of Dahl salt-resistant rats.

To investigate whether a BP-regulatory locus exists in the vicinity of the renin locus on rat chromosome 13, we transferred this chromosome segment from the Dahl salt-sensitive (S) rat onto the genetic background of the Dahl salt-resistant (R) rat. In congenic Dahl R rats carrying the S renin gene and fed an 8% salt diet, systolic BP was significantly lower than in progenitor Dahl R rats: 127 +/- 1 mmHg versus 138 +/- 4 mmHg, respectively (P < 0.05). Moreover, the decreased BP in the congenic Dahl R strain was associated with decreased kidney renin mRNA and decreased plasma renin concentration. These findings demonstrate that the Dahl S strain carries alleles in or near the renin locus that confer lower plasma renin concentration and lower BP than the corresponding alleles in the Dahl R strain, at least when studied on the genetic background of the Dahl R rat and in the environment of a high salt diet. The occurrence of coincident reductions in kidney renin mRNA, plasma renin concentration, and BP after interstrain transfer of naturally occurring renin gene variants strongly suggests that genetically determined variation in renin gene expression can affect BP.

Alleles↗
PubMed1996

A genetic linkage map of the rat derived from recombinant inbred strains.

We have constructed a genetic linkage map in the rat by analyzing the strain distribution patterns of 500 genetic markers in a large set of recombinant inbred strains derived from the spontaneously hypertensive rat and the Brown-Norway rat (HXB and BXH recombinant inbred strains). 454 of the markers could be assigned to specific chromosomes, and the amount of genome covered by the mapped markers was estimated to be 1151 centimorgans. By including a variety of morphologic, biochemical, immunogenetic, and molecular markers, the current map integrates and extends existing linkage data and should facilitate rat gene mapping and genetic studies of hypertension and other complex phenotypes of interest in the HXB and BXH recombinant inbred strains.

Animals↗
PubMed1996

HSP27 locus cosegregates with left ventricular mass independently of blood pressure.

Left ventricular hypertrophy remains a significant clinical problem and a predictor of fatal outcome in hypertension. Blood pressure per se and environmental modifiers including stress affect cardiac mass. Heat shock proteins are involved in the stress response as well as in the regulation of cardiac growth and cytoprotection. The present study evaluates heat shock protein 27 as a locus marker or candidate gene of cardiac hypertrophy in hypertension. The spontaneously hypertensive rat allele of heat shock protein 27 was associated with about a 6% increase in relative left ventricular weight (P = .0112) in 30 recombinant inbred strains from crosses of Brown Norway and spontaneously hypertensive rats. In 336 F2 crosses of spontaneously hypertensive and Wistar-Kyoto rats, the hypertensive allele was dominant and cosegregated with a similar 6% increase in the ratio of left ventricular weight to body weight (P = .0058) in rats fed a normal salt diet, but its contribution to left ventricular weight decreased in rats kept on a high salt diet. The contribution of the heat shock protein 27 allele was independent of blood pressure. We suggest that heat shock protein 27 represents a candidate gene/locus marker of cardiac hypertrophy in hypertension.

Alleles↗
PubMed1996

Recombinant inbred and congenic strains for mapping of genes that are responsible for spontaneous hypertension and other risk factors of cardiovascular disease.

The spontaneously hypertensive rat (SHR) is the most widely used animal model of human essential hypertension. In the SHR strain, as in humans, the high blood pressure is determined multifactorially. Analysis of genetically segregating populations, derived from SHR and normotensive inbred strains, enabled localization of quantitative trait loci (QTLs) responsible for blood pressure regulation on several rat chromosomes. Analysis of specialized strains, congenic and recombinant inbred (RI) strains, helped to analyze some of these mapping results in detail: (1) analysis of congenic strains provided definitive evidence for the presence of blood pressure regulatory genes on chromosomes 8 and 13 and will enable mapping of responsible genes to limited segments of differential chromosomes, (2) the RI strains were shown to be especially useful for genome scanning studies of complex traits and for correlation analysis of blood pressure and other risk factors of cardiovascular disease such as cardiac hypertrophy, dyslipidemia, and insulin resistance.

Animals↗
PubMed1996

Recombinant inbred and congenic strains of the rat for genetic analysis of limb morphogenesis.

Recombinant inbred (RI) and congenic strains carrying the polydactyly-luxate syndrome (PLS) provide an experimental model for the analysis of polygenic control of limb development. PLS is determined by a major gene Lx whose phenotypic expression is strongly influenced by the genetic background upon which it operates. The morphometric analysis of the skeleton of front and hind legs has been carried out. The morphotypes of PLS in RI strains exhibit a continuous variability and transgressive variation compared to BN.Lx and SHR.Lx morphotypes, which strongly indicates the polygenic effects on PLS manifestation. Quantitative trait loci (QTL) were searched for through correlation of genetic markers and morphometric traits. The association analysis revealed statistically significant correlations (P < 0.0003) of morphometric traits with two markers on chromosome 4 (Il6 and A2m) associated with the number of front feet and hind feet phalanges, respectively, one marker on chromosome 7 (D7Mit17) associated with the tibia length, and the somatostatin gene on chromosome 11 associated with the number of front feet phalanges. In addition, suggestive associations of morphometric traits with markers on further nine chromosomes have been found (correlation coefficients ranging from 0.5 to 0.6). The verification of all these findings is in progress by means of double congenic strains which, in addition to the Lx gene, carry differential chromosome segments with putative modifiers.

Animals↗
PubMed1995

Mapping and sequence analysis of the gene encoding the beta subunit of the epithelial sodium channel in experimental models of hypertension.

OBJECTIVE: To investigate whether mutations in the beta subunit of the epithelial sodium channel (Scnn1b) contribute to the pathogenesis of hypertension in the spontaneously hypertensive rat (SHR) and the Dahl salt-sensitive rat. DESIGN: We determined the chromosome location of the rat Scnn1b gene, tested for cosegregation with blood pressure, and sequenced near full-length Scnn1b complementary DNAs (cDNAs) from SHR and Dahl salt-sensitive rats. METHODS: Chromosome mapping was performed by somatic cell hybrid analysis and by linkage analysis in recombinant inbred strains derived from SHR and Brown-Norway rats. Cosegregation analysis was performed by testing for correlations between blood pressure and Scnn1b genotypes in these strains. DNA sequencing was performed on cDNAs prepared from reverse-transcribed messenger RNA derived from rat kidney. RESULTS: The Scnn1b gene was closely linked to the Sa gene on rat chromosome 1. Blood pressure correlated significantly with Scnn1b gene in the recombinant inbred strains. Analysis of near full-length Scnn1b cDNAs from SHR and Dahl rats failed to reveal any coding sequence mutations that could affect the predicted amino acid sequence of the Scnn1b protein. CONCLUSION: The Scnn1b gene maps near the Sa gene in a region of rat chromosome 1 involved in the inherited control of blood pressure. If disordered activity of the epithelial cell sodium channel contributes to the pathogenesis of hypertension in the SHR or Dahl models, it must stem from genetic lesions in sequences that regulate Scnn1b function or in sequences important to the structure or function of the other sodium channel subunits.

Animals↗
PubMed1995

Mapping of quantitative trait loci for blood pressure and cardiac mass in the rat by genome scanning of recombinant inbred strains.

In the HXB and BXH recombinant inbred strains derived from the spontaneously hypertensive rat and the normotensive Brown Norway rat, we determined the strain distribution patterns of 500 genetic markers to scan the rodent genome for quantitative trait loci regulating cardiac mass and blood pressure. The markers spanned approximately 1,139 cM of the genome and were tested for correlations with left ventricular mass adjusted for body weight, and with systolic, diastolic, and mean arterial pressures. The marker for the dopamine 1A receptor (Drd1a) on chromosome 17 showed the strongest correlation with left ventricular heart weight (P = .00038, r = -0.59) and the relationship to heart weight was independent of blood pressure. The markers showing the strongest correlations with systolic, diastolic, and mean arterial pressure were D19Mit7 on chromosome 19 (P = .0012, r = .55), D2N35 on chromosome 2 (P = .0008, r = .56), and Il6 on chromosome 4 (P = .0018, r = .53), respectively. These studies demonstrate that the HXB and BXH strains can be effectively used for genome scanning studies of complex traits and have revealed several chromosome regions that may be involved in the genetic control of blood pressure and cardiac mass in the rat.

Animals↗
PubMed1995

Chromosome 8 congenic strains: tools for genetic analysis of limb malformation, plasma triglycerides, and blood pressure in the rat.

Congenic strains with the polydactyly-luxate syndrome (PLS), the BN.lx and Lew.lx, were originally derived to study the expression and mode of inheritance of the lx mutant gene on rat chromosome 8. The BN.lx PLS congenic strain together with the spontaneously hypertensive SHR strain served as progenitors for the production of the HXB/BXH recombinant inbred (RI) strains. One of the RI strains, the BXH11, carrying PLS was used for the transfer of PLS determining lx allele onto the SHR strain genetic background. Using PCR analysis, differential segments of chromosome 8 of BN.lx and SHR.lx congenic strains were described and shown to carry also genes associated with blood pressure and plasma triglyceride regulation. Possible experimental exploitation of chromosome 8 congenic strains in these respects is thus discussed.

Animals↗
PubMed1994

Biochemical genetics of methylglyoxal dehydrogenases in the laboratory rat (Rattus norvegicus).

A genetic locus controlling the electrophoretic mobility of a methylglyoxal dehydrogenase (EC 1.2.1.23) in the rat is described. The locus, designated Mgd1, is expressed in liver and kidney. Inbred rat strains have fixed either allele Mgd1a or allele Mgd1b. Codominant expression is observed in heterozygotes, providing evidence for a tetrameric enzyme structure. Backcross progenies showed the expected 1:1 segregation ratio, and there is evidence that Mgd1 is linked to Pep3 and Fh1 on chromosome 13. There is also evidence for two additional methylglyoxal dehydrogenases: Mgd2, present in liver and kidney, and Mgd3, present only in heart.

Aldehyde Oxidoreductases↗
PubMed1994

Use of recombinant inbred strains for evaluation of intermediate phenotypes in spontaneous hypertension.

1. The HXB/BXH recombinant inbred (RI) strains, derived from the spontaneously hypertensive rat (SHR) and the normotensive Brown Norway (BN.1x) rat, represent a very useful system for gene mapping and for genetic analysis of certain model diseases, such as spontaneous hypertension. 2. These RI strains were genotyped in multiple genetic polymorphisms and characterized in blood pressure and some intermediate phenotypes. 3. The analysis of RI strains has revealed that (i) a gene in the vicinity of the major histocompatibility complex (RT1) on chromosome 20, a kallikrein-related gene on chromosome 4 and the renin gene on chromosome 13 were significantly associated with blood pressure, and (ii) Na+ leak in red blood cells correlated with blood pressure whereas relative heart and kidney weights as well as platelet aggregation did not.

Animals↗
PubMed1994

Genes of stress in experimental hypertension.

1. A significant portion of blood pressure variance is modified by the environment. 2. The present report summarizes evidence that: (i) the environmental response is genetically determined; (ii) various stressors can evoke a differential response in hypertensive animals and constitute its intermediate phenotypes; (iii) the response to heat stress can be assigned to a single 'thermosensitivity' locus; (iv) candidate genes of susceptibility to environmental stresses are member(s) of the heat stress gene (HSP) gene families; (v) a restriction fragment length polymorphism of hsp70 and a single base mutation in the 3'-untranslated region of hsp27 are associated with hypertension in recombinant inbred strains. 3. In conclusion, HSP gene variants may be causative in susceptibility to hypertension.

Animals↗
PubMed1994

Genetic contamination of Dahl SS/Jr rats. Impact on studies of salt-sensitive hypertension.

The Dahl salt-sensitive rat (SS/Jr) is a widely used animal model of salt-sensitive hypertension. SS/Jr rats are believed to be highly inbred and uniformly sensitive to the hypertensinogenic effects of sodium chloride, but we have recently observed that SS/Jr rats from Harlan Sprague Dawley, Inc, exhibit considerable variability in their blood pressure response to supplemental dietary salt. To test the possibility that commercially available SS/Jr rats are genetically contaminated and therefore no longer fully inbred, we performed molecular genetic studies and blood pressure measurements in several groups of SS/Jr rats purchased from Harlan Sprague Dawley. We found molecular evidence of heterozygosity and/or atypical allelic variants involving loci on at least five different chromosomes. Many of the rats also failed to exhibit a salt-sensitive blood pressure phenotype. We conclude that SS/Jr rats being sold by the only commercial vendor of Dahl rats in the United States are genetically contaminated and resistant to the hypertensinogenic effects of salt. These findings raise serious questions about the interpretation of research conducted with SS/Jr rats obtained from Harlan Sprague Dawley.

Animals↗
PubMed1994

Genetic mapping of two new blood pressure quantitative trait loci in the rat by genotyping endothelin system genes.

The endothelin system, consisting of a series of potent vasoconstrictor peptides and their receptors, is potentially important in the control of blood pressure. We found that the gene coding for endothelin-2 (ET2), also known as vasoctive intestine peptide, cosegregated strongly with systolic blood pressure in a F2 population [F2(S x LEW)] derived from a cross of the Dahl salt-sensitive (S) rat and the Lewis (LEW/NCrlBR) (LEW) rat. The ET2 locus was assigned to rat chromosome 5. The testis-specific histone (HITH) locus also strongly cosegregated with blood pressure in the F2(S x LEW) population and was assigned to rat chromosome 17. Genetic maps of the regions containing the quantitative trait loci (QTL) for blood pressure on chromosomes 5 and 17 were constructed and the QTL were localized using the MAPMAKER/QTL program. The rat genes for endothelin-1, endothelin-3, and endothelin receptor A did not cosegregate with blood pressure in several F2 populations tested and were assigned to rat chromosomes 17, 3, and 19, respectively. Endothelin receptor B cosegregated weakly with blood pressure and was provisionally assigned to rat chromosome 15. We conclude that, in the rat, one new blood pressure QTL is located on chromosome 5 marked by the ET2 locus and another new QTL is located on chromosome 17 near the HITH locus.

Animals↗