ABSTRACT
The relationship between activation of the sympathetic nervous system and cardiac hypertrophy has long been known. However, the molecular genetic basis of this association is poorly understood. Given the known role of hypothalamic norepinephrine in the activation of the sympathetic nervous system, the aim of the work was to carry out genetic mapping using Quantitative Trait Loci (QTL) analysis and determine the loci associated both with an increase in the concentration of norepinephrine in the hypothalamus and with an increase in heart mass in Inherited Stress-Induced Arterial Hypertension (ISIAH) rats simulating the stress-sensitive form of arterial hypertension. The work describes a genetic locus on chromosome 18, in which there are genes that control the development of cardiac hypertrophy associated with an increase in the concentration of norepinephrine in the hypothalamus, i.e., genes involved in enhanced sympathetic myocardial stimulation. No association of this locus with the blood pressure was found. Taking into consideration previously obtained results, it was concluded that the contribution to the development of heart hypertrophy in the ISIAH rats is controlled by different genetic loci, one of which is associated with the concentration of norepinephrine in the hypothalamus (on chromosome 18) and the other is associated with high blood pressure (on chromosome 1). Nucleotide substitutions that may be involved in the formation or absence of association with blood pressure in different rat strains are discussed.
ABSTRACT
Down-regulator associated protein, DrAp1, acts as a negative cofactor (NC2α) in a transcription repressor complex together with another subunit, down-regulator Dr1 (NC2ß). In binding to promotors and regulating the initiation of transcription of various genes, DrAp1 plays a key role in plant transition to flowering and ultimately in seed production. TaDrAp1 and TaDrAp2 genes were identified, and their expression and genetic polymorphism were studied using bioinformatics, qPCR analyses, a 40K Single nucleotide polymorphism (SNP) microarray, and Amplifluor-like SNP genotyping in cultivars of bread wheat (Triticum aestivum L.) and breeding lines developed from a cross between spelt (T. spelta L.) and bread wheat. TaDrAp1 was highly expressed under non-stressed conditions, and at flowering, TaDrAp1 expression was negatively correlated with yield capacity. TaDrAp2 showed a consistently low level of mRNA production. Drought caused changes in the expression of both TaDrAp1 and TaDrAp2 genes in opposite directions, effectively increasing expression in lower yielding cultivars. The microarray 40K SNP assay and Amplifluor-like SNP marker, revealed clear scores and allele discriminations for TaDrAp1 and TaDrAp2 and TaRht-B1 genes. Alleles of two particular homeologs, TaDrAp1-B4 and TaDrAp2-B1, co-segregated with grain yield in nine selected breeding lines. This indicated an important regulatory role for both TaDrAp1 and TaDrAp2 genes in plant growth, ontogenesis, and drought tolerance in bread and spelt wheat.
Subject(s)
Gene Expression Regulation, Plant/genetics , Phosphoproteins/genetics , Transcription Factors/genetics , Triticum/genetics , Alleles , Droughts , Genes, Plant/genetics , Phosphoproteins/metabolism , Plant Breeding/methods , Plant Development/genetics , Polymorphism, Single Nucleotide/genetics , Repressor Proteins/genetics , Repressor Proteins/metabolism , Seeds , Stress, Physiological/genetics , Transcription Factors/metabolism , Triticum/metabolismABSTRACT
BACKGROUND: The kidney mass is significantly increased in hypertensive ISIAH rats with Inherited Stress Induced Arterial Hypertension as compared with normotensive WAG rats. The QTL/microarray approach was carried out to determine the positional candidate genes in the QTL for absolute and relative kidney weight. RESULTS: Several known and predicted genes differentially expressed in ISIAH and WAG kidney were mapped to genetic loci associated with the absolute and relative kidney weight in 6-month old F2 hybrid (ISIAHxWAG) males. The knowledge-driven filtering of the list of candidates helped to suggest several positional candidate genes, which may be related to the structural and mass changes in hypertensive ISIAH kidney. CONCLUSIONS: The further experimental validation of causative genes and detection of polymorphisms will provide opportunities to advance our understanding of the underlying nature of structural and mass changes in hypertensive ISIAH kidney.
Subject(s)
Hypertension/genetics , Kidney/pathology , Quantitative Trait Loci , Animals , Blood Pressure , Gene Expression Profiling , Male , Microsatellite Repeats , Oligonucleotide Array Sequence Analysis , Organ Size , Polymorphism, Genetic , RatsABSTRACT
The genetic basis of the stress-sensitive arterial hypertension was investigated using the quantitative trait loci (QTL) approach. Two groups of F2 (inherited stress-induced arterial hypertension [ISIAH] × Wistar albino Glaxo [WAG]) hybrid males of different age (3-4 months old and 6 months old) were tested for blood pressure at rest and stressed conditions and for body composition traits. Several novel loci for the traits were determined. Some loci for blood pressure and organ weight were mapped to the same genetic region in rats of different age. The dynamic change of QTL effects in two rat groups of different age might reflect the process of stress-sensitive hypertension development.
Subject(s)
Blood Pressure/genetics , Body Composition/genetics , Hypertension/etiology , Hypertension/genetics , Age Factors , Animals , Hybridization, Genetic , Hypertension/physiopathology , Male , Organ Size/genetics , Quantitative Trait Loci , Rats , Rats, Wistar , Stress, PsychologicalABSTRACT
The genetic background of the regulatory systems of the hypothalamic-pituitary-adrenal (HPA) axis in hypertension remains unclear. The inherited stress-induced arterial hypertension (ISIAH) and Wistar Albino Glaxo (WAG) normotensive rats were bred and their F(2) progeny were used in a quantitative trait loci (QTL) analysis to identify genomic regions for plasma basal and stress-induced corticosterone levels, and for absolute and relative adrenal gland weights. The significant loci were found for stress-induced corticosterone on chromosome 9 and for adrenal weight on chromosome 6. The results may help to identify the genes controlling the trait phenotypes in the ISIAH rats characterized by the enhanced responsiveness to stressful stimulation.
