HLA gene expression is altered in whole blood and placenta from women who later developed preeclampsia
In this study, we used a non-biased microarray approach to identify dysregulated genes in maternal whole blood samples which may be associated with the development of preeclampsia. Whole blood samples were obtained at 28 wk of gestation from 5 women who later developed preeclampsia (cases) and 10 matched women with normotensive pregnancies (controls). Placenta samples were obtained from an independent cohort of 19 women with preeclampsia matched with 19 women with normotensive pregnancies. We studied gene expression profiles using Illumina microarray in blood and validated changes in gene expression in whole blood and plac...
Source: Physiological Genomics - March 17, 2017 Category: Genetics & Stem Cells Authors: Small, H. Y., Akehurst, C., Sharafetdinova, L., McBride, M. W., McClure, J. D., Robinson, S. W., Carty, D. M., Freeman, D. J., Delles, C. Tags: Research Articles Source Type: research
Nephron number, hypertension, and CKD: physiological and genetic insight from humans and animal models
The kidneys play a vital role in the excretion of waste products and the regulation of electrolytes, maintenance of acid–base balance, regulation of blood pressure, and production of several hormones. Any alteration in the structure of the nephron (basic functional unit of the kidney) can have a major impact on the kidney’s ability to work efficiently. Progressive decline in kidney function can lead to serious illness and ultimately death if not treated by dialysis or transplantation. While there have been numerous studies that implicate lower nephron numbers as being an important factor in influencing suscepti...
Source: Physiological Genomics - March 17, 2017 Category: Genetics & Stem Cells Authors: Wang, X., Garrett, M. R. Tags: Review Source Type: research
Modeling diseases in multiple mouse strains for precision medicine studies
The genetic basis of the phenotypic variability observed in patients can be studied in mice by generating disease models through genetic or chemical interventions in many genetic backgrounds where the clinical phenotypes can be assessed and used for genome-wide association studies (GWAS). This is particularly relevant for rare disorders, where patients sharing identical mutations can present with a wide variety of symptoms, but there are not enough number of patients to ensure statistical power of GWAS. Inbred strains are homozygous for each loci, and their single nucleotide polymorphisms catalogs are known and freely avai...
Source: Physiological Genomics - March 13, 2017 Category: Genetics & Stem Cells Authors: Klein, A. D. Tags: Perspectives Source Type: research
Alternative transcription of sodium/bicarbonate transporter SLC4A7 gene enhanced by single nucleotide polymorphisms
In this study, we examined rs3278 and three adjacent SNPs prevalent in alcoholics for their effects on an alternative promoter that would lead to the production of the NH2-terminally truncated protein NBCn1N450, missing the first 450 amino acids. Analysis of the transcription start site database and a promoter prediction algorithm identified a cluster of three promoters in intron 7 and two short CpG-rich sites in intron 6. The promoter closest to rs3278 showed strong transcription activity in luciferase reporter gene assays. Major-to-minor allele substitution at rs3278 resulted in increased transcription activity. Equivale...
Source: Physiological Genomics - March 13, 2017 Category: Genetics & Stem Cells Authors: Park, H. J., Lee, S., Ju, E., Jones, J. A., Choi, I. Tags: Research Articles Source Type: research
Limited potential of genetic predisposition scores to predict muscle mass and strength performance in Flemish Caucasians between 19 and 73 years of age
Since both muscle mass and strength performance are polygenic in nature, the current study compared four genetic predisposition scores (GPS) in their ability to predict these phenotypes. Data were gathered within the framework of the first-generation Flemish Policy Research Centre "Sport, Physical Activity and Health" (2002–2004). Results are based on muscle characteristics data of 565 Flemish Caucasians (19–73 yr, 365 men). Skeletal muscle mass was determined from bioelectrical impedance. The Biodex dynamometer was used to measure isometric (PTstatic120°) and isokinetic strength (PTdynamic60° and PTdyn...
Source: Physiological Genomics - March 13, 2017 Category: Genetics & Stem Cells Authors: Charlier, R., Caspers, M., Knaeps, S., Mertens, E., Lambrechts, D., Lefevre, J., Thomis, M. Tags: Research Articles Source Type: research
Data integration in physiology using Bayes rule and minimum Bayes factors: deubiquitylating enzymes in the renal collecting duct
A major challenge in physiology is to exploit the many large-scale data sets available from "-omic" studies to seek answers to key physiological questions. In previous studies, Bayes’ theorem has been used for this purpose. This approach requires a means to map continuously distributed experimental data to probabilities (likelihood values) to derive posterior probabilities from the combination of prior probabilities and new data. Here, we introduce the use of minimum Bayes’ factors for this purpose and illustrate the approach by addressing a physiological question, "Which deubiquitylating enzymes (DUBs) encoded...
Source: Physiological Genomics - February 28, 2017 Category: Genetics & Stem Cells Authors: Xue, Z., Chen, J.-X., Zhao, Y., Medvar, B., Knepper, M. A. Tags: Innovative Methodology Source Type: research
Fine-mapping of genes determining extrafusal fiber properties in murine soleus muscle
This study aimed to map quantitative trait loci (QTL) affecting differences in soleus muscle fiber traits between the LG/J and SM/J mouse strains. Fiber number, CSA, and proportion of oxidative type I fibers were assessed in the soleus of 334 genotyped female and male mice of the F34 generation of advanced intercross lines (AIL) derived from the LG/J and SM/J strains. To increase the QTL detection power, these data were combined with 94 soleus samples from the F2 intercross of the same strains. Transcriptome of the soleus muscle of LG/J and SM/J females was analyzed by microarray. Genome-wide association analysis mapped fo...
Source: Physiological Genomics - February 28, 2017 Category: Genetics & Stem Cells Authors: Carroll, A. M., Cheng, R., Collie-Duguid, E. S. R., Meharg, C., Scholz, M. E., Fiering, S., Fields, J. L., Palmer, A. A., Lionikas, A. Tags: Research Articles Source Type: research
Mycophenolate mofetil prevents cerebrovascular injury in stroke-prone spontaneously hypertensive rats
Stroke-prone spontaneously hypertensive rats (SHR-A3) develop strokes and progressive kidney disease as a result of naturally occurring genetic variations. We recently identified genetic variants in immune signaling pathways that contribute to end-organ injury. The present study was designed to test the hypothesis that a dysregulated immune response promotes stroke susceptibility. We salt-loaded 20 wk old male SHR-A3 rats and treated them with the immunosuppressant mycophenolate mofetil (MMF, 25 mg/kg/day po) (n = 8) or vehicle (saline) (n = 9) for 8 wk. Blood pressure (BP) was measured weekly by telemetry. Compared with v...
Source: Physiological Genomics - February 28, 2017 Category: Genetics & Stem Cells Authors: Dhande, I. S., Zhu, Y., Braun, M. C., Hicks, M. J., Wenderfer, S. E., Doris, P. A. Tags: Research Articles Source Type: research
GSTP1 c.313A>G polymorphism in Russian and Polish athletes
The GSTP1 gene encodes glutathione S-transferase P1, which is a member of the glutathione S-transferases (GSTs), a family of enzymes playing an important role in detoxification and in the antioxidant defense system. There is some evidence indicating that GSTP1 c.313A>G polymorphism may be beneficial for exercise performance. Therefore, we decided to verify the association between the frequency of GSTP1 c.313A>G variants, physical performance, and athletes' status in two cohorts: in a group of Russian athletes (n = 507) and in an independent population of Polish athletes (n = 510) in a replication study. The initial a...
Source: Physiological Genomics - February 28, 2017 Category: Genetics & Stem Cells Authors: Zarebska, A., Jastrzebski, Z., Ahmetov, I. I., Zmijewski, P., Cieszczyk, P., Leonska-Duniec, A., Sawczuk, M., Leznicka, K., Trybek, G., Semenova, E. A., Maciejewska-Skrendo, A. Tags: Research Articles Source Type: research
Inflammation and vascular smooth muscle cell dedifferentiation following carotid artery ligation
Following vascular injury medial smooth muscle cells dedifferentiate and migrate through the internal elastic lamina where they form a neointima. The goal of the current study was to identify changes in gene expression that occur before the development of neointima and are associated with the early response to injury. Vascular injury was induced in C57BL/6 mice and in Myh11-creER(T2) mTmG reporter mice by complete ligation of the left carotid artery. Reporter mice were used to visualize cellular changes in the injured vessels. Total RNA was isolated from control carotid arteries or from carotid arteries 3 days following li...
Source: Physiological Genomics - February 28, 2017 Category: Genetics & Stem Cells Authors: Herring, B. P., Hoggatt, A. M., Griffith, S. L., McClintick, J. N., Gallagher, P. J. Tags: Research Articles Source Type: research
Single cell transcriptomic profiling of mouse pancreatic progenitors
The heterogeneity of the developing pancreatic epithelium and low abundance of endocrine progenitors limit the information derived from traditional expression studies. To identify genes that characterize early developmental tissues composed of multiple progenitor lineages, we applied single-cell RNA-Seq to embryonic day (e)13.5 mouse pancreata and performed integrative analysis with single cell data from mature pancreas. We identified subpopulations expressing macrophage or endothelial markers and new pancreatic progenitor markers. We also identified potential α-cell precursors expressing glucagon (Gcg) among the e13...
Source: Physiological Genomics - February 13, 2017 Category: Genetics & Stem Cells Authors: Stanescu, D. E., Yu, R., Won, K.-J., Stoffers, D. A. Tags: Research Articles Source Type: research
Alterations in the gut microbiota can elicit hypertension in rats
Gut dysbiosis has been linked to cardiovascular diseases including hypertension. We tested the hypothesis that hypertension could be induced in a normotensive strain of rats or attenuated in a hypertensive strain of rats by exchanging the gut microbiota between the two strains. Cecal contents from spontaneously hypertensive stroke prone rats (SHRSP) were pooled. Similarly, cecal contents from normotensive WKY rats were pooled. Four-week-old recipient WKY and SHR rats, previously treated with antibiotics to reduce the native microbiota, were gavaged with WKY or SHRSP microbiota, resulting in four groups; WKY with WKY microb...
Source: Physiological Genomics - February 13, 2017 Category: Genetics & Stem Cells Authors: Adnan, S., Nelson, J. W., Ajami, N. J., Venna, V. R., Petrosino, J. F., Bryan, R. M., Durgan, D. J. Tags: Research Articles Source Type: research
Roles of estrogen receptor-alpha in mediating life span: the hypothalamic deregulation hypothesis
In several species caloric restriction (CR) extends life span. In this paper we integrate data from studies on CR and other sources to articulate the hypothalamic deregulation hypothesis by which estrogen receptor-alpha (ER-α) signaling in the hypothalamus and limbic system affects life span under the stress of CR in mammals. ER-α is one of two principal estrogen-binding receptors differentially expressed in the amygdala, hippocampus, and several key hypothalamic nuclei: the arcuate nucleus (ARN), preoptic area (POA), ventromedial nucleus (VMN), antero ventral periventricular nucleus (AVPV), paraventricular nuc...
Source: Physiological Genomics - January 31, 2017 Category: Genetics & Stem Cells Authors: Gouw, A. M., Efe, G., Barakat, R., Preecha, A., Mehdizadeh, M., Garan, S. A., Brooks, G. A. Tags: Review Source Type: research
Pharmacogenetics and pathophysiology of CACNA1S mutations in malignant hyperthermia
A review of the pharmacogenetics (PGt) and pathophysiology of calcium voltage-gated channel subunit alpha1 S (CACNA1S) mutations in malignant hyperthermia susceptibility type 5 (MHS5; MIM #60188) is presented. Malignant hyperthermia (MH) is a life-threatening hypermetabolic state of skeletal muscle usually induced by volatile, halogenated anesthetics and/or the depolarizing neuromuscular blocker succinylcholine. In addition to ryanodine receptor 1 (RYR1) mutations, several CACNA1S mutations are known to be risk factors for increased susceptibility to MH (MHS). However, the presence of these pathogenic CACNA1S gene variatio...
Source: Physiological Genomics - January 31, 2017 Category: Genetics & Stem Cells Authors: Beam, T. A., Loudermilk, E. F., Kisor, D. F. Tags: Review Source Type: research
Differentially expressed genes and gene networks involved in pig ovarian follicular atresia
The objective of this study was to analyze global gene expression in pig granulosa cells of ovarian follicles during atresia. The transcriptome analysis was performed on a 9,216 cDNA microarray to identify gene networks and candidate genes involved in pig ovarian follicular atresia. We found 1,684 significantly regulated genes to be differentially regulated between small healthy follicles and small atretic follicles. Among them, 287 genes had a fold-change higher than two between the two follicle groups. Eleven genes (DKK3, GADD45A, CAMTA2, CCDC80, DAPK2, ECSIT, MSMB, NUPR1, RUNX2, SAMD4A, and ZNF628) having a fold-change ...
Source: Physiological Genomics - January 31, 2017 Category: Genetics & Stem Cells Authors: Terenina, E., Fabre, S., Bonnet, A., Monniaux, D., Robert-Granie, C., SanCristobal, M., Sarry, J., Vignoles, F., Gondret, F., Monget, P., Tosser-Klopp, G. Tags: Research Articles Source Type: research
