Abstract P180: Proximity To Telomeres Or A+t Content Suffices To Project Monogenic Hypertension At An 80 % Matching Rate

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Ian McKnight ◽  
Regan Raines ◽  
Hunter White ◽  
Joon W Shim
Keyword(s):  
Essential Hypertension ◽  
Stochastic Approach ◽  
Genetic Mutations ◽  
Age Related ◽  
Human Genes ◽  
Genomic Analyses ◽  
Two Factors ◽  
Degenerative Disorder ◽  
Monogenic Hypertension

Hypertension remains the single biggest risk factor contributing to the global burden of disease and mortality. Despite the prevalence of individuals with elevated blood pressure, the role of genetics in hypertension is poorly understood. We have recently demonstrated that mutations causative to the congenital disorder can be projected by a stochastic approach centered on chromosomal characteristics of proximity to telomeres (F(i)) and adenine and thymine (A+T) content (F(ii)). Here, we investigated the two chromosomal factors, F(i) and F(ii), to determine whether they are associated with high mutation rates in human genes related to essential and monogenic hypertension (MH). In essential hypertension, the mismatch of two factors and the disease as well as the correlation between the full-length size of the genes and A+T content was either unexpectedly low (~53%) or statistically insignificant. When we examined 79 genes susceptible to MH and contributing to the genetic architecture of hypertension focusing on the factor-disease matching rate, 64 of 79 genes exclusively satisfied either the F(i) or F(ii) condition. Unlike the previous study on essential hypertension, a quarter of these genes displayed high A+T content at higher than 59%. 16% of genes (13 of 79) associated with hypertension met neither F(i) nor F(ii). Furthermore, 2 of 79 genes met both F(i) and F(ii). Our analysis suggests that these two factors can explain the cause of genetic mutations in 79 loci proposed in MH roughly at an 80% rate. In comparison, these two factors proposed can only explain the cause of idiopathic disease such as essential hypertension at a rate comparable to flipping a coin (50 %). The proposed genomic analyses demonstrate an intermediate matching rate or a mediocre predictability (~75% or less) between the cause of genetic mutations and the disease in the cases of congenital heart disease, thoracic aortic aneurysm, and age-related degenerative disorder.

scholarly journals Role of gene length in control of human gene expression: chromosome-specific and tissue-specific effects

2020 ◽  
Author(s):  
Jay C. Brown
Keyword(s):  
Gene Expression ◽  
Gene Length ◽  
Control Of Gene Expression ◽  
Specific Effects ◽  
New Information ◽  
Human Genes ◽  
Two Factors ◽  
Highly Expressed Genes ◽  
Long Genes

AbstractBackgroundThis study was carried out to pursue the observation that the level of gene expression is affected by gene length in the genomes of higher vertebrates. As transcription is a time-dependent process, it is expected that gene expression will be inversely related to gene length, and this is found to be the case. Here I describe the results of studies performed with the human genome to test whether the gene length/gene expression linkage is affected by two factors, the chromosome where the gene is located and the tissue where it is expressed.Experimental designStudies were carried out with a database of 2413 human genes that were divided into short, mid-length and long groups. Each of the 24 human chromosomes was then characterized according to the proportion of each gene length group present. A similar analysis was performed with 19 human tissues. The proportion of short, mid-length and long genes was noted for each tissue.ResultsBoth chromosome and tissue studies revealed new information about the role of gene length in control of gene expression. Chromosome studies led to the identification of two chromosome populations that differ in the level of short gene expression. Tissue studies support the conclusion that short, highly expressed genes are enriched in tissues that produce protein products that are exported from the host cell.

scholarly journals Telomere Length Reprogramming in Embryos and Stem Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Keri Kalmbach ◽  
LeRoy G. Robinson ◽  
Fang Wang ◽  
Lin Liu ◽  
David Keefe
Keyword(s):  
Stem Cells ◽  
Telomere Length ◽  
Genetic Mutations ◽  
Subsequent Generation ◽  
Linear Chromosome ◽  
Age Related ◽  
Early Embryos

Telomeres protect and cap linear chromosome ends, yet these genomic buffers erode over an organism’s lifespan. Short telomeres have been associated with many age-related conditions in humans, and genetic mutations resulting in short telomeres in humans manifest as syndromes of precocious aging. In women, telomere length limits a fertilized egg’s capacity to develop into a healthy embryo. Thus, telomere length must be reset with each subsequent generation. Although telomerase is purportedly responsible for restoring telomere DNA, recent studies have elucidated the role of alternative telomeres lengthening mechanisms in the reprogramming of early embryos and stem cells, which we review here.

scholarly journals Factors Associated with Mutations: Their Matching Rates to Cardiovascular and Neurological Diseases

2021 ◽  
Vol 22 (10) ◽  
pp. 5057
Author(s):  
Hannah B. Lucas ◽  
Ian McKnight ◽  
Regan Raines ◽  
Abdullah Hijazi ◽  
Christoph Hart ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Nucleotide Polymorphisms ◽  
Factors Associated ◽  
Genome Data ◽  
Rare Mutations ◽  
Human Genes ◽  
A Genome ◽  
Two Factors ◽  
Vascular Stiffening ◽  
Monogenic Hypertension

Monogenic hypertension is rare and caused by genetic mutations, but whether factors associated with mutations are disease-specific remains uncertain. Given two factors associated with high mutation rates, we tested how many previously known genes match with (i) proximity to telomeres or (ii) high adenine and thymine content in cardiovascular diseases (CVDs) related to vascular stiffening. We extracted genomic information using a genome data viewer. In human chromosomes, 64 of 79 genetic loci involving >25 rare mutations and single nucleotide polymorphisms satisfied (i) or (ii), resulting in an 81% matching rate. However, this high matching rate was no longer observed as we checked the two factors in genes associated with essential hypertension (EH), thoracic aortic aneurysm (TAA), and congenital heart disease (CHD), resulting in matching rates of 53%, 70%, and 75%, respectively. A matching of telomere proximity or high adenine and thymine content projects the list of loci involving rare mutations of monogenic hypertension better than those of other CVDs, likely due to adoption of rigorous criteria for true-positive signals. Our data suggest that the factor–disease matching rate is an accurate tool that can explain deleterious mutations of monogenic hypertension at a >80% match—unlike the relatively lower matching rates found in human genes of EH, TAA, CHD, and familial Parkinson’s disease.

scholarly journals Revisiting the Role of GSK3, A Modulator of Innate Immunity, in Idiopathic Inclusion Body Myositis

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3255
Author(s):  
Manuela Piazzi ◽  
Alberto Bavelloni ◽  
Vittoria Cenni ◽  
Irene Faenza ◽  
William L. Blalock
Keyword(s):  
Inclusion Body ◽  
Inclusion Bodies ◽  
Inclusion Body Myositis ◽  
Glycogen Synthase ◽  
Slowing Down ◽  
Age Related ◽  
Degenerative Disorders ◽  
Sporadic Inclusion Body Myositis ◽  
Degenerative Disorder

Idiopathic or sporadic inclusion body myositis (IBM) is the leading age-related (onset > 50 years of age) autoimmune muscular pathology, resulting in significant debilitation in affected individuals. Once viewed as primarily a degenerative disorder, it is now evident that much like several other neuro-muscular degenerative disorders, IBM has a major autoinflammatory component resulting in chronic inflammation-induced muscle destruction. Thus, IBM is now considered primarily an inflammatory pathology. To date, there is no effective treatment for sporadic inclusion body myositis, and little is understood about the pathology at the molecular level, which would offer the best hopes of at least slowing down the degenerative process. Among the previously examined potential molecular players in IBM is glycogen synthase kinase (GSK)-3, whose role in promoting TAU phosphorylation and inclusion bodies in Alzheimer’s disease is well known. This review looks to re-examine the role of GSK3 in IBM, not strictly as a promoter of TAU and Abeta inclusions, but as a novel player in the innate immune system, discussing some of the recent roles discovered for this well-studied kinase in inflammatory-mediated pathology.

scholarly journals Role of Gene Length in Control of Human Gene Expression: Chromosome-Specific and Tissue-Specific Effects

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Jay C. Brown
Keyword(s):  
Gene Expression ◽  
Expression Level ◽  
Gene Length ◽  
Control Of Gene Expression ◽  
Tissue Specific ◽  
Specific Effects ◽  
Human Genes ◽  
Two Factors ◽  
High Level

This study was carried out to pursue the observation that the level of gene expression is affected by gene length in the human genome. As transcription is a time-dependent process, it is expected that gene expression will be inversely related to gene length, and this is found to be the case. Here, I describe the results of studies performed to test whether the gene length/gene expression linkage is affected by two factors, the chromosome where the gene is located and the tissue where it is expressed. Studies were performed with a database of 3538 human genes that were divided into short, midlength, and long groups. Chromosome groups were then compared in the expression level of genes with the same length. A similar analysis was performed with 19 human tissues. Tissue-specific groups were compared in the expression level of genes with the same length. Both chromosome and tissue studies revealed new information about the role of gene length in control of gene expression. Chromosome studies led to the identification of two chromosome populations that differ in the expression level of short genes. A high level of expression was observed in chromosomes 2-10, 12-15, and 18 and a low level in 1, 11, 16-17, 19-20, 22, and 24. Studies with tissue-specific genes led to the identification of two tissues, brain and liver, which differ in the expression level of short genes. The results are interpreted to support the view that the level of a gene’s expression can be affected by the chromosome and the tissue where the gene is transcribed.

Age-related memory deficit: Role of study time and encoding strategies

2010 ◽  
Author(s):  
Charlotte Froger ◽  
Badiaa Bouazzaoui ◽  
Laurence Taconnat
Keyword(s):  
Memory Deficit ◽  
Study Time ◽  
Age Related ◽  
Encoding Strategies

ROLE OF ADDED PHOSPHOGYPSUM AND HUMIC ACIDS IN THE KINETIC RELEASE OF SALT FROM SALT AFFECTED SOIL (SALINE – SODIC)

2020 ◽  
pp. 15-27
Keyword(s):  
Electrical Conductivity ◽  
Humic Acids ◽  
Release Rate ◽  
Release Kinetics ◽  
Sodium Adsorption Ratio ◽  
Salt Affected Soil ◽  
Two Factors ◽  
Dissolved Ions ◽  
Kinetic Release

In order to study the effect of phosphogypsum and humic acids in the kinetic release of salt from salt-affected soil, a laboratory experiment was conducted in which columns made from solid polyethylene were 60.0 cm high and 7.1 cm in diameter. The columns were filled with soil so that the depth of the soil was 30 cm inside the column, the experiment included two factors, the first factor was phosphogypsum and was added at levels 0, 5, 10 and 15 tons ha-1 and the second-factor humic acids were added at levels 0, 50, 100 and 150 kg ha-1 by mixing them with the first 5 cm of column soil and one repeater per treatment. The continuous leaching method was used by using an electrolytic well water 2.72 dS m-1. Collect the leachate daily and continue the leaching process until the arrival of the electrical conductivity of the filtration of leaching up to 3-5 dS m-1. The electrical conductivity and the concentration of positive dissolved ions (Ca, Mg, Na) were estimated in leachate and the sodium adsorption ratio (SAR) was calculated. The results showed that the best equation for describing release kinetics of the salts and sodium adsorption ratio in soil over time is the diffusion equation. Increasing the level of addition of phosphogypsum and humic acids increased the constant release velocity (K) of salts and the sodium adsorption ratio. The interaction between phosphogypsum and humic acids was also affected by the constant release velocity of salts and the sodium adsorption ratio. The constant release velocity (K) of the salts and the sodium adsorption ratio at any level of addition of phosphogypsum increased with the addition of humic acids. The highest salts release rate was 216.57 in PG3HA3, while the lowest rate was 149.48 in PG0HA0. The highest release rate of sodium adsorption ratio was 206.09 in PG3HA3, while the lowest rate was 117.23 in PG0HA0.

Papillon-Lefevre Syndrome: Challenge for Periodontal Management

2019 ◽  
Vol 3 (2) ◽  
pp. 84-86
Author(s):  
Krishna Prasad Lamichhane ◽  
Shaili Pradhan ◽  
Ranjita Shreshta Gorkhali ◽  
Pramod Kumar Koirala
Keyword(s):  
Significant Role ◽  
Autosomal Recessive ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Genetic Mutations ◽  
Rare Autosomal Recessive Disorder ◽  
Diagnosis And Management ◽  
Periodontal Destruction ◽  
Palmoplantar Keratosis

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder associated with rapidly progressing periodontitis leading to premature loss of deciduous and permanent dentition and diffuse palmoplantar keratosis. Immunologic alterations, genetic mutations, and role of bacteria are some aetiologic factors. Patients present with early periodontal destruction, so periodontists play a significant role in diagnosis and management. This paper reports a case of Papillon- Lefevre syndrome with its clinical manifestations and challenges for periodontal management which was diagnosed in dental department.

Sign in / Sign up

Export Citation Format

Share Document