scholarly journals Natural selection at the RASGEF1C (GGC) repeat in human and divergent genotypes in late-onset neurocognitive disorder.

2021 ◽  
Author(s):  
Zahra Jafarian ◽  
Safoura Khamse ◽  
Hossein Afshar ◽  
Hamid Reza Khorram Khorshid ◽  
Ahmad Delbari ◽  
...  
Keyword(s):  
Natural Selection ◽  
Late Onset ◽  
Core Promoter ◽  
Human Subjects ◽  
Primate Species ◽  
Control Group ◽  
Specific Gene ◽  
Repeat Allele ◽  
The Status ◽  
Significant Divergence

Abstract Expression dysregulation of the neuron-specific gene, RASGEF1C (RasGEF Domain Family Member 1C), occurs in late-onset neurocognitive disorders (NCDs), such as Alzheimer’s disease. This gene contains a (GGC)13, spanning its core promoter and 5′ untranslated region (RASGEF1C-201 ENST00000361132.9). Here we sequenced the (GGC)-repeat in a sample of human subjects (N=269), consisting of late-onset NCDs (N=115) and controls (N=154). We also studied the status of this STR across various primate and non-primate species based on Ensembl 103. The 6-repeat allele was the predominant allele in the controls (frequency=0.85) and NCD patients (frequency=0.78). The NCD genotype compartment consisted of an excess of genotypes that lacked the 6-repeat (divergent genotypes) (Mid-P exact=0.004). A number of those genotypes were not detected in the control group (Mid-P exact=0.007). The RASGEF1C (GGC)-repeat expanded beyond 2-repeats specifically in primates, and was at maximum length in human. We conclude that there is natural selection for the 6-repeat allele of the RASGEF1C (GGC)-repeat in human, and significant divergence from that allele in late-onset NCDs. STR alleles that are predominantly abundant in human and genotypes that deviate from those alleles are underappreciated features, which may have deep evolutionary and pathological consequences in human.

scholarly journals Natural selection at the RASGEF1C (GGC) repeat in human and divergent genotypes in late-onset neurocognitive disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Z. Jafarian ◽  
S. Khamse ◽  
H. Afshar ◽  
H.R. Khorram Khorshid ◽  
A. Delbari ◽  
...  
Keyword(s):  
Natural Selection ◽  
Late Onset ◽  
Core Promoter ◽  
Human Subjects ◽  
Primate Species ◽  
Control Group ◽  
Specific Gene ◽  
Repeat Allele ◽  
The Status ◽  
Significant Divergence

AbstractExpression dysregulation of the neuron-specific gene, RASGEF1C (RasGEF Domain Family Member 1C), occurs in late-onset neurocognitive disorders (NCDs), such as Alzheimer’s disease. This gene contains a (GGC)13, spanning its core promoter and 5′ untranslated region (RASGEF1C-201 ENST00000361132.9). Here we sequenced the (GGC)-repeat in a sample of human subjects (N = 269), consisting of late-onset NCDs (N = 115) and controls (N = 154). We also studied the status of this STR across various primate and non-primate species based on Ensembl 103. The 6-repeat allele was the predominant allele in the controls (frequency = 0.85) and NCD patients (frequency = 0.78). The NCD genotype compartment consisted of an excess of genotypes that lacked the 6-repeat (divergent genotypes) (Mid-P exact = 0.004). A number of those genotypes were not detected in the control group (Mid-P exact = 0.007). The RASGEF1C (GGC)-repeat expanded beyond 2-repeats specifically in primates, and was at maximum length in human. We conclude that there is natural selection for the 6-repeat allele of the RASGEF1C (GGC)-repeat in human, and significant divergence from that allele in late-onset NCDs. STR alleles that are predominantly abundant and genotypes that deviate from those alleles are underappreciated features, which may have deep evolutionary and pathological consequences.

scholarly journals Natural selection at the RASGEF1C (GGC) repeat in human and divergent genotypes in late-onset neurocognitive disorder.

2021 ◽  
Author(s):  
Zahra Jafarian ◽  
Safoura Khamse ◽  
Hossein Afshar ◽  
Hamid Reza Khorram Khorshid ◽  
Ahmad Delbari ◽  
...  
Keyword(s):  
Natural Selection ◽  
Late Onset ◽  
Core Promoter ◽  
Human Subjects ◽  
Primate Species ◽  
Control Group ◽  
Specific Gene ◽  
Repeat Allele ◽  
The Status ◽  
Significant Divergence

Abstract Expression dysregulation of the neuron-specific gene, RASGEF1C (RasGEF Domain Family Member 1C), occurs in late-onset neurocognitive disorders (NCDs), such as Alzheimer’s disease. This gene contains a (GGC)13, spanning its core promoter and 5′ untranslated region (RASGEF1C-201 ENST00000361132.9). Here we sequenced the (GGC)-repeat in a sample of human subjects (N = 269), consisting of late-onset NCDs (N = 115) and controls (N = 154). We also studied the status of this STR across various primate and non-primate species based on Ensembl 103. The 6-repeat allele was the predominant allele in the controls (frequency = 0.85) and NCD patients (frequency = 0.78). The NCD genotype compartment consisted of an excess of genotypes that lacked the 6-repeat (divergent genotypes) (Mid-P exact = 0.004). A number of those genotypes were not detected in the control group (Mid-P exact = 0.007). The RASGEF1C (GGC)-repeat expanded beyond 2-repeats specifically in primates, and was at maximum length in human. We conclude that there is natural selection for the 6-repeat allele of the RASGEF1C (GGC)-repeat in human, and significant divergence from that allele in late-onset NCDs. STR alleles that are predominantly abundant and genotypes that deviate from those alleles are underappreciated features, which may have deep evolutionary and pathological consequences.

scholarly journals Natural Selection at an Exceptionally Long GGC Repeat in the Human RASGEF1C and Divergent Genotypes in Late-onset Neurocognitive Disorder

2021 ◽  
Author(s):  
Z Jafarian ◽  
S Khamse ◽  
H Afshar ◽  
Khorram Khorshid HR ◽  
A Delbari ◽  
...  
Keyword(s):  
Natural Selection ◽  
Evolutionary Biology ◽  
Late Onset ◽  
Core Promoter ◽  
Human Subjects ◽  
Specific Gene ◽  
Protein Coding ◽  
Repeat Allele ◽  
Complex Disorders ◽  
Selection For

Abstract Across the human protein-coding genes, the neuron-specific gene, RASGEF1C, contains the longest (GGC)-repeat, spanning its core promoter and 5′ untranslated region (RASGEF1C-201 ENST00000361132.9). RASGEF1C expression dysregulation occurs in late-onset neurocognitive disorders (NCDs), such as Alzheimer’s disease. Here we sequenced the GGC-repeat in a sample of human subjects (N = 269), consisting of late-onset NCDs (N = 115) and controls (N = 154). We also studied the status of this STR across vertebrates. The 6-repeat allele of this repeat was the predominant allele in the controls (frequency = 0.85) and NCD patients (frequency = 0.78). The NCD genotype compartment consisted of an excess of genotypes that lacked the 6-repeat (Mid-P exact = 0.004). We also detected divergent genotypes that were present in five NCD patients and not in the controls (Mid-P exact = 0.007). This STR expanded beyond 2-repeats specifically in primates, and was at maximum length in human. We conclude that there is natural selection for the 6-repeat allele of the RASGEF1C (GGC)-repeat in human, and significant divergence from that allele in late-onset NCDs. Indication of natural selection for predominantly abundant STR alleles and divergent genotypes enhance the perspective of evolutionary biology and disease pathogenesis in human complex disorders.

scholarly journals Natural Selection at the NHLH2 Core Promoter Exceptionally Long CA-Repeat in Human and Disease-Only Genotypes in Late-Onset Neurocognitive Disorder

Gerontology ◽  
2020 ◽  
Vol 66 (5) ◽  
pp. 514-522 ◽  
Author(s):  
Hossein Afshar ◽  
Fatemeh Adelirad ◽  
Ali Kowsari ◽  
Naser Kalhor ◽  
Ahmad Delbari ◽  
...  
Keyword(s):  
Natural Selection ◽  
Late Onset ◽  
Core Promoter ◽  
Neurocognitive Disorder ◽  
Ca Repeat

scholarly journals Novel biological implication of a strictly monomorphic GCC repeat in the human PRKACB gene

2021 ◽  
Author(s):  
Safoura Khamse ◽  
Zahra Jafarian ◽  
Ali Bozorgmehr ◽  
Mostafa Tavakoli ◽  
Hossein Afshar Iranian ◽  
...  
Keyword(s):  
Late Onset ◽  
Human Subjects ◽  
Three Dimensional ◽  
Dna Structure ◽  
Dimensional Structure ◽  
Protein Coding ◽  
Three Dimensional Structure ◽  
Significant Divergence ◽  
The Impact ◽  
The Brain

Abstract Across human protein-coding genes, PRKACB (Protein Kinase CAMP-Activated Catalytic Subunit Beta) contains one of the longest GCC-repeats, and is predominantly expressed in the brain. Here we studied this STR in 300 human subjects, consisting of late-onset neurocognitive disorder (NCD) (N = 150) and controls (N = 150). We also studied the impact of this STR on the three-dimensional structure of DNA. While the PRKACB GCC-STR was strictly monomorphic at 7-repeats, we detected two 7/8 genotypes only in the NCD group. In comparison to all other lengths, (GCC)7 had the least effect on the three-dimensional structure of DNA, evidenced by minimal divergence between 0 and 7-repeats (divergence score = 0.04) and significant divergence between 0 and 8 repeats (divergence score = 0.50). A similar inert effect to the GCC-repeat was not detected in other classes of STRs such as GA and CA repeats. In conclusion, we report monomorphism of an exceptionally long GCC repeat in the PRKACB gene in human, its inert effect on DNA structure, and divergence in two cases of late-onset NCD. This is the first indication of natural selection for an exceptionally long monomorphic GCC-repeat, which probably evolved to function as an “epigenetic knob”, without changing the regional DNA structure.

scholarly journals Novel implications of a strictly monomorphic (GCC) repeat in the human PRKACB gene

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Safoura Khamse ◽  
Zahra Jafarian ◽  
Ali Bozorgmehr ◽  
Mostafa Tavakoli ◽  
Hossein Afshar ◽  
...  
Keyword(s):  
Tandem Repeats ◽  
Late Onset ◽  
Core Promoter ◽  
Human Subjects ◽  
3D Structure ◽  
Three Dimensional ◽  
Dna Structure ◽  
Neuroprotective Effects ◽  
The Impact ◽  
The Brain

AbstractPRKACB (Protein Kinase CAMP-Activated Catalytic Subunit Beta) is predominantly expressed in the brain, and regulation of this gene links to neuroprotective effects against tau and Aβ-induced toxicity. Here we studied a (GCC)-repeat spanning the core promoter and 5′ UTR of this gene in 300 human subjects, consisting of late-onset neurocognitive disorder (NCD) (N = 150) and controls (N = 150). We also implemented several models to study the impact of this repeat on the three-dimensional (3D) structure of DNA. While the PRKACB (GCC)-repeat was strictly monomorphic at 7-repeats, we detected two 7/8 genotypes only in the NCD group. In all examined models, the (GCC)7 and its periodicals had the least range of divergence variation on the 3D structure of DNA in comparison to the 8-repeat periodicals and several hypothetical repeat lengths. A similar inert effect on the 3D structure was not detected in other classes of short tandem repeats (STRs) such as GA and CA repeats. In conclusion, we report monomorphism of a long (GCC)-repeat in the PRKACB gene in human, its inert effect on DNA structure, and enriched divergence in late-onset NCD. This is the first indication of natural selection for a monomorphic (GCC)-repeat, which probably evolved to function as an “epigenetic knob”, without changing the regional DNA structure.

NATRIURETIC PEPTIDES LEVEL AND THE STATUS OF THE RENIN – ANGIOTENSIN-ALDOSTERONE SYSTEM IN CHRONIC KIDNEY DISEASE IN PATIENTS WITH CONGENITAL MALFORMATIONS OF THE URINARY SYSTEM

2018 ◽  
Vol 22 (5) ◽  
pp. 45-50
Author(s):  
A. M. Mambetova ◽  
A. M. Inarokova ◽  
N. N. Shabalova ◽  
D. V. Bizheva ◽  
A. T. Mahiyeva
Keyword(s):  
Congenital Malformations ◽  
Control Group ◽  
Healthy Children ◽  
Urinary System ◽  
Renin Angiotensin Aldosterone System ◽  
Natriuretic Hormone ◽  
Renin Angiotensin ◽  
Group I ◽  
The Status ◽  
Sick Children

THE AIM. To determine the concentration of natriuretic peptide in the blood serum in children with congenital malformations of the urinary system (CM US) and to compare with the activity of renin-angiotensin-aldosterone system (RAAS).MATERIALS AND METHODS.119 patients with CM US aged 3 to 18 years were examined. A control group of 10 clinically healthy children. 3 groups were assigned: group I – 55 children with  congenital vesicoureteral reflux, and group II – 34 children with  congenital hydronephrosis and ureterohydronephrosis, III group – 30 children with other forms of dysembryogenesis of the US. Following indicators were identified by ELISA in the blood: renin, aldosterone,  N – terminal propeptide natriuretic hormone (NT-рroВNР). RESULTS.NT-рroВNР, renin and aldosterone hyperproduction were diagnosed in 59,6%, 69,7%, 54.6 % of sick children relatively. Concentrations were higher in all variants of  malformations in comparison with the control group. Significant  differences were revealed in obstructive species, where arterial  hypertension (AH) was diagnosed more often. Patients with AH  recorded significantly higher concentrations of NT-proВNР and renin.CONCLUSION.The key point in pathological processes developmentand progression in the cardiovascular system and kidneys is the  activation of RAAS. The system of natriuretic factors is important in maintaining the compensated state of patients due to the blockade of RAAS.

Association of the CD14 C159T and the Toll-like receptor 4 Asp299Gly polymorphisms with various phenotypes of asthma in adults from Crimea

2020 ◽  
Vol 41 (2) ◽  
pp. 134-140
Author(s):  
Yuriy Bisyuk ◽  
Andrew Dubovyi ◽  
Ilona DuBuske ◽  
Viktor Litus ◽  
Lawrence M. DuBuske
Keyword(s):  
Late Onset ◽  
Adult Population ◽  
Additive Models ◽  
Atopic Asthma ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Single Nucleotide ◽  
Gender And Age

Background: This study assessed gene polymorphisms of the CD14 receptor (C-159T) and Toll-like receptor 4 (Asp299Gly) in a patient population in Crimea, Ukraine, stratified by clinical (early versus late onset; frequent versus occasional relapses; fixed versus reversible obstruction) and immunologic (atopic versus nonatopic; eosinophilic; neutrophilic or paucigranulocytic inflammation) subtype. Methods: Two polymorphisms, CD14 C-159T and TLR4 Asp299Gly, were assessed in 331 patients with asthma. The control group included 285 volunteers who were nonatopic. The single nucleotide polymorphisms were studied by using polymerase chain reaction with electrophoretic detection. Results: There were increased odds of asthma development in patients with the Asp299Gly TLR4 mutation compared with the general population underdominant odds ratio (OR) 1.52 [95% confidence interval (CI), 1.00‐2.32] and overdominant (OR 1.55 [95% CI, 1.01‐2.38]) models after adjustment for gender and age. In addition, mutations in this gene decreased the odds of nonatopic asthma in underdominant (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.027), overdominant (OR 0.27 [95% CI, 0.07‐0.96]; p = 0.033), and log-additive models (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.026) compared with the atopic subgroup after adjustment for gender, age, number of exacerbations, and type of airway inflammation. Allele frequencies for CD14 and TLR4 polymorphisms did not show statistical differences between the patients with asthma and the control subjects. Conclusion: CD14 C-159T polymorphisms were not associated with asthma in the adult population in Crimea. TLR4 Asp299Gly polymorphisms were associated with asthma and with decreased odds of nonatopic asthma compared with atopic asthma in the adult population in Crimea.

Diagnostic value of assessment of Serum Cortisol, Hepcidin and Thyroid Hormone Levels in Neonates with Late Onset Sepsis

2020 ◽  
Vol 20 ◽  
Author(s):  
Adel Hagag ◽  
Mohamed S Elfarargy ◽  
Reham Lyonis ◽  
Ghada M Al-Ashmawy
Keyword(s):  
Thyroid Hormones ◽  
Antibiotic Therapy ◽  
Neonatal Sepsis ◽  
Late Onset ◽  
Serum Cortisol ◽  
Control Group ◽  
Serum Free ◽  
Group I ◽  
Late Onset Sepsis ◽  
Serum Hepcidin

Background: Neonatal sepsis is a clinical syndrome characterized by symptoms and signs of infection in the first twenty eight days of life. Serum thyroid, cortisol and hepcidin are affected by neonatal sepsis. Aim of the work: The aim of this study was to assess the predictive value of serum thyroid hormones including free triiodothyronine (free TT3) and free tetraiodothyronine (free TT4), serum cortisol and hepcidin levels through comparison of their concentrations between normal neonates and neonates with high probable late onset sepsis. Patients and Methods: This case control study was carried out on 40 neonates with suspected high probable late onset neonatal sepsis based on clinical and laboratory finding who were admitted to NICU of Pediatric Department, Tanta University, Egypt in the period from April 2017 to May 2019 (group I) and 40 healthy neonates matched in age and sex as a control group (group II). For patients and controls; blood culture, highly sensitive C‑reactive protein (H-s CRP), serum hepcidin, serum cortisol and thyroid hormones levels including free TT3 and free TT4 were assessed. Results: There were no significant differences between studied groups as regard weight, gestational age, sex and mode of delivery. H-s CRP, serum cortisol and hepcidin were significantly higher in group I than group II while serum free TT3 and free TT4 were significantly lower in group I compared with controls. There was significantly lower H-s CRP, serum hepcidin and cortisol and significantly higher serum free TT3 and free TT4 in group I after antibiotic therapy compared to the same group before treatment while there were no significant differences between group I after antibiotic therapy and control group as regard the same parameters. There were significant positive correlation between H-s CRP and serum hepcidin and cortisol in group I while there was significant negative correlation between H-s CRP and free TT3 and free TT4. ROC curve of specificity and sensitivity of H-s CRP, serum hepcidin, cortisol, free TT3 and free TT4 in prediction of neonatal sepsis shows that serum hepcidin had the highest sensitivity and specificity with 95% and 90% respectively followed by serum cortisol, H-s CRP, free TT3 and lastly free TT4. Conclusion and recommendations: Neonates with high probable sepsis had significantly higher serum cortisol and hepcidin and significantly lower free TT3 and free TT4 compared with healthy neonates. These findings may arouse our attention about the use of these markers in diagnosis of in neonatal sepsis which can lead to early treatment and subsequently better prognosis.

Efficacy of Ovsynch and Ovsynch Plus Protocol for Improvement of Fertility in Postpartum Sahiwal Cows

2019 ◽  
Vol 14 (04) ◽  
Author(s):  
J. P. Lakher ◽  
M. K. Awasthi ◽  
J. R. Khan ◽  
M. R. Poyam
Keyword(s):  
Fixed Time ◽  
Conception Rate ◽  
Control Group ◽  
Group Iii ◽  
Treatment Groups ◽  
Group I ◽  
Early Postpartum ◽  
The Status ◽  
Sahiwal Cows ◽  
And Control

The present study was conducted to investigate the efficacy of Ovsynch and Ovsynch plus protocol in postpartum (day 60) Sahiwal cows (n=18). Animals were randomly divided into three equal groups, viz., Ovsynch group Ovsynch plus group and Control group. Animals of group I (n = 6) were treated with traditional Ovsynch protocol. The animals (n = 6) of group II were treated with Ovsynch plus protocol which consisted of an initial intramuscular injection of eCG (Folligon) @ 250 IU on day 60 postpartum followed 3 days later by GPG (Ovsynch) protocol. In group-III Control, no treatment was given to animals (n = 6). Treated animals were inseminated at a fixed time between 14 and 20 hrs after second GnRH injection, irrespective of estrus detection. Blood samples were collected from each animal on days 50 and 60 postpartum to determine the status of cyclicity in animals based on serum concentrations of progesterone (P4). A third blood sample was collected on the day of prostaglandin treatment to determine the response of first GnRH injection. Four animals each were cyclic, and two were acyclic in both treatment groups. Four animals each responded to first GnRH treatment in both treatment groups. Similarly, two animals each got conceived giving conception rate of 50% (2/4) in each treatment. In the control group, one out of 6 animals got conceived yielding 16.66 % conception rate (1/6) during the study period. It may be thus concluded that Ovsynch and Ovsynch plus protocol may be used during the early postpartum period to improve the reproductive efficiency in postpartum Sahiwal cows.

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