scholarly journals Apolipoprotein E ( ApoE ) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy?

2015 ◽  
Vol 282 (1803) ◽  
pp. 20142395 ◽  
Author(s):  
Grazyna Jasienska ◽  
Peter T. Ellison ◽  
Andrzej Galbarczyk ◽  
Michal Jasienski ◽  
Malgorzata Kalemba-Drozdz ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Human Populations ◽  
Antagonistic Pleiotropy ◽  
Potential Candidate ◽  
High Frequencies ◽  
Potential Candidate Gene ◽  
Daily Data ◽  
Major Supplier ◽  
Menstruating Women ◽  
Cholesterol Precursor

The alleles that are detrimental to health, especially in older age, are thought to persist in populations because they also confer some benefits for individuals (through antagonistic pleiotropy). The ApoE4 allele at the ApoE locus, encoding apolipoprotein E (ApoE), significantly increases risk of poor health, and yet it is present in many populations at relatively high frequencies. Why has it not been replaced by natural selection with the health-beneficial ApoE3 allele? ApoE is a major supplier of cholesterol precursor for the production of ovarian oestrogen and progesterone, thus ApoE has been suggested as the potential candidate gene that may cause variation in reproductive performance. Our results support this hypothesis showing that in 117 regularly menstruating women those with genotypes with at least one ApoE4 allele had significantly higher levels of mean luteal progesterone (144.21 pmol l −1 ) than women with genotypes without ApoE4 (120.49 pmol l −1 ), which indicates higher potential fertility. The hormonal profiles were based on daily data for entire menstrual cycles. We suggest that the finding of higher progesterone in women with ApoE4 allele could provide first strong evidence for an evolutionary mechanism of maintaining the ancestral and health-worsening ApoE4 allele in human populations.

scholarly journals An ancient fecundability-associated polymorphism creates a new GATA2 binding site in a distal enhancer of HLA-F

2018 ◽  
Author(s):  
Katelyn M. Mika ◽  
Xilong Li ◽  
Francesco J. DeMayo ◽  
Vincent J. Lynch
Keyword(s):  
Binding Site ◽  
Stromal Cells ◽  
Evolutionary History ◽  
Reproductive Traits ◽  
Human Populations ◽  
Antagonistic Pleiotropy ◽  
Distal Enhancer ◽  
High Frequencies ◽  
History Of ◽  
Female Reproductive Traits

AbstractVariation in female reproductive traits such as fertility, fecundity, and fecundability are heritable in humans, but identifying and functionally characterizing genetic variants associated with these traits has been challenging. Here we explore the functional significance and evolutionary history of a G/A polymorphism of SNP rs2523393, which we have previously shown is an eQTL for the HLA-F gene and significantly associated with fecundability (time to pregnancy). We replicated the association between rs2523393 genotype and HLA-F expression using GTEx data and demonstrate that HLA-F is up-regulated in the endometrium during the window of implantation and by progesterone in decidual stromal cells. Next, we show that the rs2523393 A allele creates a new GATA2 binding site in a progesterone responsive distal enhancer that loops to the HLA-F promoter. Remarkably, we found that the A allele is derived in the human lineage, that G/A polymorphism arose before the divergence of modern and archaic humans, and is segregating at intermediate to high frequencies across human populations. Remarkably, the derived A is also has been identified in a GWAS as a risk allele for multiple sclerosis. These data suggests that the polymorphism is maintained by antagonistic pleiotropy and a reproduction-health tradeoff in human evolution.

2.P.308 Lipoprotein(a), apolipoprotein E and hormonal profile in menstruating women after myocardial infarction

1997 ◽  
Vol 134 (1-2) ◽  
pp. 180-181
Author(s):  
A. Jasińska ◽  
U. Ablewska ◽  
D. Liszewska-Pfeifer ◽  
D. Bobdewicz ◽  
M. Faryna ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Apolipoprotein E ◽  
Hormonal Profile ◽  
Lipoprotein A ◽  
Menstruating Women

Abstract 67: miR-19 Deficiency Impairs Cardiac Repolarization in Zebrafish

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Alexander Benz ◽  
Hugo A Katus ◽  
David Hassel
Keyword(s):  
Long Qt Syndrome ◽  
Heart Function ◽  
Cardiac Contractility ◽  
Potential Candidate ◽  
Long Qt ◽  
Vast Number ◽  
Small Noncoding Rnas ◽  
Potential Candidate Gene ◽  
Increased Sensitivity ◽  
Qt Syndrome

The most common outcome of heart failure (HF) is sudden cardiac death which results mostly from prolonged action potential duration (APD) and arrhythmias. During the pathogenesis and progression of HF, a vast number of signaling pathways are altered. microRNAs are small noncoding RNAs that post-transcriptionally finetune gene expression. Interestingly, several microRNAs are dysregulated during HF, suggesting a potential involvement in the development and progression of the disease. Here, we identified miR-19 as an important regulator of heart function. Zebrafish lacking miR-19 developed severe bradycardia and reduced cardiac contractility. While the mammalian genome encodes for two isoforms of miR-19, zebrafish express four members (19a-d). We found that the reduction of miR-19b specifically is sufficient to cause bradycardia and reduced cardiac contractility. Imaging of ventricular APs from whole hearts revealed that APD is significantly prolonged and repolarization is impaired in miR-19b deficient zebrafish. By qRT-PCR experiments we showed that the expression of several cardiac ion channels is altered. Moreover, miR-19b deficiency results in increased sensitivity to an AV-Block, which is a characteristic feature of long QT-Syndrome in zebrafish. In conclusion, we identified miR-19b as a novel and essential modulator of the electrical activity of the heart and establish miR-19b as a potential candidate gene causative for human long QT syndrome.

scholarly journals Clinical, Immunological, and Functional Characterization of Six Patients with Very High IgM Levels

2020 ◽  
Vol 9 (3) ◽  
pp. 818 ◽  
Author(s):  
Vera Gallo ◽  
Emilia Cirillo ◽  
Rosaria Prencipe ◽  
Alessio Lepore ◽  
Luigi Del Vecchio ◽  
...  
Keyword(s):  
B Cell ◽  
Somatic Hypermutation ◽  
Functional Characterization ◽  
Class Switch Recombination ◽  
Pathogenic Mutation ◽  
Potential Candidate ◽  
Class Switch ◽  
Potential Candidate Gene ◽  
Very High

Very high IgM levels represent the hallmark of hyper IgM (HIGM) syndromes, a group of primary immunodeficiencies (PIDs) characterized by susceptibility to infections and malignancies. Other PIDs not fulfilling the diagnostic criteria for HIGM syndromes can also be characterized by high IgM levels and susceptibility to malignancies. The aim of this study is to characterize clinical phenotype, immune impairment, and pathogenic mechanism in six patients with very high IgM levels in whom classical HIGM syndromes were ruled out. The immunological analysis included extended B-cell immunophenotyping, evaluation of class switch recombination and somatic hypermutation, and next generation sequencing (NGS). Recurrent or severe infections and chronic lung changes at the diagnosis were reported in five out of six and two out of six patients, respectively. Five out of six patients showed signs of lymphoproliferation and four patients developed malignancies. Four patients showed impaired B-cell homeostasis. Class switch recombination was functional in vivo in all patients. NGS revealed, in one case, a pathogenic mutation in PIK3R1. In a second case, the ITPKB gene, implicated in B- and T-cell development, survival, and activity was identified as a potential candidate gene. Independent of the genetic basis, very high IgM levels represent a risk factor for the development of recurrent infections leading to chronic lung changes, lymphoproliferation, and high risk of malignancies.

scholarly journals Systematic Analysis and Functional Validation of Citrus Pectin Acetylesterases (CsPAEs) Reveals that CsPAE2 Negatively Regulates Citrus Bacterial Canker Development

2020 ◽  
Vol 21 (24) ◽  
pp. 9429
Author(s):  
Qiang Li ◽  
Jia Fu ◽  
Xiujuan Qin ◽  
Wen Yang ◽  
Jingjing Qi ◽  
...  
Keyword(s):  
Susceptible Variety ◽  
Resistant Variety ◽  
Potential Candidate ◽  
Bacterial Canker ◽  
Citrus Pectin ◽  
Systematic Analysis ◽  
Canker Disease ◽  
Potential Candidate Gene ◽  
Citrus Bacterial Canker ◽  
Canker Development

The present study was designed to serve as a comprehensive analysis of Citrus sinensis (C. sinensis) pectin acetylesterases (CsPAEs), and to assess the roles of these PAEs involved in the development of citrus bacterial canker (CBC) caused by Xanthomonas citri subsp. citri (Xcc) infection. A total of six CsPAEs were identified in the genome of C. sinensis, with these genes being unevenly distributed across chromosomes 3, 6, and 9, and the unassembled scaffolds. A subset of CsPAEs were found to be involved in responses to Xcc infection. In particular, CsPAE2 was identified to be associated with such infections, as it was upregulated in CBC-susceptible variety Wanjincheng and inversely in CBC-resistant variety Calamondin. Transgenic citrus plants overexpressing CsPAE2 were found to be more susceptible to CBC, whereas the silencing of this gene was sufficient to confer CBC resistance. Together, these findings provide evolutionary insights into and functional information about the CsPAE family. This study also suggests that CsPAE2 is a potential candidate gene that negatively contributes to bacterial canker disease and can be used to breed CBC-resistant citrus plants.

scholarly journals Over-expression of poplar NAC15 gene enhances wood formation in transgenic tobacco

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wenjing Yao ◽  
Dawei Zhang ◽  
Boru Zhou ◽  
Jianping Wang ◽  
Renhua Li ◽  
...  
Keyword(s):  
Transgenic Tobacco ◽  
Wood Formation ◽  
Potential Candidate ◽  
Rna Seq ◽  
Populus Simonii ◽  
Over Expression ◽  
Potential Candidate Gene ◽  
Relative Expression Level ◽  
Transgenic Lines ◽  
Highly Expressed Genes

Abstract Background NAC (NAM/ATAF/CUC) is one of the largest plant-specific transcription factor (TF) families known to play significant roles in wood formation. Acting as master gene regulators, a few NAC genes can activate secondary wall biosynthesis during wood formation in woody plants. Results In the present study, firstly, we screened 110 differentially expressed NAC genes in the leaves, stems, and roots of di-haploid Populus simonii×P. nigra by RNA-Seq. Then we identified a nucleus-targeted gene, NAC15 gene, which was one of the highly expressed genes in the stem among 110 NAC family members. Thirdly, we conducted expression pattern analysis of NAC15 gene, and observed NAC15 gene was most highly expressed in the xylem by RT-qPCR. Moreover, we transferred NAC15 gene into tobacco and obtained 12 transgenic lines overexpressing NAC15 gene (TLs). And the relative higher content of hemicellulose, cellulose and lignin was observed in the TLs compared to the control lines containing empty vector (CLs). It also showed darker staining in the culms of the TLs with phloroglucinol staining, compared to the CLs. Furthermore, the relative expression level of a few lignin- and cellulose-related genes was significantly higher in the TLs than that in the CLs. Conclusions The overall results indicated that NAC15 gene is highly expressed in the xylem of poplar and may be a potential candidate gene playing an important role in wood formation in transgenic tobacco.

Association analyses of depression and genes in the hypothalamus–pituitary–adrenal axis

2016 ◽  
Vol 29 (1) ◽  
pp. 59-64 ◽  
Author(s):  
Henrietta Nørmølle Buttenschøn ◽  
Jesper Krogh ◽  
Marit Nyholm Nielsen ◽  
Linda Kaerlev ◽  
Merete Nordentoft ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Genetic Variants ◽  
Stressful Life Events ◽  
Potential Candidate ◽  
Nucleotide Polymorphisms ◽  
Gene Encoding ◽  
Single Nucleotide ◽  
Association Analyses ◽  
Potential Candidate Gene ◽  
Potential Association

ObjectiveDysregulation of the hypothalamic–pituitary–adrenal (HPA) axis has been reported in depression. The aim was to investigate the potential association between depression and seven genes regulating or interfering with the HPA axis, including the gene encoding angiotensin converting enzyme (ACE).MethodsIn total, 78 single nucleotide polymorphisms (SNPs) and one insertion/deletion polymorphism were genotyped. The study included 408 individuals with depression and 289 controls. In a subset of cases, the interaction between genetic variants and stressful life events (SLEs) was investigated.ResultsAfter quality control, 68 genetic variants were left for analyses. Four of nine variants within ACE were nominally associated with depression and a gene-wise association was likewise observed. However, none of the SNPs located within AVP, CRH, CRHR1, CRHR2, FKBP5 or NC3C1 were associated with depression. One nominally significant interaction, most likely due to chance, was identified.ConclusionThe results indicate that ACE could be a potential candidate gene for depression.

A new case of rare proximal 3q13 interstitial deletion

Open Medicine ◽  
2011 ◽  
Vol 6 (5) ◽  
pp. 625-630 ◽  
Author(s):  
Luca Lovrecic ◽  
Gorazd Rudolf ◽  
Alenka Veble ◽  
Borut Peterlin
Keyword(s):  
Pyramidal Neurons ◽  
Clinical Symptoms ◽  
Interstitial Deletion ◽  
Lower Limbs ◽  
Psychomotor Development ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Potential Candidate ◽  
Potential Candidate Gene ◽  
Clinical Observations

AbstractWe present the case of a 20-year-old man referred to the clinical geneticist because of mental retardation and dysmorphic features because of concerns about hereditability when his older, healthy brother was expecting a child. Deletion of proximal 3q arm was found with standard G-banding, and array comparative genomic hybridisation (array-CGH) was used to further locate the breakpoints. A unique interstitial deletion del 3q13.11q13.33 was confirmed. The first clinical symptoms in the 20-year-old were described at the age of 4 months when the pediatrician reported muscle hypertonia of the lower limbs, which later evolved into hypotonia. Later clinical observations revealed that the patient’s psychomotor development was delayed: he exhibited craniofacial abnormalities, cryptorchidism, thoracic kyphosis, and tapering fingers. Interstitial deletions of the proximal long arm of chromosome 3 have rarely been reported:; there are only 12 previously reported cases. The breakpoints and sizes of described deletions vary greatly, which makes definite genotype-phenotype conclusions impossible at this time. Developmental delay is one of the common features described in the majority of reported cases. The BTB-zinc finger gene ZBTB20 might be a potential candidate gene: it was shown in the mouse hippocampus to be expressed during the important period of neurogenesis of pyramidal neurons. Also, four of patients reported to date had agenesis of the corpus callosum and one, holoprosencephaly. We suggest that the GAP43 gene is involved in the development of structural neurological abnormalities in patients with 3q deletion.

Trascriptome Analysis of Bone Marrow CD14+ Monocytes Revealed Differential Expression Profiles in Symptomatic Multiple Myeloma (MM) Compared to Smoldering MM and Monoclonal Gammopathy of Undetermined Significance

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1811-1811
Author(s):  
Marco Peronaci ◽  
Paola Storti ◽  
Domenica Ronchetti ◽  
Luca Agnelli ◽  
Marina Bolzoni ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Differentially Expressed Genes ◽  
Monoclonal Gammopathy ◽  
Conflicts Of Interest ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Potential Candidate ◽  
Molecular Alterations ◽  
Potential Candidate Gene

Abstract Abstract 1811 Symptomatic multiple myeloma (MM), smoldering MM (SMM) and monoclonal gammopathy of uncertain significance (MGUS) are well known different pathological and clinical entities of plasma cell (PC) disorders. Nevertheless molecular studies performed on clonal CD138+ PC do not clear distinguished these disorders that share common alterations. Studies focusing on the presence of potential molecular alterations in the microenvironment cells are ongoing. Because monocytes are the cells primarily involved in osteoclastogenesis, angiogenesis and immune system disfuction, that are the hallmark of symptomatic MM compared to SMM and MGUS, in this study we have analyzed the transcriptional profile of the bone marrow (BM) CD14+ cells in these settings of patients. BM CD14+ monocytes were purified from a total cohort of 36 patients with PC disorders including 21 patients with symptomatic MM, 8 patients with SMM and 7 patients with MGUS. CD14+ cells were isolated from the CD138 negative fraction of BM samples of patients by immunomagnetic method with anti-CD14 monoclonal antibody conjugated with microbeads. The presence of potential haemopoietic and CD138+ contaminating cells was excluded by FACS analysis. Only samples with CD14 purity greater than 95% were analyzed by microarrays by GeneChip® HG-U133Plus 2.0 arrays (Affymetrix®) (13 MM, 8 SMM and 7 MGUS). Data obtained were then validated on selected genes by Real-Time quantitative PCR. A multiclass analysis identified 14 differentially expressed genes, which characterized MGUS vs SMM vs symptomatic MM. A supervised analysis between symptomatic MM vs. SMM and MGUS samples identified 101 genes differentially expressed in CD14+ (58 genes up-regulated in MM vs SMM and MGUS and 43 genes donwregulated). Interestingly, among the differentially expressed genes we found that cytokines and cytokine receptors (IL21, IL21R, IL15, IL15R), chemokines (CXCL10, CXCL11) and interferon-inducible proteins (IFI27, IFI44) were up-regulated in CD14+ of MM patients as compared to SMM and MGUS. A supervised analysis between MM and MGUS identified 6 differentially expressed genes in CD14+ whereas 37 genes distinguished MM and SMM patients. Notably the SLAMF7 (CS1) gene recently indentified as a therapeutic target in CD138+ MM cells was up-regulated in CD14+ monocytes of MM patients as compared either to MGUS alone or to MGUS plus SMM could be a potential candidate gene. Overall our preliminary results indicate that a different transcriptional fingerprint may be identified in BM CD14+ cells of patients with symptomatic MM as compared to those with indolent PC disorders such as SMM and MGUS with a greater number of differentially expressed genes between symptomatic MM and SMM patient rather than between MM and MGUS. Disclosures: No relevant conflicts of interest to declare.

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