Genetic contributions to premenstrual symptoms: revisiting the role of the ESR1 gene

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Abstract Premenstrual dysphoric disorder (PMDD) and its subclinical form categorized as premenstrual syndrome (PMS), are severe mood disorders characterized by cyclical depressive symptoms, anxiety, irritability, other functional impairments, impacting a broad range of women during the late luteal phase. The estrogen receptor 1 ( ESR1) gene encodes alpha (ERα) which plays critical role in mediating signaling regulates various physiological psychological processes. In this study, we investigated relationship between six single nucleotide polymorphisms (SNPs) intron 4 ESR1 symptom severity, emphasizing symptom- genotype associations SNP interactions. Results demonstrated that specific SNPs were linked to distinct profiles, such difficulty concentrating, sleep disturbances. Interactions revealed both risk-enhancing protective effects. These findings suggest symptoms may stem from genotype-linked reduced sensitivity ovarian hormones, providing foundation for future research.

Язык: Английский

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Triplex H-DNA Structure: The Long and Winding Road from the Discovery to Its Role in Human Disease

Deleted Journal, Год журнала: 2024, Номер unknown

Опубликована: Дек. 5, 2024

Abstract H-DNA is an intramolecular DNA triplex formed by homopurine-homopyrimidine mirror repeats. Since its discovery, the field has advanced from characterizing structure in vitro to discovering existence and role vivo. interacts with cellular machinery unique ways, stalling RNA polymerases causing genome. The foundational S1 nuclease chemical probing technologies originally used show formation have been updated combined genome-wide sequencing methods for large-scale mapping of secondary structures. There evidence H-DNA’s polycystic kidney disease, cancer, numerous repeat expansion diseases. In disease (PKD), forming region within PKD1 gene stalls replication induces fragility. H-DNA- repeats various genes a cancer; most well-studied examples involve H-DNA-mediated fragility translocations multiple lymphomas. Lastly, H-DNA-forming implicated four diseases: Friedreich's ataxia (FRDA), GAA-FGF14-related ataxia, X-linked Dystonia Parkinsonism (XDP), cerebellar neuropathy vestibular areflexia syndrome (CANVAS). this review, we summarize discovery characterization, function vivo, field's current knowledge on physiology pathology.

Язык: Английский

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G-quadruplex forming regions in GCK and TM6SF2 are targets for differential DNA methylation in metabolic disease and hepatocellular carcinoma patients

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Авг. 30, 2024

The alarming increase in global rates of metabolic diseases (MetDs) and their association with cancer risk renders them a considerable burden on our society. interplay environmental genetic factors causing MetDs may be reflected DNA methylation patterns, particularly at non-canonical (non-B) structures, such as G-quadruplexes (G4s) or R-loops. To gain insight into the mechanisms MetD progression, we focused functional analyses intragenic regions two genes, glucokinase (GCK) exon 7 transmembrane 6 superfamily 2 (TM6SF2) intron 2-exon 3 boundary, which harbor non-B motifs for G4s R-loops.Pyrosequencing 148 blood samples from nested cohort study revealed significant differential GCK TM6SF2 patients versus healthy controls. Furthermore, these hypervariable differentially methylated CpGs also hepatocellular carcinoma normal tissue Cancer Genome Atlas (TCGA). Permanganate/S1 nuclease footprinting direct adapter ligation (PDAL-Seq), native polyacrylamide gel electrophoresis circular dichroism (CD) spectroscopy formation G4 structures demonstrated that topology stability is affected by methylation. Detailed including histone marks, chromatin conformation capture data, luciferase reporter assays, highlighted cell-type specific regulatory function target regions. Based analyses, hypothesize changes lead to topological changes, especially 7, cause activation alternative elements potentially play role splicing.Our provide new view underlying progression link carcinomas, unveiling important key players already early disease stages.

Язык: Английский

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Evolutionary Dynamics of G-Quadruplexes in Human and Other Great Ape Telomere-to-Telomere Genomes

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

ABSTRACT G-quadruplexes (G4s) are non-canonical DNA structures that can form at approximately 1% of the human genome. G4s contribute to point mutations and structural variation thus facilitate genomic instability. They play important roles in regulating replication, transcription, telomere maintenance, some them evolve under purifying selection. Nevertheless, evolutionary dynamics has remained underexplored. Here we conducted a comprehensive analysis predicted (pG4s) recently released, telomere-to-telomere (T2T) genomes other great apes—bonobo, chimpanzee, gorilla, Bornean orangutan, Sumatran orangutan. We annotated tens thousands new pG4s T2T compared previous ape genome assemblies, including 41,236 Analyzing species alignments, found one-third shared by all apes studied identified species– genus-specific pG4s. accumulated diverged rates consistent with divergence times between species. observed significant enrichment hypomethylation pG4 across regulatory regions, promoters, 5’ 3’UTRs, origins strongly suggesting their formation functional role these regions. among displayed lower methylation levels species-specific pG4s, conservation former. Many were located repetitive satellite regions deciphered genomes. Our findings illuminate G4s, gene regulation, potential contribution adaptations apes, emphasizing utility high-resolution uncovering previously elusive features.

Язык: Английский

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G-quadruplex formation in GCK and TM6SF2 are targets for differential DNA methylation in metabolic dysfunction-associated fatty liver disease and type II diabetes mellitus patients

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 26, 2024

The alarming increase in global rates of metabolic diseases (MetDs) and their association with cancer risk renders them a considerable burden on our society. interplay environmental genetic factors causing MetDs may be reflected DNA methylation patterns, particularly at non-canonical (non-B) structures, such as G-quadruplexes (G4s) or R-loops. To gain insight into the mechanisms MetD progression, we focused functional analyses intragenic regions two genes, glucokinase (GCK) exon 7 transmembrane 6 superfamily 2 (TM6SF2) intron 2-exon 3 boundary, which harbor non-B motifs for G4s Pyrosequencing 148 blood samples from nested cohort study revealed significant differential GCK TM6SF2 patients versus healthy controls. Furthermore, these hypervariable differentially methylated CpGs also hepatocellular carcinoma normal tissue Cancer Genome Atlas (TCGA). Permanganate/S1 nuclease footprinting direct adapter ligation (PDAL-Seq), native polyacrylamide gel electrophoresis circular dichroism (CD) spectroscopy formation G4 structures demonstrated that topology stability is affected by methylation. Detailed including histone marks, chromatin conformation capture data, luciferase reporter assays, highlighted cell-type specific regulatory function target regions. Based analyses, hypothesize changes lead to topological changes, especially 7, cause activation alternative elements potentially play role splicing. Our provide new view underlying progression link carcinomas, unveiling important key players already early disease stages.

Язык: Английский

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Unraveling the complexity: Advanced methods in analyzing DNA, RNA, and protein interactions

Advances in cancer research, Год журнала: 2024, Номер unknown, С. 251 - 302

Опубликована: Янв. 1, 2024

Язык: Английский

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