Frontiers in Genetics, Год журнала: 2024, Номер 15
Опубликована: Ноя. 1, 2024
Congenital heart disease (CHD) is the most common birth defect and valve defects are cardiac defect, accounting for over 25% of all congenital diseases. To date, more than 400 genes have been linked to CHD, genetic analysis CHD cases crucial both clinical management etiological determination. Patients with autosomal-recessive variants
Язык: Английский
Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)
Опубликована: Апрель 11, 2024
Abstract The epigenome—the chemical modifications and chromatin-related packaging of the genome—enables same genetic template to be activated or repressed in different cellular settings. This multi-layered mechanism facilitates cell-type specific function by setting local sequence 3D interactive activity level. Gene transcription is further modulated through interplay with factors co-regulators. human body requires this epigenomic apparatus precisely installed throughout development then adequately maintained during lifespan. causal role epigenome pathology, beyond imprinting disorders tumour suppressor genes, was brought into spotlight large-scale sequencing projects identifying that mutations machinery genes could critical drivers both cancer developmental disorders. Abrogation providing new molecular insights pathogenesis. However, deciphering full breadth implications these changes remains challenging. Knowledge accruing regarding disease mechanisms clinical biomarkers, pathogenically relevant surrogate tissue analyses, respectively. Advances include consortia generated reference epigenomes, high-throughput DNA methylome association studies, as well ageing-related diseases from biological ‘clocks’ constructed machine learning algorithms. Also, 3rd-generation beginning disentangle complexity modification haplotypes. Cell-free methylation a biomarker has clear utility potential assess organ damage across many Finally, understanding aetiology brings it opportunity for exact therapeutic alteration CRISPR-activation inhibition.
Язык: Английский
Процитировано
9
Nature Genetics, Год журнала: 2024, Номер 56(11), С. 2517 - 2527
Опубликована: Сен. 16, 2024
Язык: Английский
Процитировано
6
Cancers, Год журнала: 2025, Номер 17(6), С. 982 - 982
Опубликована: Март 14, 2025
Background: Breast cancer (BC), one of the most common cancers, has increased in Mexico during past decade, along with other chronic and metabolic diseases. Methods: Herein, we analyzed 121 SNPs (85 related to BC and/or glucose-associated pathways 36 SNP classified as ancestry markers) 92 confirmed cases 126 unaffected women from Northeastern Mexico. The relationship these BC, considering BMI, menopause status, age cofactors, was explored using a gene–environment (G × E) interaction multi-locus model. Results: Twelve gene variants were significantly associated BC: three located exome (rs3856806 PPARG, rs12792229 MMP8, rs5218 KCNJ11-ABCC8), nine non-coding regions, which are involved accelerated decay mRNA transcripts, regulatory flanking regions (rs3917542 PON1; rs3750804 rs3750805 TCF7L2; rs1121980 rs3751812 FTO; rs12946618 RPTOR; rs2833483 SCAF4; rs11652805 AMZ2P1-GNA13; rs1800955 SCT-DEAF1-DRD4). Conclusions: This study identified an association between menopause, (above 45), obesity, overweight status implicated diabetes mellitus, insulin resistance, inflammation, remodeling extracellular matrix.
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown
Опубликована: Июль 3, 2023
ABSTRACT The rise of large-scale, sequence-based deep neural networks (DNNs) for predicting gene expression has introduced challenges in their evaluation and interpretation. Current evaluations align DNN predictions with experimental perturbation assays, which provides insights into the generalization capabilities within studied loci but offers a limited perspective what drives predictions. Moreover, existing model explainability tools focus mainly on motif analysis, becomes complex when interpreting longer sequences. Here we introduce CREME, an silico toolkit that interrogates large-scale DNNs to uncover rules regulation it learns. Using investigate Enformer, prominent prediction, revealing cis -regulatory elements (CREs) directly enhance or silence target genes. We explore intricate complexity higher-order CRE interactions, relationship between distance from transcription start sites expression, as well biochemical features enhancers silencers learned by Enformer. demonstrate flexibility CREME efficiently higher-resolution view functional sequence CREs. This work demonstrates how can be employed translate powerful study open questions regulation.
Язык: Английский
Процитировано
3
Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
0
Biomedical & Pharmacology Journal, Год журнала: 2024, Номер 17(2), С. 725 - 734
Опубликована: Июнь 25, 2024
In bilaterian animals, axon guidance decisions are regulated by many transmembrane receptor proteins called Roundabout (Robo) family members. During the developmental stages of fruit flies (Drosophila melanogaster), three Robo members play unique roles in central nervous system. Robo3 is revolutionarily conserved among taxa and studies show that regulates mediolateral axonal navigation. Recent suggest guides longitudinal axons a manner independent its ligand (slit). The expression patterns controlled transcription factors (TFs) significant role gene regulation, it not fully understood mechanism. Knowing factor binding sites (TFBS) would help to predict TFs regulate Robo3. this study, bioinformatics tools MEME Suite, TOMTOM, MAST were utilized analyze DNA sequence identify putative assist as docking regions for involved regulation expression. We found seven TFs: Btd, Opa, Mad, Odd, Twi, CF2, h. Mapping these TF motifs against showed located gene. Understanding implement novel strategies control overcome disorders related This study aims unknown may critical
Язык: Английский
Процитировано
0
Frontiers in Genetics, Год журнала: 2024, Номер 15
Опубликована: Ноя. 1, 2024
Congenital heart disease (CHD) is the most common birth defect and valve defects are cardiac defect, accounting for over 25% of all congenital diseases. To date, more than 400 genes have been linked to CHD, genetic analysis CHD cases crucial both clinical management etiological determination. Patients with autosomal-recessive variants
Язык: Английский
Процитировано
0