We are delighted to share you the paper recently published in Medinformatics! The paper is titled "Exploring Disrupted Gene Networks in Human 22q11.2 Microdeletion". It is co-authored by Camila Cristina de Oliveira Alves, Ivan Rodrigo Wolf, and Guilherme Targino Valente from Sao Paulo State University- The Universidade Estadual Paulista (UNESP) and Bruno Faulin Gamba, and Lucilene Arilho Ribeiro Bicudo from Universidade Federal de Goiás. Abstract: Several deletions are observed at the 22q11 locus and are responsible for 22q11.2 deletion syndrome (22q11DS), also known as DiGeorge syndrome, conotruncal anomaly face syndrome, or velocardiofacial syndrome. These microdeletions on human chromosome 22 range from 0.7 to 3 Mb. Many genes are affected by 22q11.2 deletion. However, despite the well-established clinical signs for the diagnosis of 22q11.2 deletion syndrome, the interactome background of 22q11.2 deletion syndrome is unknown. Here, we analyzed protein–protein interaction networks (PPIs) to assess the influences of 3 Mb 22q11.2 deletion on this network. We compared the general human PPI network against a network without 48 genes of the 3 Mb 22q11.2 locus in a homozygous condition: we compared topological metrics, enrichment of gene ontology terms, community assignments, and edge rewiring. The PPI networks revealed that this deletion affected the relevance of hundreds of nondeleted genes. Additionally, this 22q11.2 deletion induces intense rewiring of subnetworks, promoting an accumulation of proteins associated with DiGeorge clinical signs (CTCF, YY1, TFAP2A, PPARG, PAX6, RAX, and E2F3) in a single community (community 1). Therefore, we identified new genes that may be associated with the 22q11.2 deletion syndrome. Altogether, the systemic approaches used here yielded new insights into the 22q11.2 deletion syndrome. To read and share the full paper via the link: https://lnkd.in/gFMZcefM #bioinformatics #medicalresearch #systemsbiology
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In the American Journal of Human Genetics, Daiane Hemerich et al. apply multiple computational methods to prioritize the likely causal gene(s) within more than 500 previously reported GWAS-identified BMI-associated loci. They identified 292 high-scoring genes, most of which have not previously been implicated in obesity. Characterization of these likely causal genes can provide insights into obesity biology. Read the full article here: https://lnkd.in/dQBvwkgQ #ASHG #HumanGenetics
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A novel computational method, multi-region joint detection (MRJD), has emerged as a promising strategy to address the challenges of detecting pathogenic small variants in the PMS2 gene, which is crucial for Lynch syndrome diagnosis. Historically, this task has been complicated by interference from the pseudogene PMS2CL. Integrated into DRAGEN v4.3, MRJD not only supports germline small variant calling in PMS2 but also extends to other repetitive regions in the genome. The human genome is thought to contain upto 500 medically relevant genes where high homology presents significant challenges. MRJD offers a promising solution to these issues. https://lnkd.in/eBtbYD3Z
Overcoming the challenges in PMS2 high-homology regions for improved detection of pathogenic variants associated with Lynch syndrome
illumina.com
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A genomic study has identified a spectrum of overlapping clinical features in disorders affected by the 15q11-q13 region. This region is a genetic locus containing genes subject to genomic imprinting which significantly influences neurodevelopment. Researchers have used Horizon platform for clinical annotations of the genomic variants! These findings established genotype-phenotype correlation for patients affected by structural variations in the 15q11-q13 region. Read here: https://lnkd.in/ddb-Jdi6 #genomics #genomicmedicine #neurodevelopmentaldisorders #precisionmedicine
Expanding deep phenotypic spectrum associated with atypical pathogenic structural variations overlapping 15q11–q13 imprinting region
onlinelibrary.wiley.com
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Genes and cell types in primary open-angle glaucoma Although primary open-angle glaucoma (POAG) is the leading cause of blindness in people over the age of 55, there remains no cure for the disease and its biological mechanisms are not well understood. Elevated intraocular pressure (IOP) is a major risk factor for the disease, but many patients with glaucoma have normal eye pressure and still lose vision. In a new study published in Nature Communications, researchers conducted a comprehensive study that combined genetic discoveries from a large cross-ancestry genome-wide association study meta-analysis of POAG, and a large meta-analysis of IOP with genetic regulation studies and single cell expression measurements in glaucoma-relevant eye tissues. In doing so, they uncovered key genes, biological processes and cell types that may affect the pathogenesis of POAG, in IOP-dependent and independent manners. Using integrative analyses, they identified hundreds of genes and regulatory effects underlying over 100 loci associated with POAG and/or IOP that may contribute to glaucoma risk through altered gene expression levels. These genes are enriched in biological pathways implicated in disease mechanisms, including elastic fiber formation and extracellular matrix organization, vascular development, and neuronal related processes. #ScienceMission #sciencenewshighlights https://lnkd.in/gD3bJNVR
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#2024_Nobel_Prize_Recipients: The Nobel Prize in Physiology or Medicine for 2024 was awarded jointly to Victor Ambros (University of Massachusetts) and Gary Ruvkun (Harvard Medical School) for their groundbreaking work on microRNA and its significant impact on post-transcriptional gene regulation #Discovery_Significance: Their research unveiled a new mechanism of gene regulation that is fundamental for multicellular organisms, demonstrating how cells can selectively activate the correct set of genes necessary for their specific functions, thus enabling diverse cell types to perform specialized roles despite identical genetic information. #Summary: The Nobel Prize in Physiology or Medicine 2024 was awarded to Victor Ambros and Gary Ruvkun for their groundbreaking work in discovering microRNAs and elucidating their roles in post-transcriptional gene regulation. This discovery, rooted in research on the model organism C. elegans, revealed a complex layer of gene regulation that operates in all multicellular life forms. Their work not only identified specific microRNAs like lin-4 and let-7 but also established the importance of these small RNA molecules in controlling developmental timing, cellular identity, and broader physiological processes within organisms. The evolutionary conservation of these regulatory mechanisms underscores their critical functionality, emphasizing the significance of microRNAs in genomic regulation across diverse species. #Engage_Now (Leave your answers in the comments) 1. What are microRNAs, and what functions do they serve in the human body? 2. What animal model was used in the groundbreaking research that led to the discovery of microRNA? Ref: https://lnkd.in/gSb2AFZF
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There is life in the (gene) desert ..! 🏜 New insights into the regulation of a key developmental gene: Researchers at the University of Bern, in collaboration with international partners, have discovered that a section of the genome known as a ‘gene desert’ plays an important role in the development of the embryo and the heart in both mice and humans. The study provides further evidence for the significance of gene-free DNA segments in gene regulation and offers approaches for early detection of cardiac diseases. 🧡 “The present study not only identifies an important non-coding region in the genome, but also shows how complex the mechanisms underlying the regulation of developmental genes are,” says Professor Marco Osterwalder of the Department for BioMedical Research (DBMR) at the Universität Bern and the Department of Cardiology at Insel Gruppe, and leader of the research team that published these results in the journal Nature Communications. ▶ To the Press release: https://lnkd.in/dgfJ_djy The study was supported by the Schweizerischer Nationalfonds SNF. #arrhythmia #precisionmedicine #genemapping #genomics #functionalgenomics
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🧬 A great collaboration with Enza Maria Valente’s (Enza Maria Valente) lab at the Fondazione Mondino - Istituto Neurologico Nazionale IRCCS has shed light on a genetic variant, p.V15A of the SNCA gene, found in a large Italian family, unveiling its critical role in #parkinsondisease (PD). This discovery came from advanced #geneticanalysis and has profound implications for understanding and potentially treating this complex condition. 📑 Published on Movement Disorders journal, find it here: https://lnkd.in/dVWbY35r 📑 👨👩👧👦 The research journey began with the observation of this mutation in five related individuals, linking it directly to PD's characteristic #symptoms such as movement difficulties and cognitive challenges. Interestingly, while three siblings developed PD in their 50s, each case presented unique aspects, highlighting the mutation's diverse impact. 🔬 Delving deeper, we used cutting-edge techniques like #moleculardynamics #simulation and biochemical studies on blood cells to uncover how the mutation affects cellular health. The findings? The mutant protein showed decreased stability and an unstable folded structure. Proband's peripheral blood mononuclear cells showed elevated total and phosphorylated α-synuclein levels and significantly reduced glucocerebrosidase activity. These observations strengthen the connection between α-synuclein accumulation and enzyme dysfunction in PD. 💡 This research not only enhances our understanding of Parkinson's disease at a molecular level but also opens new avenues for targeted #therapies, emphasizing the importance of genetics in unraveling the mysteries of #neurodegenerativediseases. 🌐 Stay tuned for more insights as we continue to explore the #genetic frontiers of health and disease. #bioinformatics #computationalbiology Ospedale Casa Sollievo della Sofferenza
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🧬 Understanding Mitochondrial DNA Depletion Syndrome (MDDS): A Genetic Challenge 🧬 Mitochondrial DNA Depletion Syndrome (MDDS) is a rare genetic disorder marked by a significant reduction in mitochondrial DNA (mtDNA) copy number, leading to severe symptoms such as muscle weakness, neurological deficits, and liver failure. Mutations in the MPV17 gene are a key cause of this syndrome, affecting mtDNA integrity and homeostasis, particularly in high-energy-demand tissues like the liver and brain. Although the exact role of MPV17 remains unclear, ongoing research is focused on elucidating its structural and functional roles using advanced techniques such as TEM, cryo-EM, and NMR. These studies are crucial for better understanding MDDS and identifying potential therapeutic targets. 🔬 #MitochondrialDisease #Genetics #MDDS #MPV17 #Research #Genomics #MolecularBiology #Healthcare #Biotech Check out my blog post https://wix.to/AkQzyyU
Disease-linked inner mitochondrial membrane protein MPV17 - causes MDDS
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⭐🎉 The Nobel prize in Physiology or Medicine 2024 has been awarded jointly to Victor Ambros and Gary Ruvkun for their work on tiny RNA molecules that help cells control which proteins they produce ✨🎉 🎯 This groundbreaking #discovery revealed a completely new principle of gene regulation that turned out to be essential for multicellular organisms, including humans. 🎯 Ambros and Ruvkun were interested in genes that control the timing of activation of different genetic programs, ensuring that various cell types develop at the right time. They studied two mutant strains of worms (C. elegans) lin-4 and lin-14, that displayed defects in the timing of activation of genetic programs during development. These scientists wanted to identify the mutated genes and understand their function. 🎯 Ambros had previously shown that #lin4gene appeared to be a negative regulator of the #lin14gene . However, how the lin-14 activity was blocked was unknown. 🎯 Ambros established the fact that the lin-4 gene produced an unusually short #RNA molecule that lacked a code for protein production. These surprising results suggested that this small RNA from lin-4 was responsible for inhibiting lin-14. 🎯 Concurrently, Ruvkun investigated the regulation of the lin-14 gene and showed that it is not the production of #mRNA from lin-14 that is inhibited by lin-4. The regulation appeared to occur at a later stage in the process of gene expression, through the #shutdown of #protein production. Moreover, there was also a segment in lin-14 mRNA that was necessary for its inhibition by lin-4. 🎯 The two #laureates compared their #findings , which resulted in a breakthrough discovery. 🎯 The short lin-4 #sequence matched #complementary sequences in the critical segment of the lin-14 #mRNA . 🎯 Ambros and Ruvkun performed further experiments showing that the lin-4 #microRNA turns off lin-14 by binding to the complementary sequences in its #mRNA , blocking the production of lin-14 #protein . 🎯 This seminal discovery of #microRNA can deepen our understanding of embryonic developmental, normal cell physiology, and mechanisms underlying cancer progression and neurodegenerative diseases. #NobelPrize #PhysiologyorMedicine #microRNA #posttranscriptionalregulation #geneexpression #proteinproduction
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