3972 results for "*geneti*"

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• Identification of the cause of juvenile parkinsonism in a case_SYNJ1

  This study aimed to elucidate the genetic causes underlying the Juvenile Parkinsonism diagnosed in a girl using whole-exome sequencing, analysis of CAG repeats, RNA sequencing analysis on fibroblasts, and metabolite identification. As a result, a homozygous missense mutation SNP T/C (rs2254562) in SYNJ1 and alteration in metabolism were identified.

  Study EGAS00001007686

• Regulatory Elements active in Insulinomas

  Characterization of regulatory elements active insulinomas, assessed by the presence of H3K27ac. This study also includes characterization of H3K27me3 in control pancreatic beta cells.

  Study EGAS50000000319

• Whole-exome sequencing of acute myeloid leukemias with aberrations of chromosome 7

  Deletions and partial losses of chromosome 7 are frequent in acute myeloid leukemia (AML) and are often linked to dismal outcome. However, the genomic landscape and prognostic impact of concomitant genetic aberrations remain incompletely understood. Therefore, we performed whole-exome sequencing of acute myeloid leukemias (N = 60) with aberrations of chromosome 7.

  Study EGAS50000000429

• Epigenetic memory of SARS-CoV-2 mRNA vaccination in monocyte-derived macrophages

  Immune memory is key to effective antimicrobial responses, but the impact of mRNA vaccines on this process is not fully understood. Our research shows that SARS-CoV-2 mRNA vaccines alter the epigenetic profile of human macrophages, specifically enhancing histone acetylation, which is linked to immune training. Significant epigenetic changes, along with increased cytokine release, require two vaccine doses. However, these effects diminish over time but can be restored with a booster dose six months later, maintaining a strong pro-inflammatory response.

  Study EGAS50000000341

• Decoding Human Endogenous Retrovirus Expression in Liver Metastatic Colorectal Cancers: Implications for Diagnosis and Prognosis

  The association between Human Endogenous RetroVirus (HERV) expression and cancer can be considered to both reflect the epigenetic deregulation of cancer and facilitate oncogenesis through its promoter/enhancer action on genes. More than 50% of colorectal cancers develop liver metastases and HERV has never been studied in this setting. We collected 400 RNAseq samples from more than 200 patients with primary and liver metastases from published and unpublished databases. We corroborated our findings with tandem mass spectrometry from primary colorectal cancer and single-cell RNAseq from liver metastatic colorectal cancer (lmCRC). We identified global stability in HERV expression between liver metastases and primary colorectal cancers, suggesting an early oncogenic footprint. Therefore, we proposed a list of seventeen HERV loci for lmCRC characterization with ERV-derived peptides but no expression in normal tissues. Among them, we discovered six prognostic markers after surgical resection of lmCRC. Four of them, HERVH_Xp22.32a, HERVH_20p11.23b, HERVH_13q33.3, HERVH_13q31.3, showed poor prognostic value when expressed (log-rank p-value 0.028, 0.0083, 9e-4, 0.05, respectively). HERVH_Xp22.2c (log-rank p-value 0.032) and HERVH_8q21.3b (only in multivariate models) were associated with better prognosis when expressed. These markers showed a cumulative effect on survival when expressed. Some HERVs were associated with decreased cytotoxic immune cells and most of them correlated with cell cycle pathways. Our findings provide new insights into lmCRC classification and suggest novel prognostic biomarkers and potential therapeutic targets.

  Study EGAS50000000307

• Targeted sequencing of genomic regions of interest in depression and obesity

  This study aimed to further explore the genetic relationship between MD and obesity taking advantage of targeted sequencing strategy. Specifically, we searched for genetic risk variants across the entire frequency spectrum in flanking genomic regions and genes previously associated with MD and obesity, assessed the contribution of those variants to the pathophysiology of comorbid MD and obesity, and provided a general overview of the cellular and molecular pathways mapped by those variants when these complex diseases co-occur.

  Study EGAS50000000330

• Circulating tumor cells for comprehensive and multiregional non-invasive genetic characterization of multiple myeloma

  Study EGAS00001004288

• Toxigenic Clostridium perfringens isolated from at-risk pediatric inflammatory bowel disease patients

  With the goal of studying mucosal-associated bacteria and products detrimental to inflammatory bowel disease (IBD) patients, we directly cultured bacterial communities from mucosal biopsies and examined for detrimental traits. Focusing on red blood cell lysis, a virulence trait, communities from 5 of 9 patients exhibited hemolytic activity. Clostridium perfringens was isolated from each hemolytic community, and whole-genome sequencing confirmed presence of hemolytic toxins – alpha toxin in all 5 strains, perfringolysin O (PFO) in 4 strains, alveolysin in 2 strains – and absence of enterotoxins. In vitro cytotoxicity experiments demonstrated strain supernatants were toxic to various cell types located beneath the intestinal epithelial barrier, including endothelial, neuroblasts, and neutrophils, while impact on epithelial cells was less pronounced. These findings suggest C. perfringens may be damaging particularly when intestinal barrier integrity is compromised, such as in IBD patients. Further characterization using purified toxins and genetic insertion mutants confirmed PFO toxin was sufficient for cell toxicity. C. perfringens supernatants also induced activation of neuroblast and dorsal root ganglion (DRG) neuron cells in vitro, suggesting C. perfringens in inflamed mucosal tissue may directly contribute to abdominal pain, a frequent IBD symptom. Strikingly, C. perfringens was detected in biopsies of 8 of 9 pediatric patients while not in all corresponding stool samples, and in other datasets, C. perfringens was in stool samples of IBD adults (18.7-27.1%) much more frequently versus healthy (5.1%). Our findings showcase C. perfringens may have an important pathogenic impact on IBD patients. Similar to Clostridioides difficile, routine monitoring of C. perfringens and PFO toxins in patients may be beneficial.

  Study EGAS50000000334

• Primary central nervous system lymphoma (PCNSL) biopsies show heterogeneity in gene expression profiles, genetic subtypes, and in vitro drug sensitivity to kinase inhibitors

  Primary central nervous system lymphoma (PCNSL) is an aggressive large B-cell lymphoma, most often of the activated B cell (ABC) subtype, but with limited tumor biology studies due to small biopsy size and lack of strict cohort definition. Here we examined the genetic heterogeneity of 29 HIV- EBV- PCNSL tumors using whole exome sequencing (WES). We compared these tumors to 5 cell lines comprised of two human PCNSL cell lines (TK and HKBML) and three systemic activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) (OCI-Ly3, TMD-8, HBL-1).

  Study EGAS50000000312

• Targeting Heterochromatin Eliminates Malignant Stem Cells in Chronic Myelomonocytic Leukemia Through Reactivation of Retroelements and Innate Immune pathways

  Hematopoietic stem cell (HSC) aging involves heterochromatin reorganization. These repressive marks together with DNA methylation are essential for suppressing transposable elements (TEs). In this study we analyze heterochromatin and transcriptomic changes occurring at genes and TEs in HSCs from chronic myelomonocytic leukemia, a severe myeloid malignancy affecting the elderly, compared to age-matched cells, and in the presence or absence of a combination of epidrugs.

  Study EGAS50000000367