Journal of translational genetics and genomics最新文献

{"title":"Epigenetic effects of high-fat diet on intestinal tumorigenesis in C57BL/6J-<i>Apc</i> ^<i>Min</i>/+ mice.","authors":"Dan C Qu,&nbsp;Devin Neu,&nbsp;Zain Q Khawaja,&nbsp;Ruoyu Wang,&nbsp;Cynthia F Bartels,&nbsp;Katreya Lovrenert,&nbsp;Ernest R Chan,&nbsp;Anne E Hill-Baskin,&nbsp;Peter C Scacheri,&nbsp;Nathan A Berger","doi":"10.20517/jtgg.2022.16","DOIUrl":"https://doi.org/10.20517/jtgg.2022.16","url":null,"abstract":"<p><strong>Aim: </strong>Obesity and obesogenic diets might partly accelerate cancer development through epigenetic mechanisms. To determine these early effects, we investigated the impact of three days of a high-fat diet on epigenomic and transcriptomic changes in <i>Apc</i> ^<i>Min</i>/+ murine intestinal epithelia.</p><p><strong>Method: </strong>ChIP-Seq and RNA-Seq were performed on small intestinal epithelia of WT and <i>Apc</i> ^<i>Min</i>/+ male mice fed high-fat diet (HFD) or low-fat diet (LFD) for three days to identify genomic regions associated with differential H3K27ac levels as a marker of variant enhancer loci (VELs) as well as differentially expressed genes (DEGs).</p><p><strong>Results: </strong>Regarding epigenetic and transcriptomic changes, diet type (LFD <i>vs</i>. HFD) showed a significant impact, and genotype (WT <i>vs</i>.<i>Apc</i> ^<i>Min</i>/+) showed a small impact. Compared to LFD, HFD resulted in 1306 gained VELs, 230 lost VELs, 133 upregulated genes, and 127 downregulated genes in WT mice, with 1056 gained VELs, 371 lost VELs, 222 upregulated genes, and 182 downregulated genes in <i>Apc</i> ^<i>Min</i>/+ mice. Compared to the WT genotype, the <i>Apc</i> ^<i>Min</i>/+ genotype resulted in zero changed VELs for either diet type group, 21 DEGs for LFD, and 48 DEGs for HFD. Most gained VELs, and upregulated genes were associated with lipid metabolic processes. Gained VELs were also associated with Wnt signaling. Downregulated genes were associated with antigen presentation and processing.</p><p><strong>Conclusion: </strong>Three days of HFD-induced epigenomic and transcriptomic changes involving metabolic and immunologic pathways that may promote tumor growth in the genetically predisposed murine intestine without affecting key cancer signaling pathways.</p>","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9937564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10797190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomics in practice - a review of inherited cardiac conditions","authors":"","doi":"10.20517/jtgg.2022.20","DOIUrl":"https://doi.org/10.20517/jtgg.2022.20","url":null,"abstract":"","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local causal pathway discovery for single-cell RNA sequencing count data: a benchmark study","authors":"","doi":"10.20517/jtgg.2022.22","DOIUrl":"https://doi.org/10.20517/jtgg.2022.22","url":null,"abstract":"","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms regulating mitochondrial DNA quality control","authors":"Nitish Dua, Anjana Badrinarayanan","doi":"10.20517/jtgg.2023.0","DOIUrl":"https://doi.org/10.20517/jtgg.2023.0","url":null,"abstract":"Maintenance of genome integrity is essential for cellular survival. There are mechanisms utilized by the cells to sense and respond to assaults on genomic DNA. These mechanisms are conserved across all domains of life and are collectively called the DNA damage response pathways. However, eukaryotic cells also have extrachromosomal DNA in mitochondria (mtDNA), which is indispensable for mitochondrial function, and hence cell survival. Indeed, impaired mitochondrial activity arising due to mutations in mtDNA has been found to be associated with many human pathologies. Despite its importance, our understanding of how cells ensure mtDNA genome integrity is limited. Since mitochondria do not encode for machinery required for the maintenance of their own genomes, they depend on the nucleus for replication, transcription, and repair processes. This adds a layer of complexity with the requirement for organelle crosstalk and coordination in response to mtDNA damage. This review summarizes recent findings that provide new insights into mechanisms involved in mtDNA quality control, acting at the level of mtDNA or organelle and also discusses a few new avenues of research towards a comprehensive understanding of the “mtDNA damage response”.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgment to reviewers of Journal of Translational Genetics and Genomics in 2022","authors":"","doi":"10.20517/jtgg.2023.03","DOIUrl":"https://doi.org/10.20517/jtgg.2023.03","url":null,"abstract":"","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenomic screening for agranulocytosis and efficacy with clozapine","authors":"M. Shad","doi":"10.20517/jtgg.2023.11","DOIUrl":"https://doi.org/10.20517/jtgg.2023.11","url":null,"abstract":"Aim: To review genetic biomarkers of agranulocytosis and efficacy with clozapine as a screening tool for the safe and effective use of clozapine. Methods: A PubMed search was performed using PRISMA guidelines for English articles. Separate searches were conducted using “clozapine” AND “agranulocytosis,” and “clozapine” AND (“response” OR efficacy “outcome”) AND “schizophrenia”. Eligible studies reported positive findings with genetic polymorphism(s) associated with clozapine-induced agranulocytosis (CIA) and clozapine’s efficacy. Case reports/series, abstracts, systematic reviews, and meta-analyses were excluded. Negative and genome-wide studies were not formally reviewed but included in the discussion. Results: Twelve out of 572 CIA studies and 32 out of 126 efficacy studies met the eligibility criteria for this review. Most reviewed studies were conducted in small samples of Jewish, Caucasian, and Asian populations using a candidate gene approach. Conclusion: Future research needs to address the limitations of the findings from the reviewed studies to enable a combined genetic screening for CIA and clozapine response to optimize the safe and effective use of clozapine without unnecessarily exposing potential clozapine nonresponders to CIA or neutropenia.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish models of inherited retinal dystrophies","authors":"B. Perkins","doi":"10.20517/jtgg.2021.47","DOIUrl":"https://doi.org/10.20517/jtgg.2021.47","url":null,"abstract":"Inherited retinal degenerations (IRDs) cause permanent vision impairment or vision loss due to the death of rod and cone photoreceptors. Animal models of IRDs have been instrumental in providing knowledge of the pathological mechanisms that cause photoreceptor death and in developing successful approaches that could slow or prevent vision loss. Zebrafish models of IRDs represent an ideal model system to study IRDs in a cone-rich retina and to test strategies that exploit the natural ability to regenerate damaged neurons. This review highlights those zebrafish mutants and transgenic lines that exhibit adult-onset retinal degeneration and serve as models of retinitis pigmentosa, cone-rod dystrophy, and ciliopathies.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48468483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of molecular signatures and pathways of obese breast cancer gene expression data by a machine learning algorithm","authors":"Betul Comertpay, E. Gov","doi":"10.20517/jtgg.2021.44","DOIUrl":"https://doi.org/10.20517/jtgg.2021.44","url":null,"abstract":"Aim: Currently, the obesity epidemic is one of the biggest problems for human health. Obesity is impacted on survival in patients with breast cancer. However, key biomarkers of obesity-related breast cancer risk are still not well known. Thus, using machine learning to identify the most appropriate features in obesity-associated breast cancer patients may improve the predictive accuracy and interpretability of regression models. Methods: In the present study, we identified 23 differentially expressed genes (DEGs) from the GSE24185 transcriptome dataset. Seed genes were identified from DEGs, the co-expression network genes and hub genes of the protein-protein interaction network. Pathway enrichment analysis was performed for DEGs. The Ridge penalty regression model was executed by using P-values of enriched pathways and seed gene pathway association score to obtain the most relevant molecular signatures. The model was performed using 10-fold cross-validation to fit the penalized models. Results: Angiotensin II receptor type 1 (AGTR1), cyclin D1 (CCND1), glutamate ionotropic receptor AMPA type subunit 2 (GRIA2), interleukin-6 cytokine family signal transducer (IL6ST), matrix metallopeptidase 9 (MMP9), and protein kinase CAMP-dependent type II regulatory subunit beta (PRKAR2B) were considered as candidate molecular signatures of obese patients with breast cancer. In addition, RAF-independent MAPK1/3 activation, collagen degradation, bladder cancer, drug metabolism-cytochrome P450, and signaling by Hedgehog pathways in cancer were primarily associated with obesity-associated breast cancer. Conclusion: These genes may be used for risk analysis of the disease progression of obese patients with breast cancer. Corresponding genes and pathways should be validated via experimental studies.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen and DNA damage modulate mRNA levels of genes involved in homologous recombination repair in estrogen-deprived cells","authors":"L. Zach, Lia Yedidia-Aryeh, M. Goldberg","doi":"10.20517/jtgg.2021.58","DOIUrl":"https://doi.org/10.20517/jtgg.2021.58","url":null,"abstract":"Aims: Breast and ovarian cancers are frequently associated with mutations in genes involved in DNA double-strand break (DSB) repair by homologous recombination (HR). Risk factors for breast cancer are often linked to estrogen-related pathways. Here, we studied the crosslink between estrogen and the HR pathway. Methods: We analyzed, using online annotation tolls, the enrichment of candidate estrogen-upregulated genes among DNA repair pathways. We analyzed how estrogen modulates mRNA levels of HR repair (HRR) genes in estrogen-receptor (ER)-positive cells. The cells were deprived of estrogen, and the mRNA levels of HRR genes were determined using real-time polymerase chain reaction, following estrogen addition as well as DNA damage induction. In addition, we examined the effect of estrogen on DNA repair, by immuno-fluorescence analysis, using the DSB marker phospho-histone H2AX, as an indicator for DSB repair. Finally, we performed a clonogenic survival assay to determine the effect of estrogen on cell survival. Results: We discovered that genes whose mRNA levels are upregulated by estrogen are strongly associated with the HR pathway. We validated that estrogen upregulates mRNA levels of the HRR genes MRE11, RAD50, and PALB2, which have not been previously shown to be regulated by estrogen. Additionally, we revealed that DNA damage induces an upsurge in mRNAs encoding BRCA1, MRE11, RAD50, PALB2, and CtIP, in ER-positive cells deprived of estrogen. Notably, DSB repair was impaired in ER-positive cells deprived of estrogen, compared to cells exposed to the hormone. We also established that ER-positive cells deprived of estrogen are hypersensitive to DSBs. Conclusion: These results suggest that exposure of ER-positive cells to estrogen triggers the expression of HRR genes, which is required to meet the increased repair demands due to the proliferating effect induced by estrogen. This may explain the higher chances of developing estrogen-dependent cancers due to mutations in HRR genes.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NUT midline carcinoma presenting initially as thyroid cancer: a case report and review of treatment","authors":"M. Neumann, Adam M. Hines, Q. Chang, N. Seetharamu, Carlos A. Lopez","doi":"10.20517/jtgg.2022.06","DOIUrl":"https://doi.org/10.20517/jtgg.2022.06","url":null,"abstract":"The purpose of this abstract is to provide data on a 27-year-old woman with a rare and rapidly progressive cancer, Nuclear in Testis (NUT) carcinoma (NC), and to highlight possible treatment options for her specific gene translocation of NSD3-NUT. To our knowledge, this is the first case in the literature that was presented initially as anaplastic thyroid cancer. We propose that targeted therapy with a histone lysine methyltransferase inhibitor may be of benefit as adjunctive therapy in patients with the NSD3-NUT gene translocation.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}