Advanced genetics (Hoboken, N.J.)最新文献

{"title":"Indirect Mechanisms of Transcription Factor-Mediated Gene Regulation during Cell Fate Changes","authors":"Michael R. Larcombe,&nbsp;Sheng Hsu,&nbsp;Jose M. Polo,&nbsp;Anja S. Knaupp","doi":"10.1002/ggn2.202200015","DOIUrl":"10.1002/ggn2.202200015","url":null,"abstract":"<p>Transcription factors (TFs) are the master regulators of cellular identity, capable of driving cell fate transitions including differentiations, reprogramming, and transdifferentiations. Pioneer TFs recognize partial motifs exposed on nucleosomal DNA, allowing for TF-mediated activation of repressed chromatin. Moreover, there is evidence suggesting that certain TFs can repress actively expressed genes either directly through interactions with accessible regulatory elements or indirectly through mechanisms that impact the expression, activity, or localization of other regulatory factors. Recent evidence suggests that during reprogramming, the reprogramming TFs initiate opening of chromatin regions rich in somatic TF motifs that are inaccessible in the initial and final cellular states. It is postulated that analogous to a sponge, these transiently accessible regions “soak up” somatic TFs, hence lowering the initial barriers to cell fate changes. This indirect TF-mediated gene regulation event, which is aptly named the “sponge effect,” may play an essential role in the silencing of the somatic transcriptional network during different cellular conversions.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9993476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9455820","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":"Translating Genetic Discovery into a Mechanistic Understanding of Pediatric Movement Disorders: Lessons from Genetic Dystonias and Related Disorders","authors":"Wei-Sheng Lin","doi":"10.1002/ggn2.202200018","DOIUrl":"10.1002/ggn2.202200018","url":null,"abstract":"<p>The era of next-generation sequencing has increased the pace of gene discovery in the field of pediatric movement disorders. Following the identification of novel disease-causing genes, several studies have aimed to link the molecular and clinical aspects of these disorders. This perspective presents the developing stories of several childhood-onset movement disorders, including paroxysmal kinesigenic dyskinesia, myoclonus-dystonia syndrome, and other monogenic dystonias. These stories illustrate how gene discovery helps focus the research efforts of scientists trying to understand the mechanisms of disease. The genetic diagnosis of these clinical syndromes also helps clarify the associated phenotypic spectra and aids the search for additional disease-causing genes. Collectively, the findings of previous studies have led to increased recognition of the role of the cerebellum in the physiology and pathophysiology of motor control—a common theme in many pediatric movement disorders. To fully exploit the genetic information garnered in the clinical and research arenas, it is crucial that corresponding multi-omics analyses and functional studies also be performed at scale. Hopefully, these integrated efforts will provide us with a more comprehensive understanding of the genetic and neurobiological bases of movement disorders in childhood.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.202200018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10350952","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":"Copy Number Variation and Structural Genomic Findings in 116 Cases of Sudden Unexplained Death between 1 and 28 Months of Age","authors":"Catherine A. Brownstein,&nbsp;Elise Douard,&nbsp;Robin L. Haynes,&nbsp;Hyun Yong Koh,&nbsp;Alireza Haghighi,&nbsp;Christine Keywan,&nbsp;Bree Martin,&nbsp;Sanda Alexandrescu,&nbsp;Elisabeth A. Haas,&nbsp;Sara O. Vargas,&nbsp;Monica H. Wojcik,&nbsp;Sébastien Jacquemont,&nbsp;Annapurna H. Poduri,&nbsp;Richard D. Goldstein,&nbsp;Ingrid A. Holm","doi":"10.1002/ggn2.202200012","DOIUrl":"10.1002/ggn2.202200012","url":null,"abstract":"<p>In sudden unexplained death in pediatrics (SUDP) the cause of death is unknown despite an autopsy and investigation. The role of copy number variations (CNVs) in SUDP has not been well-studied. Chromosomal microarray (CMA) data are generated for 116 SUDP cases with age at death between 1 and 28 months. CNVs are classified using the American College of Medical Genetics and Genomics guidelines and CNVs in our cohort are compared to an autism spectrum disorder (ASD) cohort, and to a control cohort. Pathogenic CNVs are identified in 5 of 116 cases (4.3%). Variants of uncertain significance (VUS) favoring pathogenic CNVs are identified in 9 cases (7.8%). Several CNVs are associated with neurodevelopmental phenotypes including seizures, ASD, developmental delay, and schizophrenia. The structural variant 47,XXY is identified in two cases (2/69 boys, 2.9%) not previously diagnosed with Klinefelter syndrome. Pathogenicity scores for deletions are significantly elevated in the SUDP cohort versus controls (<i>p</i> = 0.007) and are not significantly different from the ASD cohort. The finding of pathogenic or VUS favoring pathogenic CNVs, or structural variants, in 12.1% of cases, combined with the observation of higher pathogenicity scores for deletions in SUDP versus controls, suggests that CMA should be included in the genetic evaluation of SUDP.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.202200012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10235350","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":"Reading and writing genomes","authors":"Myles Axton","doi":"10.1002/ggn2.202200027","DOIUrl":"10.1002/ggn2.202200027","url":null,"abstract":"<p><i>Advanced Genetics</i> <b>2020</b>, <i>1</i>, e10016</p><p>https://doi.org/10.1002/ggn2.10016</p><p>The authorship of the above article, first published online on July 29, 2019 in Wiley Online Library (https://doi.org/10.1002/ggn2.10016), is corrected. Alison Liu requested this correction as she did not contribute to this manuscript.</p><p>This correction was agreed between the authors, the Editor-in-Chief, and Wiley Periodicals LLC.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9993468/pdf/GGN2-3-2200027.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9099587","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":"COP27 Climate Change Conference: Urgent Action Needed for Africa and the World","authors":"Lukoye Atwoli,&nbsp;Maha El Adawy,&nbsp;Gregory E. Erhabor,&nbsp;Aiah A. Gbakima,&nbsp;Abraham Haileamlak,&nbsp;Jean-Marie Kayembe Ntumba,&nbsp;James Kigera,&nbsp;Laurie Laybourn-Langton,&nbsp;Fhumulani Mavis Malaudzi,&nbsp;Robert Mash,&nbsp;Joy Muhia,&nbsp;David Ofori-Adjei,&nbsp;Fricay Okonofua,&nbsp;Arash Rashidian,&nbsp;Sahar Yassien Mohammad,&nbsp;Siaka Sidibe,&nbsp;Abdelmadjid Snouber,&nbsp;James Tumwine,&nbsp;Paul Yonga,&nbsp;Lilia Zakhama,&nbsp;Chris Zielinski","doi":"10.1002/ggn2.202200028","DOIUrl":"10.1002/ggn2.202200028","url":null,"abstract":"<p>The 2022 report of the Intergovernmental Panel on Climate Change (IPCC) paints a dark picture of the future of life on earth, characterised by ecosystem collapse, species extinction, and climate hazards such as heatwaves and floods.^[<span>¹</span>^] These are all linked to physical and mental health problems, with direct and indirect consequences of increased morbidity and mortality. To avoid these catastrophic health effects across all regions of the globe, there is broad agreement—as 231 health journals argued together in 2021—that the rise in global temperature must be limited to less than 1.5°C compared with pre-industrial levels.</p><p>While the Paris Agreement of 2015 outlines a global action framework that incorporates providing climate finance to developing countries, this support has yet to materialise.^[<span>²</span>^] COP27 is the fifth Conference of the Parties (COP) to be organised in Africa since its inception in 1995. Ahead of this meeting, we—as health journal editors from across the continent—call for urgent action to ensure it is the COP that finally delivers climate justice for Africa and vulnerable countries. This is essential not just for the health of those countries, but for the health of the whole world.</p><p>In the interest of transparency the authors wish to declare the following roles and relationships: J.K. is the Ex-Officio, President and Secretary of the Kenya Orthopedic Association; J.M. is an unpaid board member of the International Working Group for Health Systems Strengthening; D.O.-A. has a relationship with GLICO Healthcare Ltd.; P.Y. been paid to speak or participate at events by Novartis, bioMerieux and Pfizer; C.Z. is a paid consultant for the UK Health Alliance on Climate Change. The authors declare no further conflicts of interest beyond those inherent in the editorial roles listed above.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9993467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9414648","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":"Liver Metastasis Modulate Responses of Suppressive Macrophages and Exhausted T Cells to Immunotherapy Revealed by Single Cell Sequencing","authors":"Qiming Zhang,&nbsp;Siyuan Liu,&nbsp;Yedan Liu,&nbsp;Dev Bhatt,&nbsp;Juan Estrada,&nbsp;Brian Belmontes,&nbsp;Xianwen Ren,&nbsp;Jude Canon,&nbsp;Wenjun Ouyang","doi":"10.1002/ggn2.202200002","DOIUrl":"10.1002/ggn2.202200002","url":null,"abstract":"<p>Liver metastasis is associated with immunotherapy resistance, although the underlying mechanisms remain incompletely understood. By applying single cell RNA-sequencing to a concurrent subcutaneous and liver tumor murine model to recapitulate liver metastases, it is identified that subsets within tumor-infiltrating exhausted CD8⁺ T (Tex) cells and immunosuppressive tumor-associated macrophages (TAMs) display opposite responses to concurrent liver tumors and anti-PD-1 treatment, suggesting a complex immune regulating network. Both angiogenic and interferon-reactive TAMs show increased frequencies in implanted liver tumors, and anti-PD-1 treatment further elevates the frequencies of angiogenic TAMs. Such TAMs frequencies negatively correlate with the proportions of cytotoxic T cell subsets. Further, expression of interferon-stimulated genes in TAMs is dramatically reduced under effective anti-PD-1 treatment, while such tendencies are diminished in mice with implanted liver tumors. Therefore, the study indicates that liver metastases could increase immunosuppressive TAMs frequencies and inhibit Tex responses to PD-1 blockade, resulting in compromised systemic antitumor immunity and limited immunotherapy efficacy.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9993474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9157267","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":"An Improved Model for Circular RNA Overexpression: Using the Actin Intron Reveals High Circularization Efficiency","authors":"Feiya Li,&nbsp;Juanjuan Lyu,&nbsp;Yang Yang,&nbsp;Qiwei Yang,&nbsp;Cristian Santos,&nbsp;Burton B. Yang","doi":"10.1002/ggn2.202200019","DOIUrl":"10.1002/ggn2.202200019","url":null,"abstract":"<p>Traditionally, the group 1 intron of the T4 <i>td</i> gene is used to generate a foreign circular sequence. However, the T4 system has been shown to be fairly inefficient in expressing circular RNA (circRNA). Here, a new method is developed to express circular sequences with high circularization efficiency to strengthen the confidence for future circRNA functional studies. CircRNA expression plasmids, constructed with different lengths derived from the actin intron (15-nt, 30-nt, 60-nt, 100-nt, 180-nt) and T4 intron, are introduced into human and mouse cell lines 293T and B16. Junction detection and sequencing are used to determine successful circularization of introns and their expression efficiencies. An actin intron with a medium length (60-nt–100-nt) shows significantly increased efficiency of circularization, whereas intron-100-nt shows the best efficiency in most conditions. RNA pull-down assays are designed to precipitate the splicing factors that are bound to the introns and intron/exon junction. The precipitated proteins are analyzed by mass spectrometry (MS), aiming to identify the possible underlying mechanism behind the high circularization efficiency. This expression system has been validated using different circRNAs, and such method shows potential in contributing to the expanding field of circRNA studies.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.202200019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41175232","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":"Editorial Board: (Advanced Genetics 3/03)","authors":"","doi":"10.1002/ggn2.202270032","DOIUrl":"https://doi.org/10.1002/ggn2.202270032","url":null,"abstract":"","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.202270032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91830996","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":"Persistent Parental RNAi in the Beetle Tribolium castaneum Involves Maternal Transmission of Long Double-Stranded RNA (Advanced Genetics 3/03)","authors":"Thorsten Horn,&nbsp;Kalin D. Narov,&nbsp;Kristen A. Panfilio","doi":"10.1002/ggn2.202270031","DOIUrl":"https://doi.org/10.1002/ggn2.202270031","url":null,"abstract":"<p><b>dsRNA Uptake</b></p><p>In article 2100064 by Kristen A. Panfilio and co-workers, the cuticle exoskeleton of flour beetle larvae reveals normal anatomy (above: head-to-tail in blue-to-red) and long-term parental RNAi knockdown (below), here showing a mirror-image duplication of the abdomen (red termini to yellow center). Strong knockdown can persist for months despite transmission of full-length double-stranded RNA (dsRNA) from the mother into the egg, depleting maternal dsRNA levels.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.202270031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91559508","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":"Trauma Matters: Integrating Genetic and Environmental Components of PTSD","authors":"Shelby Marchese,&nbsp;Laura M. Huckins","doi":"10.1002/ggn2.202200017","DOIUrl":"10.1002/ggn2.202200017","url":null,"abstract":"<p>Trauma is ubiquitous, but only a subset of those who experience trauma will develop posttraumatic stress disorder (PTSD). In this review, it is argued that to determine who is at risk of developing PTSD, it is critical to examine the genetic etiology of the disorder and individual trauma profiles of those who are susceptible. First, the state of current PTSD genetic research is described, with a particular focus on studies that present evidence for trauma type specificity, or for differential genetic etiology according to gender or race. Next, approaches that leverage non-traditional phenotyping approaches are reviewed to identify PTSD-associated variants and biology, and the relative advantages and limitations inherent in these studies are reflected on. Finally, it is discussed how trauma might influence the heritability of PTSD, through type, risk factors, genetics, and associations with PTSD symptomology.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ggn2.202200017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41158692","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}