Advanced genetics (Hoboken, N.J.)最新文献

{"title":"Optogenetic-mediated cardiovascular differentiation and patterning of human pluripotent stem cells","authors":"Peter B. Hellwarth,&nbsp;Yun Chang,&nbsp;Arundhati Das,&nbsp;Po-Yu Liang,&nbsp;Xiaojun Lian,&nbsp;Nicole A. Repina,&nbsp;Xiaoping Bao","doi":"10.1002/ggn2.202100011","DOIUrl":"10.1002/ggn2.202100011","url":null,"abstract":"<p>Precise spatial and temporal regulation of dynamic morphogen signals during human development governs the processes of cell proliferation, migration, and differentiation to form organized tissues and organs. Tissue patterns spontaneously emerge in various human pluripotent stem cell (hPSC) models. However, the lack of molecular methods for precise control over signal dynamics limits the reproducible production of tissue patterns and a mechanistic understanding of self-organization. We recently implemented an optogenetic-based OptoWnt platform for light-controllable regulation of Wnt/β-catenin signaling in hPSCs for <i>in vitro</i> studies. Using engineered illumination devices to generate light patterns and thus precise spatiotemporal control over Wnt activation, here we triggered spatially organized transcriptional changes and mesoderm differentiation of hPSCs. In this way, the OptoWnt system enabled robust endothelial cell differentiation and cardiac tissue patterning <i>in vitro</i>. Our results demonstrate that spatiotemporal regulation of signaling pathways via synthetic OptoWnt enables instructive stem cell fate engineering and tissue patterning.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ggn2.202100011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10509210","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":"A phylogenetic analysis of the wild Tulipa species (Liliaceae) of Kosovo based on plastid and nuclear DNA sequence","authors":"Avni Hajdari,&nbsp;Bledar Pulaj,&nbsp;Corinna Schmiderer,&nbsp;Xhavit Mala,&nbsp;Brett Wilson,&nbsp;Kimete Lluga-Rizani,&nbsp;Behxhet Mustafa","doi":"10.1002/ggn2.202100016","DOIUrl":"10.1002/ggn2.202100016","url":null,"abstract":"<p>In Kosovo, the genus <i>Tulipa</i> is represented by eight taxa, most of which form a species complex surrounding <i>Tulipa scardica</i>. To investigate the phylogenetic relationship of these <i>Tulipa</i> species a Bayesian analysis was undertaken using the ITS nuclear marker and <i>trnL-trnF</i>, <i>rbcL</i> and <i>psbA-trnH</i> plastid markers. The resulting phylogenetic trees show that Kosovarian <i>Tulipa</i> species consistently group into two main clades, the subgenera <i>Eriostemones</i> and <i>Tulipa</i>. Furthermore, our analyses provide some evidence that the subspecies of <i>Tulipa sylvestris</i> are genetically distinguishable, however not significantly enough to support their reclassification as species. In contrast, the markers provide some novel information to reassess the species concepts of the <i>T</i>. <i>scardica</i> complex. Our data provide support for the synonymisation of <i>Tulipa luanica</i> and <i>Tulipa kosovarica</i> under the species <i>Tulipa serbica</i>. Resolution and sampling limitations hinder any concrete conclusion about whether <i>Tulipa albanica</i> and <i>T</i>. <i>scardica</i> are true species, yet our data do provide some support that these are unique taxa and therefore should continue to be treated as such until further clarification. Overall, our work shows that genetic data will be important in determining species concepts in this genus, however, even with a molecular perspective pulling apart closely related taxa can be extremely challenging.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ggn2.202100016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10509209","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":"The genomic origin of Zana of Abkhazia","authors":"Ashot Margaryan,&nbsp;Mikkel-Holger S. Sinding,&nbsp;Christian Carøe,&nbsp;Vladimir Yamshchikov,&nbsp;Igor Burtsev,&nbsp;M. Thomas P. Gilbert","doi":"10.1002/ggn2.10051","DOIUrl":"10.1002/ggn2.10051","url":null,"abstract":"<p>Enigmatic phenomena have sparked the imagination of people around the globe into creating folkloric creatures. One prime example is Zana of Abkhazia (South Caucasus), a well-documented 19th century female who was captured living wild in the forest. Zana's appearance was sufficiently unusual, that she was referred to by locals as an Almasty—the analog of Bigfoot in the Caucasus. Although the exact location of Zana's burial site was unknown, the grave of her son, Khwit, was identified in 1971. The genomes of Khwit and the alleged Zana skeleton were sequenced to an average depth of ca. 3× using ancient DNA techniques. The identical mtDNA and parent-offspring relationship between the two indicated that the unknown woman was indeed Zana. Population genomic analyses demonstrated that Zana's immediate genetic ancestry can likely be traced to present-day East-African populations. We speculate that Zana might have had a genetic disorder such as congenital generalized hypertrichosis which could partially explain her strange behavior, lack of speech, and long body hair. Our findings elucidate Zana's unfortunate story and provide a clear example of how prejudices of the time led to notions of cryptic hominids that are still held and transmitted by some today.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ggn2.10051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10857452","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":"Design of a FAIR digital data health infrastructure in Africa for COVID-19 reporting and research","authors":"Mirjam van Reisen,&nbsp;Francisca Oladipo,&nbsp;Mia Stokmans,&nbsp;Mouhamed Mpezamihgo,&nbsp;Sakinat Folorunso,&nbsp;Erik Schultes,&nbsp;Mariam Basajja,&nbsp;Aliya Aktau,&nbsp;Samson Yohannes Amare,&nbsp;Getu Tadele Taye,&nbsp;Putu Hadi Purnama Jati,&nbsp;Kudakwashe Chindoza,&nbsp;Morgane Wirtz,&nbsp;Meriem Ghardallou,&nbsp;Gertjan van Stam,&nbsp;Wondimu Ayele,&nbsp;Reginald Nalugala,&nbsp;Ibrahim Abdullahi,&nbsp;Obinna Osigwe,&nbsp;John Graybeal,&nbsp;Araya Abrha Medhanyie,&nbsp;Abdullahi Abubakar Kawu,&nbsp;Fenghong Liu,&nbsp;Katy Wolstencroft,&nbsp;Erik Flikkenschild,&nbsp;Yi Lin,&nbsp;Joëlle Stocker,&nbsp;Mark A. Musen","doi":"10.1002/ggn2.10050","DOIUrl":"10.1002/ggn2.10050","url":null,"abstract":"<p>The limited volume of COVID-19 data from Africa raises concerns for global genome research, which requires a diversity of genotypes for accurate disease prediction, including on the provenance of the new SARS-CoV-2 mutations. The Virus Outbreak Data Network (VODAN)-Africa studied the possibility of increasing the production of clinical data, finding concerns about data ownership, and the limited use of health data for quality treatment at point of care. To address this, VODAN Africa developed an architecture to record clinical health data and research data collected on the incidence of COVID-19, producing these as human- and machine-readable data objects in a distributed architecture of locally governed, linked, human- and machine-readable data. This architecture supports analytics at the point of care and—through data visiting, across facilities—for generic analytics. An algorithm was run across FAIR Data Points to visit the distributed data and produce aggregate findings. The FAIR data architecture is deployed in Uganda, Ethiopia, Liberia, Nigeria, Kenya, Somalia, Tanzania, Zimbabwe, and Tunisia.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ggn2.10050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39412993","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":"FMR1 gene CGG repeat distribution among the three individual cohorts with intellectual disability, autism, and primary ovarian insufficiency from Tamil Nadu, Southern India","authors":"Indhumathi Nagarathinam,&nbsp;Samuel S. Chong,&nbsp;Thelma B. K.,&nbsp;Jeffrey Justin Margret,&nbsp;Viswanathan Venkataraman,&nbsp;Karthikeyen Natarajan Padmavathy,&nbsp;C. R. Srikumari Srisailapathy","doi":"10.1002/ggn2.10048","DOIUrl":"10.1002/ggn2.10048","url":null,"abstract":"<p>Fragile X syndrome is the most common genetic cause of intellectual disability (ID) and is also well known to have a role in primary ovarian insufficiency (POI) and fragile X-associated tremor ataxia syndrome (FXTAS) that expresses across generations. The objective was to compare the CGG repeat variants in <i>FMR1</i> gene among three correlating cohorts of ID, autism and idiopathic POI. Thirty-six patients with ID, 12 with autism spectrum disorder (ASD) and 13 females with idiopathic POI were screened for <i>FMR1</i> CGG repeat size by fluorescent methylation-specific PCR and GeneScan analysis, irrespective of Hagerman checklist clinical scores. Among 29 males and seven females, 11 <i>FMR1</i> allelic variants ranging from 21 to &gt;200 CGG repeats were observed. Three (CF2-3, 39-5, 44-2) out of 29 males had full mutation alleles accounting for a 10.34% incidence of FXS among idiopathic ID males. One of them was a mosaic for CGG repeats with both premutation and full mutation alleles. The frequency of fragile X syndrome is high among patients with idiopathic ID; they also had a high score for the clinical check list. A cascade testing that begins with checklist evaluation prior to DNA analysis will be cost-effective for establishing early diagnosis in South India. With the huge disease burden, there is a need for the establishment of more molecular diagnostics and self-help groups for fragile X syndrome.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ggn2.10048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10856997","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":"A network database for the human biobank","authors":"Myles Axton","doi":"10.1002/ggn2.10049","DOIUrl":"10.1002/ggn2.10049","url":null,"abstract":"<p>“Enduring trust is essential for lifelong collection of phenotypes and traits. Good metadata, local ownership and fair reuse of genomic and outcome data can be sustained in partnership among well-resourced and well-peopled regions of the world.“</p><p>A Perspective in this issue recounts the endeavors of the collaborative Virus Outbreak Data Access Network (VODAN)—Africa<span>²</span> that collected SARS-CoV-2 outcomes using electronic case report forms (eCRFs) and other templates and organized the data with FAIR metadata models in linked data for clinical decision making and research queries. One use case employed temporal, numerical and geolocator metadata to connect de-identified interviews with displaced people in Tunisia about their COVID-19 infection outcomes to media reports that aggregate information on the same groups. The metadata model and the data it describes were stored as linked data that could be remotely queried across the network of nine African countries.</p><p>Genome data is cheap, plentiful, and concentrated in a few wealthy places, even relative to the information web, where less than 1% of the world's servers serve over 99% of the web content.<span>¹</span> This situation arises because it is difficult to move petabytes of data (since it is hard drives rather than bytes that travel). Second, the need for efficient search over similar formats of data usually leads to centralized accumulation of resources. Third, trusted and secure sharing of data resources among distributed sites requires metadata standards and linked data conventions that permit both computer operations without parsing or data transformation and queries from human users who range from clinicians to bioinformaticians to government agencies. Finally, application of any agreed metadata standards needs to be rapid and very low cost if it is to be more than a specialized research and training exercise.</p><p>In contrast to genome data, personal experiences including exposures and clinical records are distributed across institutions, homes, families, and individuals. Lifelong trust that sharing this information brings better outcomes for the donors is essential if we are to use this living biobank of diverse experience to make sense of variation in both viral and human genomes. Information from affected and unaffected individuals is needed to understand the importance of even point mutations in small viral genomes—such as the SARS-CoV-2 variants that continue to cause so much disruption and disease worldwide. Yet this data has not been gathered from places where the disruption is occurring, largely because we do not yet have collection networks with the trust and capacity to sustainably return results within the region of study.</p><p>There are now several related functional technologies for linked data to deliver the aspirational goals laid out in the principles of FAIR data and services. These working together would amount to a mercanti","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ggn2.10049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10856996","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":"Evaluation of recurrent GNPTAB, GNPTG, and NAGPA variants associated with stuttering","authors":"Nandhini Devi Gunasekaran,&nbsp;Chandru Jayasankaran,&nbsp;Jeffrey Justin Margret,&nbsp;Mathuravalli Krishnamoorthy,&nbsp;C. R. Srikumari Srisailapathy","doi":"10.1002/ggn2.10043","DOIUrl":"10.1002/ggn2.10043","url":null,"abstract":"<p>Stuttering is a childhood-onset fluency disorder, intertwined with physiological, emotional, and anxiety factors. The present study was designed to evaluate the recurrence of the reported mutations among three previously implicated (<i>GNPTAB</i>, <i>GNPTG</i>, <i>NAGPA</i>) candidate genes, in persons with stuttering from south India. Mutation screening was performed among 64 probands on 12 specific exons, by Sanger sequencing. A total of 12 variants were identified, which included five nonsynonymous, five synonymous, and two noncoding variants. Three unrelated probands harbored heterozygous missense variants at conserved coding positions across species (p. Glu1200Lys in <i>GNPTAB</i>, p. Ile268Leu in <i>GNPTG</i> and p. Arg44Pro in <i>NAGPA</i>). Of these, only one variant (p. Glu1200Lys in <i>GNPTAB</i>) cosegregated with the affected status while p. Ile268Leu in <i>GNPTG</i> gene was found to be a rare de novo variant. Although this study identified some previously reported variants that have been claimed to have a role in stuttering, we confirmed only one of these to be a likely causal de novo variant (p.Ile268Leu) in the <i>GNPTG</i> gene at an allele frequency of 0.8% (1/128) in the families with stuttering.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ggn2.10043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10856993","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":"Genetic, epigenetic, and post-transcriptional basis of divergent tissue regenerative capacities among vertebrates","authors":"Sheamin Khyeam,&nbsp;Sukjun Lee,&nbsp;Guo N. Huang","doi":"10.1002/ggn2.10042","DOIUrl":"10.1002/ggn2.10042","url":null,"abstract":"<p>Regeneration is widespread across the animal kingdom but varies vastly across phylogeny and even ontogeny. Adult mammalian regeneration in most organs and appendages is limited, while vertebrates such as zebrafish and salamanders are able to regenerate various organs and body parts. Here, we focus on the regeneration of appendages, spinal cord, and heart—organs and body parts that are highly regenerative among fish and amphibian species but limited in adult mammals. We then describe potential genetic, epigenetic, and post-transcriptional similarities among these different forms of regeneration across vertebrates and discuss several theories for diminished regenerative capacity throughout evolution.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ggn2.10042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39338086","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":"A CRISPR/Cas9-based method for targeted DNA methylation enables cancer initiation in B lymphocytes","authors":"Shota Katayama,&nbsp;Koichi Shiraishi,&nbsp;Naoki Gorai,&nbsp;Masao Andou","doi":"10.1002/ggn2.10040","DOIUrl":"10.1002/ggn2.10040","url":null,"abstract":"<p>Targeted DNA methylation is important for understanding transcriptional modulation and epigenetic diseases. Although CRISPR-Cas9 has potential for this purpose, it has not yet been successfully used to efficiently introduce DNA methylation and induce epigenetic diseases. We herein developed a new system that enables the replacement of an unmethylated promoter with a methylated promoter through microhomology-mediated end joining-based knock-in. We successfully introduced an approximately 100% DNA methylation ratio at the cancer-associated gene SP3 in HEK293 cells. Moreover, engineered <i>SP3</i> promoter hypermethylation led to transcriptional suppression in human B lymphocytes and induced B-cell lymphoma. Our system provides a promising framework for targeted DNA methylation and cancer initiation through epimutations.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ggn2.10040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10512800","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":"Future trends in synthetic biology in Asia","authors":"Ning Mao,&nbsp;Nikhil Aggarwal,&nbsp;Chueh Loo Poh,&nbsp;Byung Kwan Cho,&nbsp;Akihiko Kondo,&nbsp;Chenli Liu,&nbsp;Wen Shan Yew,&nbsp;Matthew Wook Chang","doi":"10.1002/ggn2.10038","DOIUrl":"10.1002/ggn2.10038","url":null,"abstract":"<p>Synthetic biology research and technology translation has garnered increasing interest from the governments and private investors in Asia, where the technology has great potential in driving a sustainable bio-based economy. This Perspective reviews the latest developments in the key enabling technologies of synthetic biology and its application in bio-manufacturing, medicine, food and agriculture in Asia. Asia-centric strengths in synthetic biology to grow the bio-based economy, such as advances in genome editing and the presence of biofoundries combined with the availability of natural resources and vast markets, are also highlighted. The potential barriers to the sustainable development of the field, including inadequate infrastructure and policies, with suggestions to overcome these by building public-private partnerships, more effective multi-lateral collaborations and well-developed governance framework, are presented. Finally, the roles of technology, education and regulation in mitigating potential biosecurity risks are examined. Through these discussions, stakeholders from different groups, including academia, industry and government, are expectantly better positioned to contribute towards the establishment of innovation and bio-economy hubs in Asia.</p>","PeriodicalId":72071,"journal":{"name":"Advanced genetics (Hoboken, N.J.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/ggn2.10038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10512807","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}