Advanced genetics (Hoboken, N.J.)最新文献

The study of mutations that impact fertility has a catch-22. Fertility mutants are often lost since they cannot simply be propagated and maintained. This has hindered progress in understanding the genetics of fertility. In mice, several molecules are found to be required for the interactions between the sperm and egg, with JUNO and IZUMO1 being the only known receptor pair on the egg and sperm surface, respectively. In Caenorhabditis elegans, a total of 12 proteins on the sperm or oocyte have been identified to mediate gamete interactions. Majority of these genes were identified through mutants isolated from genetic screens. In this review, we summarize the several key screening strategies that led to the identification of fertility mutants in C. elegans and provide a perspective about future research using genetic approaches. Recently, advancements in new technologies such as high-throughput sequencing and Crispr-based genome editing tools have accelerated the molecular, cell biological, and mechanistic analysis of fertility genes. We review how these valuable tools advance our understanding of the molecular underpinnings of fertilization. We draw parallels of the molecular mechanisms of fertilization between worms and mammals and argue that our work in C. elegans complements fertility research in humans and other species.

Male juvenile zebra finches learn to sing by imitating songs of adult males early in life. The development of the song control circuit and song learning and maturation are highly intertwined processes, involving gene expression, neurogenesis, circuit formation, synaptic modification, and sensory-motor learning. To better understand the genetic and genomic mechanisms underlying these events, we used RNA-Seq to examine genome-wide transcriptomes in the song control nucleus HVC of male juvenile (45 d) and adult (100 d) zebra finches. We report that gene groups related to axon guidance, RNA processing, lipid metabolism, and mitochondrial functions show enriched expression in juvenile HVC compared to the rest of the brain. As juveniles mature into adulthood, massive gene expression changes occur. Expression of genes related to amino acid metabolism, cell cycle, and mitochondrial function is reduced, accompanied by increased and enriched expression of genes with synaptic functions, including genes related to G-protein signaling, neurotransmitter receptors, transport of small molecules, and potassium channels. Unexpectedly, a group of genes with immune system functions is also developmentally regulated, suggesting potential roles in the development and functions of HVC. These data will serve as a rich resource for investigations into the development and function of a neural circuit that controls vocal behavior.

DNA methylation is a critical process in the regulation of gene expression with dramatic effects in development and continually expanding roles in oncogenesis. 5-Methylcytosine was once considered to be an inherited and stably repressive epigenetic mark, which can be only removed by passive dilution during multiple rounds of DNA replication. However, in the past two decades, physiologically controlled DNA demethylation and deamination processes have been identified, thereby revealing the function of cytosine methylation as a highly regulated and complex state—not simply a static, inherited signature or binary on-off switch. Alongside these fundamental discoveries, clinical studies over the past decade have revealed the dramatic consequences of aberrant DNA demethylation. In this review we discuss DNA demethylation and deamination in the context of 5-methylcytosine as critical processes for physiological and physiopathological transitions within three states—development, immune maturation, and oncogenic transformation; and we describe the expanding role of DNA demethylating drugs as therapeutic agents in cancer.

A mechanistic understanding of the natural aging process, which is distinct from aging-related disease mechanisms, is essential for developing interventions to extend lifespan or healthspan. Here, we discuss current trends in aging research and address conceptual and experimental challenges in the field. We examine various molecular markers implicated in aging with an emphasis on the role of heterochromatin and epigenetic changes. Studies in model organisms have been advantageous in elucidating conserved genetic and epigenetic mechanisms and assessing interventions that affect aging. We highlight the use of Drosophila, which allows controlled studies for evaluating genetic and environmental contributors to aging conveniently. Finally, we propose the use of novel methodologies and future strategies using Drosophila in aging research.

Strong selection has resulted in substantial morphological and behavioral diversity across modern dog breeds, which makes dogs interesting model animals to study the underlying genetic architecture of these traits. However, results from between-breed analyses may confound selection signatures for behavior and morphological features that were coselected during breed development. In this study, we assess population genetic differences in a unique resource of dogs of the same breed but with systematic behavioral selection in only one population. We exploit these different breeding backgrounds to identify signatures of recent selection. Selection signatures within populations were found on chromosomes 4 and 19, with the strongest signals in behavior-related genes. Regions showing strong signals of divergent selection were located on chromosomes 1, 24, and 32, and include candidate genes for both physical features and behavior. Some of the selection signatures appear to be driven by loci associated with coat color (Chr 24; ASIP) and length (Chr 32; FGF5), while others showed evidence of association with behavior. Our findings suggest that signatures of selection within dog breeds have been driven by selection for morphology and behavior. Furthermore, we demonstrate that combining selection scans with association analyses is effective for dissecting the traits under selection.

Advanced age is associated with accumulation of damage and other deleterious changes and a consequential systemic decline of function. This decline affects all organs and systems in an organism, leading to their inadaptability to the environment, and therefore is thought to be inevitable for humans and most animal species. However, in vitro and in vivo application of reprogramming strategies, which convert somatic cells to induced pluripotent stem cells, has demonstrated that the aged cells can be rejuvenated. Moreover, the data and theoretical considerations suggest that reversing the biological age of somatic cells (from old to young) and de-differentiating somatic cells into stem cells represent two distinct processes that take place during rejuvenation, and thus they may be differently targeted. We advance a stemness-function model to explain these data and discuss a possibility of rejuvenation from the perspective of damage accumulation. In turn, this suggests approaches to achieve rejuvenation of cells in vitro and in vivo.

Despite an explosive growth of next-generation sequencing data, genome diagnostics only provides a molecular diagnosis to a minority of patients. Software tools that prioritize genes based on patient symptoms using known gene-disease associations may complement variant filtering and interpretation to increase chances of success. However, many of these tools cannot be used in practice because they are embedded within variant prioritization algorithms, or exist as remote services that cannot be relied upon or are unacceptable because of legal/ethical barriers. In addition, many tools are not designed for command-line usage, closed-source, abandoned, or unavailable. We present Variant Interpretation using Biomedical literature Evidence (VIBE), a tool to prioritize disease genes based on Human Phenotype Ontology codes. VIBE is a locally installed executable that ensures operational availability and is built upon DisGeNET-RDF, a comprehensive knowledge platform containing gene-disease associations mostly from literature and variant-disease associations mostly from curated source databases. VIBE's command-line interface and output are designed for easy incorporation into bioinformatic pipelines that annotate and prioritize variants for further clinical interpretation. We evaluate VIBE in a benchmark based on 305 patient cases alongside seven other tools. Our results demonstrate that VIBE offers consistent performance with few cases missed, but we also find high complementarity among all tested tools. VIBE is a powerful, free, open source and locally installable solution for prioritizing genes based on patient symptoms. Project source code, documentation, benchmark and executables are available at https://github.com/molgenis/vibe.

Planet Earth has experienced many dramatic atmospheric and climatic changes throughout its 4.5-billion-year history that have profoundly impacted the evolution of life as we know it. Photosynthetic organisms, and specifically plants, have played a paramount role in shaping the Earth's atmosphere through oxygen production and carbon sequestration. In turn, the diversity of plants has been shaped by historical atmospheric and climatic changes: plants rose to this challenge by evolving new developmental and metabolic traits. These adaptive traits help plants to thrive in diverse growth conditions, while benefiting humanity through the production of food, raw materials, and medicines. However, the current rapid rate of climate change caused by human activities presents unprecedented new challenges to the future of plants. Here, we discuss the potential effects of modern climate change on plants, with specific attention to plant specialized metabolism. We explore potential avenues of future scientific investigations, powered by cutting-edge methods such as synthetic biology and genome engineering, to better understand and mitigate the consequences of rapid climate change on plant fitness and plant usage by humans.

Research in genetics provides the basis for understanding the function and evolution of all living things. The disciplines of reading and writing genomes translate into sustainable economic development with the rational global goals of food security, maternal and child health, precision medicine, education and access to informatics technologies. We believe that many publications in our field are motivated by these goals and contain reusable modular elements that can be recombined both in research and in its translation, to attain them. Open research entails sharing not only the conclusions of science, but its materials, provenance, and gestation for the widest reuse by human and computational users. This means that we and our readers deplore any hiding or obscuring data sets or methods, and regret data sets in formally public repositories that have very slow accession or transfer rates. However, we will endeavor to work with all data producers who make contributions in good faith to genetics and genomics research.

Advanced Genetics is an Open Research journal from Wiley, published online using the CC-BY 4.0 open attribution license to encourage maximum credit and rapid creative reuse of all scholarly work. We are delighted to receive Original Research Articles, Resources, Analysis, Technical Reports, and Perspectives in the areas of human, animal, plant and microbial genetics, genomics, and epigenomics, selecting those reports for peer review that we judge editorially to have the highest research utility, ethical standards, and societal impact. As professional, full-time editors at Wiley, we take responsibility for all manuscript decisions and peer reviewer assignment. Our Advisory Board Members have a complementary role to guide Advanced Genetics's mission as they see fit, anticipating the evolution of research and standards in our field, and, with us, providing leadership in promoting excellence in open research. Unlike Editorial Board members at some journals, Advanced Genetics advisors are our mentors, not manuscript editors. We welcome their commitment to the journal for as long as they wish, and advisors may leave or rejoin the board at will.

Since we offer an online journal, we are happy to consider reports in any format for peer review, provided they would not burden referees with their unusual length or complexity. We also welcome presubmission enquiries via our online database. Author and data set contributions and consortium roles can be described via the CRediT contributor taxonomy (https://www.casrai.org/credit.html). We support a range of community standards and databases and the FAIRSharing1 community standards site (https://fairsharing.org) for best practices and semantic precision. The journal endorses the FAIR2 data principles (https://www.go-fair.org/fair-principles/) and we recommend database submission of data sets and workflows to replace most of the prior use cas