Genetics最新文献

{"title":"Wolbachia pipientis modulates germline stem cells and gene expression associated with ubiquitination and histone lysine trimethylation to rescue fertility defects in Drosophila.","authors":"Catherine H Kagemann, Jaclyn E Bubnell, Gabriela M Colocho, Daniela C Arana, Charles F Aquadro","doi":"10.1093/genetics/iyae220","DOIUrl":"10.1093/genetics/iyae220","url":null,"abstract":"<p><p>Wolbachia pipientis are maternally transmitted endosymbiotic bacteria commonly found in arthropods and nematodes. These bacteria manipulate reproduction of the host to increase their transmission using mechanisms, such as cytoplasmic incompatibility, that favor infected female offspring. The underlying mechanisms of reproductive manipulation by W. pipientis remain unresolved. Interestingly, W. pipientis infection partially rescues female fertility in flies containing hypomorphic mutations of bag of marbles (bam) in Drosophila melanogaster, which plays a key role in germline stem cell daughter differentiation. Using RNA-seq, we find that W. pipientis infection in bam hypomorphic females results in differential expression of many of bam's genetic and physical interactors and enrichment of ubiquitination and histone lysine methylation genes. We find that W. pipientis also rescues the fertility and germline stem cell functions of a subset of these genes when knocked down with RNAi in a wild-type bam genotype. Our results show that W. pipientis interacts with ubiquitination and histone lysine methylation genes which could be integral to the mechanism by which W. pipientis modulates germline stem cell gene function.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trait genetic architecture and population structure determine model selection for genomic prediction in natural Arabidopsis thaliana populations.","authors":"Patrick M Gibbs, Jefferson F Paril, Alexandre Fournier-Level","doi":"10.1093/genetics/iyaf003","DOIUrl":"10.1093/genetics/iyaf003","url":null,"abstract":"<p><p>Genomic prediction applies to any agro- or ecologically relevant traits, with distinct ontologies and genetic architectures. Selecting the most appropriate model for the distribution of genetic effects and their associated allele frequencies in the training population is crucial. Linear regression models are often preferred for genomic prediction. However, linear models may not suit all genetic architectures and training populations. Machine learning approaches have been proposed to improve genomic prediction owing to their capacity to capture complex biology including epistasis. However, the applicability of different genomic prediction models, including non-linear, non-parametric approaches, has not been rigorously assessed across a wide variety of plant traits in natural outbreeding populations. This study evaluates genomic prediction sensitivity to trait ontology and the impact of population structure on model selection and prediction accuracy. Examining 36 quantitative traits in 1,000+ natural genotypes of the model plant Arabidopsis thaliana, we assessed the performance of penalized regression, random forest, and multilayer perceptron at producing genomic predictions. Regression models were generally the most accurate, except for biochemical traits where random forest performed best. We link this result to the genetic architecture of each trait-notably that biochemical traits have simpler genetic architecture than macroscopic traits. Moreover, complex macroscopic traits, particularly those related to flowering time and yield, were strongly correlated to population structure, while molecular traits were better predicted by fewer, independent markers. This study highlights the relevance of machine learning approaches for simple molecular traits and underscores the need to consider ancestral population history when designing training samples.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel genome-wide association study method for detecting quantitative trait loci interacting with complex population structures in plant genetics.","authors":"Kosuke Hamazaki, Hiroyoshi Iwata, Tristan Mary-Huard","doi":"10.1093/genetics/iyaf038","DOIUrl":"https://doi.org/10.1093/genetics/iyaf038","url":null,"abstract":"<p><p>In plant genetics, most modern association analyses are performed on panels that bring together individuals from several populations, including admixed individuals whose genomes comprise chromosomal regions from different populations. These panels can identify quantitative trait loci (QTLs) with population-specific effects and epistatic interactions between QTLs and polygenic backgrounds. However, analyzing a diverse panel constitutes a challenge for statistical analysis. The statistical model must account for possible interactions between a QTL and the panel structure while strictly controlling the detection error rate. Although models to detect population-specific QTLs have already been developed, they rely on prior information about the population structure. In practice, this prior information may be missing as many genome-wide association study (GWAS) panels exhibit complex population structures. The present study introduces 2 new models for detecting QTLs interacting with complex population structures. Both incorporate an interaction term between single nucleotide polymorphism/haplotype block and genetic background into conventional GWAS models. The proposed models were compared with state-of-the-art models through simulation studies that considered QTLs with different levels of interaction with their genetic backgrounds. Results showed that models matching simulation settings were most effective for detecting corresponding QTLs while the proposed models outperformed classical models in detecting QTLs interacting with polygenes. Additionally, when applied to a soybean dataset, one of our models identified putative associated QTLs that conventional models failed to detect. The new models, implemented in the RAINBOWR package available on CRAN, are expected to help uncover complex trait genetic architectures.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Saccharomyces Genome Database: advances in genome annotation, expanded biochemical pathways, and other key enhancements.","authors":"Stacia R Engel, Suzi Aleksander, Robert S Nash, Edith D Wong, Shuai Weng, Stuart R Miyasato, Gavin Sherlock, J Michael Cherry","doi":"10.1093/genetics/iyae185","DOIUrl":"10.1093/genetics/iyae185","url":null,"abstract":"<p><p>Budding yeast (Saccharomyces cerevisiae) is the most extensively characterized eukaryotic model organism and has long been used to gain insight into the fundamentals of genetics, cellular biology, and the functions of specific genes and proteins. The Saccharomyces Genome Database (SGD) is a scientific resource that provides information about the genome and biology of S. cerevisiae. For more than 30 years, SGD has maintained the genetic nomenclature, chromosome maps, and functional annotation for budding yeast along with search and analysis tools to explore these data. Here, we describe recent updates at SGD, including the 2 most recent reference genome annotation updates, expanded biochemical pathway representation, changes to SGD search and data files, and other enhancements to the SGD website and user interface. These activities are part of our continuing effort to promote insights gained from yeast to enable the discovery of functional relationships between sequence and gene products in fungi and higher eukaryotes.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Drosophila model of mucopolysaccharidosis IIIB.","authors":"Bibhu Simkhada, Nestor O Nazario-Yepiz, Patrick S Freymuth, Rachel A Lyman, Vijay Shankar, Kali Wiggins, Heather Flanagan-Steet, Amrita Basu, Ryan J Weiss, Robert R H Anholt, Trudy F C Mackay","doi":"10.1093/genetics/iyae219","DOIUrl":"10.1093/genetics/iyae219","url":null,"abstract":"<p><p>Mucopolysaccharidosis type IIIB is a rare lysosomal storage disorder caused by defects in alpha-N-acetylglucosaminidase (NAGLU) and characterized by severe effects in the central nervous system. Mutations in NAGLU cause accumulation of partially degraded heparan sulfate in lysosomes. The consequences of these mutations on whole-genome gene expression and their causal relationships to neural degeneration remain unknown. Here, we used the functional Drosophila melanogaster ortholog of NAGLU, Naglu, to develop a fly model for MPS IIIB induced by gene deletion (NagluKO), missense (NagluY160C), and nonsense (NagluW422X) mutations. We used the Drosophila activity monitoring system to analyze activity and sleep and found sex- and age-dependent hyperactivity and sleep defects in mutant flies. Fluorescence microscopy on mutant fly brains using Lysotracker dye revealed a significant increase in acidic compartments. Differentially expressed genes determined from RNA sequencing of fly brains are involved in biological processes that affect nervous system development. A genetic interaction network constructed using known interacting partners of these genes consists of 2 major subnetworks, one of which is enriched in genes associated with synaptic function and the other with neurodevelopmental processes. Our data indicate that lysosomal dysfunction arising from disruption of heparan sulfate breakdown has widespread effects on the steady state of intracellular vesicle transport, including vesicles associated with synaptic transmission. Evolutionary conservation of fundamental biological processes predicts that the Drosophila model of mucopolysaccharidosis type IIIB can serve as an in vivo system for the future development of therapies for mucopolysaccharidosis type IIIB and related disorders.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZFIN updates to support zebrafish environmental exposure data.","authors":"Yvonne M Bradford, Ceri E Van Slyke, Jonathan B Muyskens, Wei-Chia Tseng, Douglas G Howe, David Fashena, Ryan Martin, Holly Paddock, Christian Pich, Sridhar Ramachandran, Leyla Ruzicka, Amy Singer, Ryan Taylor, Monte Westerfield","doi":"10.1093/genetics/iyaf021","DOIUrl":"10.1093/genetics/iyaf021","url":null,"abstract":"<p><p>The Zebrafish Information Network (ZFIN, zfin.org) is the database resource for genetic, genomic, and phenotypic data from research using zebrafish, Danio rerio. ZFIN curates information about genetic perturbations, gene expression, phenotype, gene function, and human disease models from zebrafish research publications and makes these data available to researchers worldwide. Over the past 20 years, zebrafish have increasingly been used to investigate the effects of environmental exposures, becoming an ideal model to study toxicity, phenotypic outcomes, and gene-chemical interactions. Despite this, database resources supporting zebrafish toxicology and environmental exposure research are limited. To fill this gap, ZFIN has expanded functionality to incorporate and convey toxicology data better. ZFIN annotations for gene expression, phenotype, and human disease models include information about genotypes and experimental conditions used. One type of experimental condition the database captures is the application of chemicals to zebrafish. ZFIN annotates chemicals using the Chemical Entities of Biological Interest Ontology (ChEBI) along with the Zebrafish Experimental Conditions Ontology (ZECO) to denote route of exposure and other experimental conditions. These features allow researchers to search phenotypes and human disease models linked to chemicals more efficiently. Here, we discuss how experimental conditions are displayed on ZFIN web pages, the data displayed on chemical term pages, and how to search and download data associated with chemical exposure experiments.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimating effective population size trajectories from time-series identity-by-descent segments.","authors":"Yilei Huang, Shai Carmi, Harald Ringbauer","doi":"10.1093/genetics/iyae212","DOIUrl":"10.1093/genetics/iyae212","url":null,"abstract":"<p><p>Long, identical haplotypes shared between pairs of individuals, known as identity-by-descent (IBD) segments, result from recently shared co-ancestry. Various methods have been developed to utilize IBD sharing for demographic inference in contemporary DNA data. Recent methodological advances have extended the screening for IBD segments to ancient DNA (aDNA) data, making demographic inference based on IBD also possible for aDNA. However, aDNA data typically have varying sampling times, but most demographic inference methods for modern data assume that sampling is contemporaneous. Here, we present Ttne (Time-Transect Ne), which models time-transect sampling to infer recent effective population size trajectories. Using simulations, we show that utilizing IBD sharing in time series increased resolution to infer recent fluctuations in effective population sizes compared with methods that only use contemporaneous samples. To account for IBD detection errors common in empirical analyses, we implemented an approach to estimate and model IBD detection errors. Finally, we applied Ttne to two aDNA time transects: individuals associated with the Copper Age Corded Ware Culture and Medieval England. In both cases, we found evidence of a growing population, a signal consistent with archaeological records.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-recombining genomic regions affect demography inference based on ancestral recombination graphs.","authors":"Jun Ishigohoka, Miriam Liedvogel","doi":"10.1093/genetics/iyaf004","DOIUrl":"10.1093/genetics/iyaf004","url":null,"abstract":"<p><p>Multiple methods of demography inference are based on the ancestral recombination graph. This powerful approach uses observed mutations to model local genealogies changing along chromosomes by historical recombination events. However, inference of underlying genealogies is difficult in regions with high recombination rate relative to mutation rate due to the lack of mutations representing genealogies. Despite the prevalence of high-recombining genomic regions in some organisms, such as birds, its impact on demography inference based on ancestral recombination graphs has not been well studied. Here, we use population genomic simulations to investigate the impact of high-recombining regions on demography inference based on ancestral recombination graphs. We demonstrate that inference of effective population size and the time of population split events is systematically affected when high-recombining regions cover wide breadths of the chromosomes. Excluding high-recombining genomic regions can practically mitigate this impact, and population genomic inference of recombination maps is informative in defining such regions although the estimated values of local recombination rate can be biased. Finally, we confirm the relevance of our findings in empirical analysis by contrasting demography inferences applied for a bird species, the Eurasian blackcap (Sylvia atricapilla), using different parts of the genome with high and low recombination rates. Our results suggest that demography inference methods based on ancestral recombination graphs should be carried out with caution when applied in species whose genomes contain long stretches of high-recombining regions.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic changes in neuronal and glial GAL4 driver expression during Drosophila aging.","authors":"Caroline Delandre, John P D McMullen, Owen J Marshall","doi":"10.1093/genetics/iyaf014","DOIUrl":"10.1093/genetics/iyaf014","url":null,"abstract":"<p><p>Understanding how diverse cell types come together to form a functioning brain relies on the ability to specifically target these cells. This is often done using genetic tools such as the GAL4/UAS system in Drosophila melanogaster. Surprisingly, despite its extensive usage during studies of the aging brain, detailed spatiotemporal characterization of GAL4 driver lines in adult flies has been lacking. Here, we show that 3 commonly used neuronal drivers (elav[C155]-GAL4, nSyb[R57C10]-GAL4, and ChAT-GAL4) and the commonly used glial driver repo-GAL4 all show rapid and pronounced decreases in activity over the first 1.5 weeks of adult life, with activity becoming undetectable in some regions after 30 days (at 18°C). In addition to an overall decrease in GAL4 activity over time, we found notable differences in spatial patterns, mostly occurring soon after eclosion. Although all lines showed these changes, the nSyb-GAL4 line exhibited the most consistent and stable expression patterns over aging. Our findings suggest that gene transcription of key loci decreases in the aged brain, a finding broadly similar to previous work in mammalian brains. Our results also raise questions over past work on long-term expression of disease models in the brain and stress the need to find better genetic tools for ageing studies.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Unified Phenotype Ontology : a framework for cross-species integrative phenomics.","authors":"Nicolas Matentzoglu, Susan M Bello, Ray Stefancsik, Sarah M Alghamdi, Anna V Anagnostopoulos, James P Balhoff, Meghan A Balk, Yvonne M Bradford, Yasemin Bridges, Tiffany J Callahan, Harry Caufield, Alayne Cuzick, Leigh C Carmody, Anita R Caron, Vinicius de Souza, Stacia R Engel, Petra Fey, Malcolm Fisher, Sarah Gehrke, Christian Grove, Peter Hansen, Nomi L Harris, Midori A Harris, Laura Harris, Arwa Ibrahim, Julius O B Jacobsen, Sebastian Köhler, Julie A McMurry, Violeta Munoz-Fuentes, Monica C Munoz-Torres, Helen Parkinson, Zoë M Pendlington, Clare Pilgrim, Sofia M C Robb, Peter N Robinson, James Seager, Erik Segerdell, Damian Smedley, Elliot Sollis, Sabrina Toro, Nicole Vasilevsky, Valerie Wood, Melissa A Haendel, Christopher J Mungall, James A McLaughlin, David Osumi-Sutherland","doi":"10.1093/genetics/iyaf027","DOIUrl":"10.1093/genetics/iyaf027","url":null,"abstract":"<p><p>Phenotypic data are critical for understanding biological mechanisms and consequences of genomic variation, and are pivotal for clinical use cases such as disease diagnostics and treatment development. For over a century, vast quantities of phenotype data have been collected in many different contexts covering a variety of organisms. The emerging field of phenomics focuses on integrating and interpreting these data to inform biological hypotheses. A major impediment in phenomics is the wide range of distinct and disconnected approaches to recording the observable characteristics of an organism. Phenotype data are collected and curated using free text, single terms or combinations of terms, using multiple vocabularies, terminologies, or ontologies. Integrating these heterogeneous and often siloed data enables the application of biological knowledge both within and across species. Existing integration efforts are typically limited to mappings between pairs of terminologies; a generic knowledge representation that captures the full range of cross-species phenomics data is much needed. We have developed the Unified Phenotype Ontology (uPheno) framework, a community effort to provide an integration layer over domain-specific phenotype ontologies, as a single, unified, logical representation. uPheno comprises (1) a system for consistent computational definition of phenotype terms using ontology design patterns, maintained as a community library; (2) a hierarchical vocabulary of species-neutral phenotype terms under which their species-specific counterparts are grouped; and (3) mapping tables between species-specific ontologies. This harmonized representation supports use cases such as cross-species integration of genotype-phenotype associations from different organisms and cross-species informed variant prioritization.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}