Genetics最新文献

{"title":"Harnessing cytonuclear diversity to map barley spike traits using the cytonuclear multi-parent population.","authors":"Schewach Bodenheimer, Eyal Bdolach, Avital Be'ery, Lalit Dev Tiwari, Ruth Sarahi Perez-Alfaro, Shengming Yang, Daniel Koenig, Eyal Fridman","doi":"10.1093/genetics/iyaf167","DOIUrl":"10.1093/genetics/iyaf167","url":null,"abstract":"<p><p>The interplay between nuclear and cytoplasmic genomes, collectively known as cytonuclear interactions (CNIs), is increasingly recognized as a key driver of phenotypic variation and adaptive potential across diverse organisms. Yet, leveraging cytoplasmic diversity and fully understanding the role of CNIs in agriculturally important traits remain major challenges in crop improvement. Here, we present the Cytonuclear Multi-Parent Population (CMPP), a novel interspecific resource comprising 951 doubled haploid lines, generated from 2 backcrosses between ten genetically diverse wild barley accessions (Hordeum vulgare ssp. spontaneum) used as female founders and the elite cultivar Noga (H. vulgare). Phenotyping across multiple environments revealed that up to 5% of variation in key spike and grain trait values are explained by cytoplasm (η2 = 0.05). Notably, wild cytoplasms influenced trait stability, with the B1K-50-04 cytoplasm increasing grain weight stability based on Shukla's measure. Genome-wide association studies employing Nested Association Mapping (NAM), FASTmrMLM, and MatrixEpistasis (ME) identified 76 marker-trait associations (MTAs). The ME approach specifically uncovered 16 cytonuclear QTL (cnQTL) exhibiting cytoplasm-dependent effects. Furthermore, we developed a genomic prediction strategy incorporating interactions between significant MTAs and population structure variables (subfamily and cytoplasm), which achieved cross-validation accuracies comparable to, or even exceeding, models using the full set of 6,679 SNPs, despite utilizing substantially fewer predictors, enabling quicker and more efficient validation runs. The CMPP provides a unique platform for dissecting cytoplasmic effects and CNIs, highlighting the importance of incorporating cytonuclear context in genetic mapping and prediction to effectively harness both nuclear and cytoplasmic diversity for crop improvement.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884144","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":"Histone acetylation by SAGA complex but not by NuA4 complex is required for filamentation program in Candida albicans.","authors":"Priyanka Nagar, Basharat Bashir Teli, Divya Dinesh, Krishnamurthy Natarajan","doi":"10.1093/genetics/iyaf159","DOIUrl":"10.1093/genetics/iyaf159","url":null,"abstract":"<p><p>Candida albicans, a major human fungal pathogen undergoes filamentation from yeast to hyphal state under filamentation-inducing conditions. Gcn5 and Esa1 are key histone H3 and H4 acetyltransferases, respectively, encoded by the budding yeast and other eukaryotes. While Gcn5, a subunit of the SAGA complex, and Esa1, a subunit of the NuA4 complex, are critical for C. albicans virulence and hyphal induction, how the relative HAT activities impinge on hyphal gene expression during filamentation is less understood. We found that hyphal gene promoters are hyperacetylated at H3K9 and H4 upon filamentation. By creating point mutations in the HAT domain of Gcn5 and Esa1, we investigated the relative requirement of the SAGA and NuA4 HAT activities for filamentation response. We show that Gcn5 HAT activity is essential for hyperacetylation of H3K9 and H4 at promoters and across hyphal gene ORFs. Surprisingly, the Esa1 HAT domain mutation did not impair H4 acetylation at hyphal genes suggesting that Gcn5 HAT activity is sufficient for H4 (and H3K9) acetylation. Paradoxically, the Esa1 HAT mutant formed filaments constitutively and showed elevated H3K9ac and H4ac at promoters under inducing conditions. Furthermore, we show that the basic helix-loop-helix transcriptional regulator Efg1 is essential for Gcn5-mediated hyperacetylation and RNA pol II recruitment to promoters. Thus, our results indicate that the SAGA-mediated H3K9 and H4 acetylation is sufficient and essential for induction of C. albicans filamentation.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838351","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":"Environmental NaCl affects Caenorhabditis elegans development and aging.","authors":"Franziska Pohl, Brian M Egan, Daniel L Schneider, Matthew C Mosley, Micklaus A Garcia, Sydney Hou, Chen-Hao Chiu, Kerry Kornfeld","doi":"10.1093/genetics/iyaf139","DOIUrl":"10.1093/genetics/iyaf139","url":null,"abstract":"<p><p>Sodium chloride (NaCl) is an essential nutrient, but it is toxic in excess. In humans, excessive dietary NaCl can cause high blood pressure, which contributes to age-related diseases, including stroke and heart disease. We used Caenorhabditis elegans to elucidate how NaCl levels influence animal aging. Most experiments on this animal are conducted in standard culture conditions: Nematode Growth Medium (NGM) agar with a lawn of E. coli. Here, we report that the supplemental NaCl in standard NGM, ∼50 mM, accelerates aging and decreases lifespan. For comparison, we prepared NGM with reduced NaCl or excess NaCl. Considering reduced NaCl as a baseline, wild-type worms on standard NGM displayed normal development and fertility but reduced lifespan and health span, indicating toxicity in old animals. The long-lived mutants daf-2, age-1, and nuo-6, cultured on standard NGM, also displayed reduced lifespan. Thus, NaCl in standard NGM accelerates aging in multiple genetic backgrounds. Wild-type worms on excess NaCl displayed delayed development and reduced fertility, and reduced lifespan and health span, indicating toxicity in both young and old animals. These results suggest that young animals are relatively resistant to NaCl toxicity, but that aging causes progressive sensitivity, such that old animals display toxicity to both standard and excess NaCl. We investigated pathways that respond to NaCl. Young animals cultured with excess NaCl activated gpdh-1, a specific response to NaCl stress. Old animals cultured with excess NaCl activated gpdh-1 and hsp-6, a reporter for the mitochondrial unfolded protein response. Thus, excess NaCl activates multiple stress response pathways in older animals.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876356","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 phenotypic variation of widefins medaka is due to the insertion of a giant transposon containing a viral genome within hoxca cluster.","authors":"Rina Koita, Shunsuke Otake, Natsuki Fukaya, Kenji Yamamoto, Akiteru Maeno, Haruna Kanno, Masaru Matsuda, Akinori Kawamura","doi":"10.1093/genetics/iyaf218","DOIUrl":"https://doi.org/10.1093/genetics/iyaf218","url":null,"abstract":"<p><p>Phenotypic variation in species arises from genetic differences and environmental influences on gene expression. Differences in epigenetic modifications, such as histone modifications and DNA methylation, can also contribute to phenotypic variations, even among individuals with identical genetic information. However, the underlying molecular mechanisms are not yet fully understood, particularly in vertebrates. The number of fin rays in teleosts, such as medaka, serves as a useful model for studying this variation. In a previous study, we demonstrated that the teleost Hox code plays a crucial role in determining the anterior-posterior identity necessary for the formation of dorsal and anal fins. In this study, we investigated widefins medaka, a spontaneous mutant displaying phenotypic variation in the number of dorsal and anal fin rays. Long-read whole-genome sequencing revealed that an extremely large transposon, Teratorn, containing a herpesvirus genome, was inserted into the hoxc12a 3' UTR. This insertion decreased hoxc12a expression and, in some cases, also affected neighboring hox genes, resulting in variations in fin size and the presence or absence of dorsal fins. Additionally, hoxc6a, located 50 kb away from the insertion, was also downregulated in widefins medaka. These findings suggest that this large transposon insertion leads to a reduction in nearby hox gene expression, contributing to the phenotypic variation observed in widefins medaka. These results highlight the role of transposable elements and epigenetic regulation in generating phenotypic diversity in vertebrates.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239991","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":"Correction to: PhaseGen: exact solutions for time-inhomogeneous multivariate coalescent distributions under diverse demographies.","authors":"","doi":"10.1093/genetics/iyaf187","DOIUrl":"https://doi.org/10.1093/genetics/iyaf187","url":null,"abstract":"","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239848","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":"Functional classification of GNAI1 disorder variants in C. elegans uncovers conserved and cell-specific mechanisms of dysfunction.","authors":"Rehab Salama, Eric Peet, Logan Morrione, Sarah Durant, Maxwell Seager, Madison Rennie, Suzanne Scarlata, Inna Nechipurenko","doi":"10.1093/genetics/iyaf216","DOIUrl":"https://doi.org/10.1093/genetics/iyaf216","url":null,"abstract":"<p><p>Heterotrimeric G proteins transduce signals from G protein coupled receptors, which mediate key aspects of neuronal development and function. Mutations in the GNAI1 gene, which encodes Gαi1, cause a disorder characterized by developmental delay, intellectual disability, hypotonia, and epilepsy. However, the mechanistic basis for this disorder remains unknown. Here, we show that GNAI1 is required for ciliogenesis in human cells and use C. elegans as a whole-organism model to determine the functional impact of seven GNAI1-disorder patient variants. Using CRISPR-Cas9 editing in combination with robust cellular (cilia morphology) and behavioral (chemotaxis) assays, we find that T48I, K272R, A328P, and V334E orthologous variants impact both cilia assembly and function in AWC neurons, M88V and I321T have no impact on either phenotype, and D175V exerts neuron-specific effects on cilia-dependent sensory behaviors. Finally, we validate in human ciliated cell lines that D173V, K270R, and A326P GNAI1 variants disrupt ciliary localization of the encoded human Gαi1 proteins similarly to their corresponding orthologous substitutions in the C. elegans ODR-3 (D175V, K272R, and A328P). Overall, our findings determine the in vivo effects of orthologous GNAI1 variants and contribute to mechanistic understanding of GNAI1 disorder pathogenesis as well as neuron-specific roles of ODR-3 in sensory biology.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239966","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":"CrebA regulation of secretory capacity: Genome-wide transcription profiling coupled with in vivo DNA binding studies.","authors":"Dorian J Jackson, Da Peng, Sagarika A Shinde, Ankita Holenarasipura, Vidya Ajay, Patrick Cahan, Deborah J Andrew","doi":"10.1093/genetics/iyaf214","DOIUrl":"https://doi.org/10.1093/genetics/iyaf214","url":null,"abstract":"<p><p>DNA binding assays, expression analyses, and binding site mutagenesis revealed that the Drosophila CrebA transcription factor (TF) boosts secretory capacity in the embryonic salivary gland (SG) through direct regulation of secretory pathway component genes (SPCGs). The mammalian orthologues of CrebA, the Creb3L-family of leucine zipper TFs, not only activate SPCG expression in a variety of mammalian tissues but can also activate SPCG expression in Drosophila embryos, suggesting a highly conserved role for this family of proteins in boosting secretory capacity. However, in vivo assays reveal that CrebA binds far more genes than it regulates, and it remains unclear what distinguishes functional binding. It is also unclear if CrebA is the major factor driving SPCG gene expression in all Drosophila embryonic tissues and/or if CrebA also regulates other tissue-specific functions. Thus, we performed single cell RNA sequencing (scRNA-seq) of CrebA null embryos and compared to scRNA-seq data from existing WT samples to explore the relationship between CrebA binding and gene regulation. We find that CrebA binds the proximal promoters of its targets, that SPCGs are the major class of genes regulated by CrebA across tissues, and that CrebA is sufficient to activate SPCG expression even in cells that do not normally express the protein. A comparison of scRNA-Seq to other methods for capturing regulated transcripts reveals that the different methodologies identify overlapping but distinct sets of CrebA targets.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239936","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":"Correction to: Genomes of the entomopathogenic nematode Steinernema hermaphroditum and its associated bacteria.","authors":"","doi":"10.1093/genetics/iyaf208","DOIUrl":"https://doi.org/10.1093/genetics/iyaf208","url":null,"abstract":"","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239851","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":"Correction to: A model of Hill-Robertson interference caused by purifying selection in a nonrecombining genome.","authors":"","doi":"10.1093/genetics/iyaf186","DOIUrl":"https://doi.org/10.1093/genetics/iyaf186","url":null,"abstract":"","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239897","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":"Mondo: Integrating Disease Terminology Across Communities.","authors":"Nicole A Vasilevsky, Sabrina Toro, Nicolas Matentzoglu, Joseph E Flack, Kathleen R Mullen, Harshad Hegde, Sarah Gehrke, Patricia L Whetzel, Yousif Shwetar, Nomi L Harris, Mee S Ngu, Gioconda L Alyea, Megan S Kane, Paola Roncaglia, Eric Sid, Courtney L Thaxton, Valerie Wood, Roshini S Abraham, Maria Isabel Achatz, Pamela Ajuyah, Joanna S Amberger, Lawrence Babb, Jasmine Baker, James P Balhoff, Jonathan S Berg, Amol Bhalla, Xavier Bofill-De Ros, Ian R Braun, Eleanor C Broeren, Blake K Byer, Alicia B Byrne, Tiffany J Callahan, Leigh C Carmody, Lauren E Chan, Amanda R Clause, Julie S Cohen, Marcello DeLuca, Natalie T Deuitch, May Flowers, Jamie Fraser, Toyofumi Fujiwara, Vanessa Gitau, Jennifer L Goldstein, Dylan Gration, Tudor Groza, Benjamin M Gyori, William Hankey, Jason A Hilton, Daniel S Himmelstein, Stephanie S Hong, Charles T Hoyt, Robert Huether, Eric Hurwitz, Julius O B Jacobsen, Atsuo Kikuchi, Sebastian Köhler, Daniel R Korn, David Lagorce, Bryan J Laraway, Jane Y Li, Adriana J Malheiro, James McLaughlin, Birgit H M Meldal, Shruthi Mohan, Sierra A T Moxon, Monica C Munoz-Torres, Tristan H Nelson, Frank W Nicholas, David Ochoa, Daniel Olson, Tudor I Oprea, Tomiko T Oskotsky, David Osumi-Sutherland, Kelley Paris, Helen E Parkinson, Zoë M Pendlington, Xiao P Peng, Amy Pizzino, Sharon E Plon, Bradford C Powell, Julie C Ratliff, Heidi L Rehm, Lyubov Remennik, Erin R Riggs, Sean Roberts, Peter N Robinson, Justyne E Ross, Kevin Schaper, Brian M Schilder, Johanna L Schmidt, Elliott W Sharp, Morgan N Similuk, Damian Smedley, Tam P Sneddon, Rachel Sparks, Ray Stefancsik, Gregory S Stupp, Shilpa Sundar, Terue Takatsuki, Imke Tammen, Kezang C Tshering, Deepak R Unni, Eloise Valasek, Adeline Vanderver, Alex H Wagner, Ryan F Webb, Danielle Welter, Doron Yaya-Stupp, Andreas Zankl, Xingmin Aaron Zhang, Julie A McMurry, Christopher G Chute, Ada Hamosh, Christopher J Mungall, Melissa A Haendel","doi":"10.1093/genetics/iyaf215","DOIUrl":"https://doi.org/10.1093/genetics/iyaf215","url":null,"abstract":"<p><p>Precision medicine aims to enhance diagnosis, treatment, and prognosis by integrating multimodal data at the point of care. However, challenges arise due to the vast number of diseases, differing methods of classification, and conflicting terminological coding systems and practices used to represent molecular definitions of disease. This lack of interoperability artificially constrains the potential for diagnosis, clinical decision support, care outcome analysis, as well as data linkage across research domains to support the development or repurposing of therapeutics. There is a clear and pressing need for a unified system for managing disease entities ⁠- including identifiers, synonyms, and definitions. To address these issues, we created the Mondo disease ontology-a community-driven, open-source, unified disease classification system that harmonizes diverse terminologies into a consistent, computable framework. Mondo integrates key medical and biomedical terminologies, including Online Mendelian Inheritance in Man (OMIM), Orphanet, Medical Subject Headings (MeSH), National Cancer Institute Thesaurus (NCIt), and more, to provide a comprehensive and accurate representation of disease concepts with fully provenanced and attributed links back to the sources. Mondo can be used as the handle for curation of gene-disease associations utilized in diagnostic applications, research applications such as computational phenotyping, and in clinical coding systems in clinical decision support by pointing the clinician to the numerous knowledge resources linked to the Mondo identifier. Mondo's community-centric approach, stewarded by the Monarch Initiative's expertise in ontologies, ensures that the ontology remains adaptable to the evolving needs of biomedical research and clinical communities, as well as the knowledge providers.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239994","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}