Genetics最新文献_第7页

Quantile-specific confounding: correction for subtle population stratification via quantile regression. 分位数特异性混淆：通过分位数回归对细微人群分层进行校正。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf138

Chen Wang, Marco Masala, Edoardo Fiorillo, Marcella Devoto, Francesco Cucca, Iuliana Ionita-Laza

引用次数: 0

Mutational analysis of the Drosophila CMG helicase reveals relationships among chromosome integrity and the maintenance of spindle and centrosome structure. 果蝇CMG解旋酶的突变分析揭示了染色体完整性与纺锤体和中心体结构维持之间的关系。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf124

Lucia Graziadio, Livia Scatolini, Elisabetta Bucciarelli, Grazia Daniela Raffa, Silvia Bonaccorsi, Maurizio Gatti

{"title":"Mutational analysis of the Drosophila CMG helicase reveals relationships among chromosome integrity and the maintenance of spindle and centrosome structure.","authors":"Lucia Graziadio, Livia Scatolini, Elisabetta Bucciarelli, Grazia Daniela Raffa, Silvia Bonaccorsi, Maurizio Gatti","doi":"10.1093/genetics/iyaf124","DOIUrl":"10.1093/genetics/iyaf124","url":null,"abstract":"The CMG (Cdc45-MCM-GINS) complex is a conserved helicase that plays an essential DNA unwinding function at replication forks. Here, we analyzed the mitotic phenotypes caused in Drosophila by knockdown of Cdc45, Mcm5, and the four GINS genes (Sld5, Psf1, Psf2, and Psf3). Silencing of these genes resulted in virtually identical mitotic phenotypes. Brain cells from mutant and RNAi larvae showed severe defects in chromosome condensation, chromosome breakage, and frequent polyploid mitotic figures. In addition, mutant cells showed reduced Cid (Cenp-A) incorporation at centromeres and strong alterations in spindle and centrosome structures. Our cytological and genetic analyses suggest that replication-related DNA damage and Cid-dependent centromere/kinetochore defects trigger the spindle assembly checkpoint (SAC) that arrests the cells in a prometaphase-like stage. The arrested cells undergo mitotic slippage accompanied by Cyclin B degradation and eventually return to G1 giving rise to polyploid cells. Our analyses further suggest that during the prolonged prometaphase arrest both the centrosomes and the spindles undergo severe structural degeneration and that the spindle defects are not the consequence of the aberrant centrosome behavior. Most studies on mitotic slippage have been carried out in cells exposed to anti-microtubule agents and could not address the behavior of the spindle. Conversely, our results illuminate the complex consequences of replication stress and reveal what happens to the mitotic apparatus during the prolonged spindle assembly checkpoint-induced mitotic arrest. Because prolonged mitosis is a common event in human cancers, our results could provide useful information for studies on cancer etiology and therapy.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512629","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}

引用次数: 0

Translation regulation promotes stress adaptation in the human fungal pathogen Candida glabrata. 翻译调节促进人类真菌病原体念珠菌的应激适应。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf134

Aishwarya Rana, Anil Thakur

{"title":"Translation regulation promotes stress adaptation in the human fungal pathogen Candida glabrata.","authors":"Aishwarya Rana, Anil Thakur","doi":"10.1093/genetics/iyaf134","DOIUrl":"10.1093/genetics/iyaf134","url":null,"abstract":"Invasive candidiasis presents a significant healthcare challenge. The human opportunistic fungal pathogen Candida glabrata, a cause of mucosal and deep-seated infections, resists key antifungal drugs and rapidly proliferates within host macrophages, where it withstands high oxidative stress and amino acid starvation. Unlike C. albicans, C. glabrata lacks true hyphae and relies more on stress adaptation mechanisms than filamentation for virulence. This study explores the molecular mechanisms underlying stress adaptations in C. glabrata that contribute to its pathogenicity. Our findings revealed that C. glabrata survives oxidative stress and amino acid starvation more effectively than Saccharomyces cerevisiae, C. albicans, and C. auris. We observed that amino acid starvation and oxidative stress downregulate global protein translation through Gcn2-mediated eukaryotic initiation factor 2α phosphorylation, enabling adaptive recovery and activating the transcription factor Gcn4. The gcn2Δ and gcn4Δ mutants had impaired growth under stress conditions, highlighting the pivotal role of Gcn2-Gcn4 in regulating stress-specific transcripts and promoting fungal survival. Transcriptome sequencing under amino acid starvation conditions demonstrated that Gcn4 orchestrates the expression of a broad array of genes, primarily those involved in stress responses, which are essential for survival during nutrient deprivation. Notably, under oxidative stress, Gcn4 adopts unique adaptation strategies by upregulating a core set of oxidative stress-responsive genes by coordinating a more specialized transcriptional response tailored to oxidative stress. Additionally, gcn2Δ and gcn4Δ exhibited elevated levels of reactive oxygen species and defective replication within host macrophages, with Gcn4 being crucial in host survival and virulence. This study underscores the importance of translational regulation in stress adaptation of C. glabrata.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660860","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}

引用次数: 0

Drug screens using the nematode Caenorhabditis elegans. 利用秀丽隐杆线虫进行药物筛选。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf141

Peter J Roy

引用次数: 0

Alleles of Chaser, a dominant modifier of the Drosophila melanogaster foraging gene, are consistent with variegating alleles of the heterochromatic gene spookier. 黑腹果蝇觅食基因的显性修饰基因Chaser的等位基因与异色基因spookier的变异等位基因一致。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf123

Alistair B Coulthard, Richard Yuditskiy, Alexander R Molnar, Qaim Ali Ramazan, Marla B Sokolowski, Arthur J Hilliker

{"title":"Alleles of Chaser, a dominant modifier of the Drosophila melanogaster foraging gene, are consistent with variegating alleles of the heterochromatic gene spookier.","authors":"Alistair B Coulthard, Richard Yuditskiy, Alexander R Molnar, Qaim Ali Ramazan, Marla B Sokolowski, Arthur J Hilliker","doi":"10.1093/genetics/iyaf123","DOIUrl":"10.1093/genetics/iyaf123","url":null,"abstract":"The relationship between genes and quantitative behavioral traits involves complex regulatory networks. Identifying genes that operate in these regulatory pathways can be challenging, especially when dealing with dominant genetic factors. Our work has focused on a naturally occurring behavioral polymorphism in larval foraging behavior in Drosophila melanogaster. This polymorphism in larval foraging behavior arises from variation in the foraging (for) gene with its rover and sitter naturally occurring variants. The dominant rover allele (forR) results in larvae which move longer distances while foraging compared with larvae with the recessive sitter (fors) alleles. In this article, we report the successful mapping of the Chaser (Csr) gene, a dominant modifier of larval foraging behavior which makes sitter larvae behave in a rover-like manner. We localized Csr by first mapping recessive phenotype tags closely linked to Csr. These phenotype tags mapped to the centromeric heterochromatin on the right arm of chromosome 3. We showed through a combination of deletion mapping, qRT-PCR and feeding of ecdysone hormone to larvae during development that the alleles of Csr are consistent with variegating alleles of the gene spookier (spok). With spok being an essential gene in the synthesis of the molting hormone ecdysone, we have established a link between ecdysone signaling and larval foraging behavior in D. melanogaster.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508946","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}

引用次数: 0

Long telomere inheritance through budding yeast sexual cycles. 芽殖酵母性周期中的长端粒遗传。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf129

Vasilisa Sidarava, Sarah Mearns, David Lydall

{"title":"Long telomere inheritance through budding yeast sexual cycles.","authors":"Vasilisa Sidarava, Sarah Mearns, David Lydall","doi":"10.1093/genetics/iyaf129","DOIUrl":"10.1093/genetics/iyaf129","url":null,"abstract":"The ends of linear eukaryotic chromosomes are protected from being recognized as DNA double-strand breaks by telomeres, containing repetitive DNA sequences that bind specific proteins. In humans, mutations in telomere regulatory genes lead to short or long telomere syndromes. These syndromes often show genetic anticipation, where the disease has an earlier onset and a more severe manifestation in each new generation. Later generations inherit not only the mutation affecting telomere length, but also abnormal telomere length. Many aspects of telomere length homeostasis are conserved between mammals and yeast. Here, we explored telomere length inheritance patterns through the sexual cycle in yeast. Analysis of single telomeres, rather than bulk telomeres, shows that if haploid yeast with short telomeres mate with wild-type yeast, creating diploids, short telomere lengths rapidly normalize (within 30 cell divisions). However, long telomeres inherited from one parent can persist for more than 200 mitotic cell divisions. Long telomeres can also be transmitted through more than one round of meiosis, independently of mutations that cause long telomeres. These patterns, along with haploinsufficiency effects, show that even in yeast, there is a complex relationship between telomere length, telomere length inheritance, and mutations that affect telomere length. Our findings may have implications for families affected by telomere syndromes.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638518","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}

引用次数: 0

Excretory gland cell and NSPC genes in C. elegans: investigating their physiological roles. 秀丽隐杆线虫分泌腺细胞和NSPC基因的生理作用研究。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf125

Zuzanna Mackiewicz, Vladyslava Liudkovska, Andrzej Dziembowski

{"title":"Excretory gland cell and NSPC genes in C. elegans: investigating their physiological roles.","authors":"Zuzanna Mackiewicz, Vladyslava Liudkovska, Andrzej Dziembowski","doi":"10.1093/genetics/iyaf125","DOIUrl":"10.1093/genetics/iyaf125","url":null,"abstract":"The nematode Caenorhabditis elegans is one of the best-studied model organisms in molecular biology; however, many aspects of its physiology and the functions of many genes remain poorly understood. In this study, we investigated the role of Nematode-Specific Peptide Family, group C (NSPC) proteins, whose mRNAs were recently identified as primary targets of the poly(A) polymerase TENT-5. Surprisingly, we found that NSPCs are exclusively expressed in the excretory gland cell, a cell with still unclear functionality. Using an optogenetic approach, we precisely ablated the excretory gland cell and observed that, apart from a strong downregulation of NSPCs, nematodes exhibited no transcriptomic or physiological changes in its absence. Additionally, we generated and thoroughly studied a strain with a deletion of all 18 nspc genes, which revealed that, despite previous indications, NSPCs do not influence the worm's defense response. Instead, the transcriptomic analysis showed that the absence of NSPCs results in gene expression changes resembling those observed for DAF-16 mutants, suggesting that NSPCs may somehow influence the key C. elegans insulin signaling pathway. Although further studies are required to explain the exact genetic interaction and elucidate its physiological effects, our findings provide new insights into this unexplored part of nematode physiology.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627454","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}

引用次数: 0

Analysis of a BCOR internal tandem duplication in mouse embryonic stem cell to neuronal precursor differentiation. BCOR内串联复制在小鼠胚胎干细胞向神经元前体细胞分化中的作用分析。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf133

Zuzer Dhoondia, Hyuckjoon Kang, Kwangwoon Lee, Philip A Cole, Mitzi I Kuroda

{"title":"Analysis of a BCOR internal tandem duplication in mouse embryonic stem cell to neuronal precursor differentiation.","authors":"Zuzer Dhoondia, Hyuckjoon Kang, Kwangwoon Lee, Philip A Cole, Mitzi I Kuroda","doi":"10.1093/genetics/iyaf133","DOIUrl":"10.1093/genetics/iyaf133","url":null,"abstract":"BCOR (BCL-6 corepressor) is a component of variant Polycomb Repressive Complex 1.1 (vPRC1.1), one of several vPRC1 complexes that catalyze histone H2A ubiquitination thought to play an important role in PRC2 binding and the deposition of H3K27me3 to silence genes. The PCGF Ub-like fold discriminator (PUFD) domain at the C-terminus of BCOR forms a heterodimer with PCGF1, serving as a critical interface for its polycomb-dependent functions. Internal tandem duplication (ITD) mutations in BCOR, causing in-frame duplications of 20 to 40 amino acids in the PUFD domain, are observed in heterogeneous tumors including sarcomas (kidney, bone, and endometrium) and neuroepithelial tumors in the brain. To dissect the molecular mechanisms underlying aberrant function of BCOR-ITD mutants, we employed mouse embryonic stem (mES) cells expressing either transgenic or endogenous BCOR-ITD. Our results indicate that the BCOR-ITD mutation does not disrupt the BCOR-PCGF1 interaction, instead maintaining the integrity of the vPRC1.1 complex. While displaying subtle changes in imprinted gene expression during differentiation toward a neural lineage, BCOR-ITD mutants also had no growth phenotype in culture. Furthermore, we found that CD24+ cells were enriched, as expected, during neural progenitor differentiation in both wildtype and mutant cells. However, sensitization of BCOR-ITD mES cells with EZH2 inhibitor during differentiation resulted in an unexpected enrichment of a CD24+CD26+ subpopulation, indicating aberrant cell fate that was also prevalent in a BCOR truncation mutant. Together, our results suggest that BCOR-ITD may largely retain wildtype function, but with increased susceptibility to synergistic stress on the Polycomb pathway.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620966","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}

引用次数: 0

The genetic architecture of quantitative variation in the self-incompatibility response within Phlox drummondii (Polemoniaceae). 竹节夹竹桃自交不亲和反应数量变异的遗传结构。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf132

Grace A Burgin, Federico Roda, Matthew Farnitano, Charles Hale, Antonio Serrato-Capuchina, Robin Hopkins

{"title":"The genetic architecture of quantitative variation in the self-incompatibility response within Phlox drummondii (Polemoniaceae).","authors":"Grace A Burgin, Federico Roda, Matthew Farnitano, Charles Hale, Antonio Serrato-Capuchina, Robin Hopkins","doi":"10.1093/genetics/iyaf132","DOIUrl":"10.1093/genetics/iyaf132","url":null,"abstract":"Flowering plants display extensive variation in selfing rate, a trait with significant ecological and evolutionary consequences. Many species use genetic mechanisms to recognize and reject self-pollen (termed self-incompatibility or SI), and the loss of SI is one of the most common evolutionary transitions among flowering plants. Despite the ubiquity of transitions to self-compatibility (SC), little is known about the genetic architecture through which SC evolves. Specifically, it is important to determine if SC has a simple or polygenic basis and if variation localizes to the self-pollen recognition locus (the \"S-locus\"). Phlox drummondii (Polemoniaceae) is a model system for exploring mating system evolution and expresses range-wide variation in SI. Here, we investigate the genetic architecture of SC variants segregating within this otherwise SI species. Using multiple independent crosses, we uncover numerous QTLs associated with intraspecific SI variation, consistent with a polygenic genetic architecture. While some QTLs overlap across mapping experiments, other QTLs are unique, suggesting that multiple genetic routes to SC exist. We demonstrate that P. drummondii has a sporophytic SI system, revealing an independent evolution of SI within the Phlox lineage. We map this novel S-locus and find that the genomic region containing the S-locus is associated with intraspecific variation in SI in one of the 3 mapping populations. Although further work is necessary to clarify the conditions under which quantitative variation in SI represents a transitional pathway to complete SC, our study reveals the genetic architecture upon which selection could act to drive this frequent and evolutionarily significant transition.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627455","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}

引用次数: 0

Functional analysis of human EED variants using Drosophila. 果蝇对人类EED变异的功能分析。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf120

Sharri S Cyrus, Sònia Medina-Giró, Tianshun Lian, Douglas W Allan, William T Gibson

引用次数: 0