Genetics最新文献

{"title":"Clade Distillation for Genome-wide Association Studies.","authors":"Ryan Christ, Xinxin Wang, Louis J M Aslett, David Steinsaltz, Ira Hall","doi":"10.1093/genetics/iyaf158","DOIUrl":"https://doi.org/10.1093/genetics/iyaf158","url":null,"abstract":"<p><p>Testing inferred haplotype genealogies for association with phenotypes has been a longstanding goal in human genetics given their potential to detect association signals driven by allelic heterogeneity - when multiple causal variants modulate a phenotype - in both coding and noncoding regions. Recent scalable methods for inferring locus-specific genealogical trees along the genome, or representations thereof, have made substantial progress towards this goal; however, the problem of testing these trees for association with phenotypes has remained unsolved due to the growth in the number of clades with increasing sample size. To address this issue, we introduce several practical improvements to the kalis ancestry inference engine, including a general optimal checkpointing algorithm for decoding hidden Markov models, thereby enabling efficient genome-wide analyses. We then propose LOCATER, a powerful new procedure based on the recently proposed Stable Distillation framework, to test local tree representations for trait association. Although LOCATER is demonstrated here in conjunction with kalis, it may be used for testing output from any ancestry inference engine, regardless of whether such engines return discrete tree structures, relatedness matrices, or some combination of the two at each locus. Using simulated quantitative phenotypes, our results indicate that LOCATER achieves substantial power gains over traditional single marker testing, ARG-Needle, and window-based testing in cases of allelic heterogeneity, while also improving causal region localization. These findings suggest that genealogy-based association testing will be a fruitful approach for gene discovery, especially for signals driven by multiple ultra-rare variants.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838346","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":"Combining ability of banana triploid hybrid progenitors and genomic prediction of cross performance for agro-morphological traits.","authors":"Lucile Toniutti, Simon Rio, Camille Madec, Sébastien Ricci, Chantal Guiougou, Franck Marius, Claude Mina, Jean-Marie Eric Delos, Frédéric Lambert, Jean-Claude Efile, Angélique D'Hont, Guillaume Martin, Jean-Yves Hoarau, Frédéric Salmon","doi":"10.1093/genetics/iyaf119","DOIUrl":"10.1093/genetics/iyaf119","url":null,"abstract":"<p><p>Breeding disease-resistant cultivars that meet commercial criteria is essential to sustain banana production threatened by major diseases. Edible bananas are seedless triploid hybrids that represent end-breeding products. Hence, the crucial step in banana breeding is to improve and combine the parents. Currently, little information is available on parental combining abilities and on the inheritance of major traits to effectively guide banana breeding strategies. In this study, a breeding population of 2,723 triploid individuals resulting from multiparental diploid-tetraploid crosses was characterized during three crop cycles for 23 traits relating to plant and fruit architecture and bunch yield components. The phenotypic variance was partitioned between non-genetic and genetic effects, the latter including the general combining ability of diploid and tetraploid parents, their specific combining ability, and additional variance due to the within-cross genetic variability. Heritability was moderate to high depending on the trait and revealed the predominance of the tetraploid parent's contribution to hybrid performance for most traits. The use of parental genomic information enabled cross-mean performance prediction through genomic relationship matrices of general and specific combining abilities, the latter being partitioned into dominance and across-population epistasis contributions. Predictive abilities often greater than 0.5 were obtained, particularly when the tetraploid parent was observed in other crosses and, for some traits, when neither parent was observed. Information on trait inheritance and genomic prediction of cross-mean performance will help in selecting and combining parents, facilitating the identification of promising hybrids.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334210","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":"Analysis of combinatorial cohesin subunit gene deletions in budding yeast.","authors":"Grace Duke, Robert V Skibbens","doi":"10.1093/genetics/iyaf107","DOIUrl":"10.1093/genetics/iyaf107","url":null,"abstract":"<p><p>Throughout the cell cycle, DNA molecules convert between hierarchical intramolecular (cis) and intermolecular (trans) associations. Cohesin ATPase complexes produce both types of DNA associations which collectively are required for sister chromatid segregation, chromatin condensation, genomic architecture, gene transcription, and DNA repair. The mechanisms that regulate cohesin cis- and trans-activities, however, remain controversial. A popular model is that a regulatory complex (Pds5, Irr1/Scc3, and Rad61) sits atop a core ring-like complex (Mcd1/Scc1, Smc1, and Smc3), the latter of which exhibits the inherent ATPase activities responsible for producing cis- and trans-DNA conformations. Additional proteins transiently interact with cohesins to promote cohesin deposition onto DNA (Scc2 and Scc4) or stabilize cohesin-DNA binding (Eco1/Ctf7). Of these 9 components, only RAD61 is nonessential. Recent findings, however, identified pairs of suppressor mutations that support the viability of cells individually deleted for either PDS5 or ECO1/CTF7 (herein ECO1). Intriguingly, CLN2 deletion is common in both suppressor pairs, suggesting that combined suppressor mutations may support the viability of cells co-deleted for both ECO1 and PDS5. These results further suggest that the addition of other suppressor mutations (such as ELG1 and RAD61) may support the viability of cells deleted of all auxiliary subunits-including IRR1/SCC3 (herein SCC3). Here, we test these predictions and report on novel gene deletion combinations required for cell cycle progression and cell viability.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259131","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":"Toward more sustainable research: reducing the environmental impact when working with Drosophila.","authors":"Milo Challiner, Saroj Saurya, Sanjai Patel, Jordan W Raff, Maggy Fostier, Andreas Prokop","doi":"10.1093/genetics/iyaf114","DOIUrl":"10.1093/genetics/iyaf114","url":null,"abstract":"<p><p>The ever-increasing amounts of plastic waste and greenhouse gas emissions worldwide threaten our environment. Biomedical laboratories across the world generate serious amounts of plastic waste often disposed of via high-emission strategies. Achieving sustainability is imperative but requires awareness and knowledge of the regulations, available options, and their implications. To illustrate the thought processes involved, we showcase the Manchester Fly Facility which supports work with the genetic model organism Drosophila and serves 13 research groups. In 2022, we estimated ∼4 tonnes of \"clinical\" waste generation by the facility enriched with single-use polystyrene plastic containers, all frozen for 2 days and then incinerated. We calculate the resulting environmental and economic costs and compare them to practices reported to us from other fly facilities worldwide. We then discuss feasible management options, separately explaining alternative choices for (1) container materials, (2) the processing of genetically modified organisms, (3) re-use strategies, and (4) waste management procedures. This information hopefully raises awareness and understanding to incentivize laboratories worldwide to adopt more sustainable choices, as is permitted by their local infrastructure and regulations. To illustrate what can be achieved, we extrapolate the Manchester data from 2022 to a period of 10 years and calculate the impact of different management strategies, indicating that up to 80% of greenhouse gas emissions and 76% of plastic waste can be saved. The resulting economic savings are of further benefit and could be re-invested to pay for additional workforce, which may otherwise pose an important barrier to re-use scenarios in many countries.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286932","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":"Efficient epistasis inference via higher-order covariance matrix factorization.","authors":"Kai S Shimagaki, John P Barton","doi":"10.1093/genetics/iyaf118","DOIUrl":"10.1093/genetics/iyaf118","url":null,"abstract":"<p><p>Epistasis can profoundly influence evolutionary dynamics. Temporal genetic data, consisting of sequences sampled repeatedly from a population over time, provides a unique resource to understand how epistasis shapes evolution. However, detecting epistatic interactions from sequence data is technically challenging. Existing methods for identifying epistasis are computationally demanding, limiting their applicability to real-world data. Here, we present a novel computational method for inferring epistasis that substantially reduces computational costs without sacrificing accuracy. We validated our approach in simulations and applied it to study HIV-1 evolution over multiple years in a data set of 16 individuals. There we observed a strong excess of negative epistatic interactions between beneficial mutations, especially mutations involved in immune escape. Our method is general and could be used to characterize epistasis in other large data sets.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337165","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 rapid accurate approach to inferring pedigrees in endogamous populations.","authors":"Cole M Williams, Brooke A Scelza, Sarah D Slack, Neus Font-Porterias, Dana R Al-Hindi, Rasika A Mathias, Harold Watson, Kathleen C Barnes, Ethan Lange, Randi K Johnson, Christopher R Gignoux, Sohini Ramachandran, Brenna M Henn","doi":"10.1093/genetics/iyaf094","DOIUrl":"10.1093/genetics/iyaf094","url":null,"abstract":"<p><p>Accurate reconstruction of pedigrees from genetic data remains a challenging problem. Many relationship categories (e.g. half-sibships vs avuncular) can be difficult to distinguish without external information. Pedigree inference algorithms are often trained on European-descent families in urban locations. Thus, existing methods tend to perform poorly in endogamous populations for which there may be reticulations within the pedigrees and elevated haplotype sharing. We present a simple, rapid algorithm which initially uses only high-confidence first-degree relationships to seed a machine learning step based on summary statistics of identity-by-descent sharing. One of these statistics, our \"haplotype score,\" is novel and can be used to: (1) distinguish half-sibling pairs from avuncular or grandparent-grandchildren pairs; and (2) assign individuals to ancestor vs descendant generation. We test our approach in a sample of 700 individuals from northern Namibia, sampled from an endogamous population called the Himba. Due to a culture of concurrent relationships in the Himba, there is a high proportion of half-sibships. We accurately identify first through fourth-degree relationships and distinguish between various second-degree relationships: half-sibships, avuncular pairs, and grandparent-grandchildren. We further validate our approach in a second African-descent dataset, the Barbados Asthma Genetics Study, and a European-descent founder population from Quebec. Accurate reconstruction of relatives facilitates estimation of allele frequencies, tracing allele trajectories, improved phasing, heritability and other population genomic questions.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112497","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":"Genetic analysis of stress hormone levels in hair of healthy nursery pigs and their relationships with backtest responses.","authors":"Fazhir Kayondo, Hayder Al-Shanoon, Yolande M Seddon, Dylan Carette, Carmen Cole, David M Janz, Frederic Fortin, John C S Harding, Michael K Dyck, Graham S Plastow, PigGen Canada, Jack C M Dekkers","doi":"10.1093/genetics/iyaf092","DOIUrl":"10.1093/genetics/iyaf092","url":null,"abstract":"<p><p>This study explored the genetics of the levels of stress hormones (cortisol, cortisone, DHEA, and DHEA-S) in hair of 863 clinically healthy Yorkshire × Landrace male pigs at ∼40 days of age and evaluated their potential as biomarkers of innate stress response by estimating genetic correlations with responses to a 30 s backtest performed at ∼27 days of age. Backtest responses included the number and intensity of vocalizations (VN and VI) and struggles (SN and SI). With pigs genotyped using a 50 K single nucleotide polymorphism (SNP) panel that was imputed to 650 K SNPs, heritability estimates for the levels of cortisol, cortisone, DHEA, and DHEA-S were 0.33, 0.04, 0, and 0.31, respectively, while those for backtest responses ranged from 0.26 to 0.57. Litter effects accounted for 9 to 16% of the phenotypic variance for stress hormone levels and none for backtest responses. Genetic correlation estimates among stress hormone levels were strongest between cortisol and cortisone (0.99 ± 0.12), while those among backtest responses ranged from 0.60 to 0.99. Cortisol was estimated to have moderate genetic correlations with VN (0.24 ± 0.19) and VI (0.50 ± 0.24) but not with SN and SI. Genome-wide association studies identified a major quantitative trait locus (QTL) for hair cortisol levels near the glucocorticoid receptor gene (NR3C1) that explained 45.3% of the genetic variance and that may be different than a causative mutation that was previously identified in this gene for cortisol levels in porcine blood. An extra copy of the minor allele (frequency = 9%) at the lead SNP for this QTL, rs341258564 originated from both parental breeds and reduced levels of cortisol by 30 ± 6% and of cortisone by 17 ± 4%, and increased VN by 5 ± 2%. Additional QTL with smaller effects (1.0 to 11.1% of genetic variance) were identified for DHEA-S, cortisol/DHEA-S, cortisone/DHEA-S, VI, and VN. Ranked gene set enrichment analyses of 0.25 Mb windows based on genetic variance explained showed that windows associated with glucocorticoid levels were enriched for biological terms related to energy production and suppression of inflammation. In contrast, those associated with DHEA-S were enriched for biological processes related to immunity activation and gene transcriptional and post-transcriptional regulation. These findings establish the genetic basis of stress response in young and clinically healthy pigs, identify the genomic location of a major QTL for hair cortisol levels, and show that cortisol levels in hair of young and healthy pigs are potential genetic biomarkers for the innate coping response style of pigs to noninfectious stressors. These results open avenues that can facilitate selection of pigs that cope better with noninfectious stressors.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081453","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":"Mentorship and acts of kindness.","authors":"Brandon S Gaut","doi":"10.1093/genetics/iyaf105","DOIUrl":"10.1093/genetics/iyaf105","url":null,"abstract":"<p><p>As the inaugural recipient of the Genetics Society of America Mentorship Award, Gaut is being recognized for the mentorship of PhD students and postdocs in his lab and for being a dedicated advocate for mentees as an administrator at University of California, Irvine and as president of SMBE where he helped implement an impactful child support policy for conferences. This award also recognizes Gaut's commitment to fostering an inclusive environment and work-life balance for his students.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477529","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 unified framework governing the establishment and maintenance of transgenerational epigenetic inheritance.","authors":"Rachel M Woodhouse, Natalya Frolows, Dhruv S Monteiro, Jessica J Hawes, Azelle Hawdon, Michael Davies, Owen Watson, Victoria S Lennox, Alyson Ashe","doi":"10.1093/genetics/iyaf106","DOIUrl":"10.1093/genetics/iyaf106","url":null,"abstract":"<p><p>Transgenerational epigenetic inheritance (TEI) is the transfer of nongenetic information between generations. In Caenorhabditis elegans, RNA interference (RNAi) is a conserved process initiated by double-stranded RNA, which can induce TEI. While many factors have been implicated in TEI, whether they act in establishment or maintenance of the transgenerational signal, and the generation in which they act, has not been defined. Here, we characterize the actions of glh-1, hrde-1, -2, -4, morc-1, nrde-1, -2, -4, set-25, -32, wago-1, -4, znfx-1, pup-1, and emb-4 within RNAi-induced TEI. We show that these genes can be classified into 3 groups: those involved in only establishment or maintenance, or those involved in both. We identify a heterochromatin-based pathway established in the P0 generation by histone methyltransferases and maintained in later generations by MORC-1, upstream of HRDE-1-dependent silencing. By investigating lineage dynamics, we provide evidence that inheritance patterns are partially determined in RNAi-exposed parents, but that variation between offspring also contributes. And finally, we demonstrate that polyUG RNAs broadly correlate with, but do not define, inheritance patterns. Together, this work forms a cohesive model of RNAi-induced TEI.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217348","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":"Harnessing Microbial Tools: Escherichia coli as a Vehicle for Neuropeptide Functional Analysis in Caenorhabditis elegans.","authors":"Elizabeth M DiLoreto, Shruti Shastry, Emily J Leptich, Douglas K Reilly, Rachel N Arey, Jagan Srinivasan","doi":"10.1093/genetics/iyaf155","DOIUrl":"10.1093/genetics/iyaf155","url":null,"abstract":"<p><p>Animals respond to changes in their environment and internal states via neuromodulation. Neuropeptides modulate neural circuits with flexibility because one gene can produce either multiple copies of the same neuropeptide or different neuropeptides. However, with this architectural complexity, the function of discrete and active neuropeptides is muddled. Here, we design a genetic tool that facilitates functional analysis of individual peptides. We engineered Escherichia  coli bacteria to express active peptides, fed loss-of-function Caenorhabditis elegans, and rescued the activity of genes with varying lengths and functions: pdf-1, flp-3, ins-6, and ins-22. Some peptides were functionally redundant, while others exhibit unique and previously uncharacterized functions. We postulate our rescue-by-feeding approach can elucidate the functional landscape of neuropeptides, identifying the circuits and complex peptidergic pathways that regulate different behavioral and physiological processes.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144838350","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}