Featured
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Article
| Open AccessWhole genomes from Angola and Mozambique inform about the origins and dispersals of major African migrations
African human genome variation remains under-sampled. Here, the authors present a collection of 350 whole genome sequences from Angola and Mozambique and model the timing and extent of significant demographic events in African history.
- Sam Tallman
- , Maria das Dores Sungo
- & Sandra Beleza
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Article
| Open AccessSMARCB1 loss activates patient-specific distal oncogenic enhancers in malignant rhabdoid tumors
The regulatory landscape of malignant rhabdoid tumor (MRT) due to SMARCB1 loss remains to be explored. Here, the authors perform multi-omics analysis using patient-derived MRT organoids and characterise the epigenetic reprogramming events underlying SMARCB1 loss.
- Ning Qing Liu
- , Irene Paassen
- & Jarno Drost
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Article
| Open AccessSoybean reduced internode 1 determines internode length and improves grain yield at dense planting
Many cereal crops have been bred to be more compact to allow high-density planting, but soybean has remained relatively overlooked. Here, the authors describe a compact soybean mutant, reduced internode 1, that significantly enhances grain yield under high-density planting conditions compared to an elite cultivar.
- Shichen Li
- , Zhihui Sun
- & Sijia Lu
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Article
| Open AccessHaplotype-based inference of recent effective population size in modern and ancient DNA samples
The authors introduce a new computational method, HapNe, for inferring the recent effective size of human populations. HapNe does not require high-quality genotype data, making it suitable for the study of ancient DNA samples.
- Romain Fournier
- , Zoi Tsangalidou
- & Pier Francesco Palamara
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Article
| Open AccessBuilding a eukaryotic chromosome arm by de novo design and synthesis
In Saccharomyces cerevisiae, the left arm of chromosome XII only requires 12 genes to maintain cell viability, whereas 25 genes are needed for robust fitness. Here the authors demonstrate that the entire arm can be replaced by a neochromosome with completely artificial sequences.
- Shuangying Jiang
- , Zhouqing Luo
- & Junbiao Dai
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Article
| Open AccessStrong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease
African Americans have an elevated risk of developing chronic kidney disease, yet only a fraction of those with high-risk genotypes develop the disease. Here, the authors show that a missense variant in APOL1 has a strong protective effect when co-inherited with the high-risk G2 allele of APOL1, with important implications for clinical practice and translational research.
- Yask Gupta
- , David J. Friedman
- & Simone Sanna-Cherchi
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Article
| Open AccessUtilizing river and wastewater as a SARS-CoV-2 surveillance tool in settings with limited formal sewage systems
COVID-19 has impacted health systems unequally and widespread SARS-CoV-2 testing for community surveillance has been limited globally. This work in Malawi highlights how river and wastewater can be used to detect emerging SARS-CoV-2 waves, identify variants of concern, and provide an early warning system.
- Kayla G. Barnes
- , Joshua I. Levy
- & Nicholas Feasey
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Article
| Open AccessCell-type-specific Alzheimer’s disease polygenic risk scores are associated with distinct disease processes in Alzheimer’s disease
Alzheimer’s disease genetic risk is enriched in glial genes. Here, the authors derive cell-type-specific polygenic risk scores and link astrocytic genes with Aβ, and microglial genes with Aβ, tau, microglial activation, and cognitive decline.
- Hyun-Sik Yang
- , Ling Teng
- & Reisa A. Sperling
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Article
| Open AccessThe SPOC proteins DIDO3 and PHF3 co-regulate gene expression and neuronal differentiation
Death-inducer obliterator 3 (DIDO3) and PHD finger protein 3 (PHF3) are paralogue proteins that regulate transcription elongation by docking onto phosphorylated serine-2 in the C-terminal domain (CTD) of Pol II through their SPOC domains. Here the authors characterize the interplay of these proteins and show that they coregulate neuronal target genes.
- Johannes Benedum
- , Vedran Franke
- & Dea Slade
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Article
| Open AccessDominance in self-compatibility between subgenomes of allopolyploid Arabidopsis kamchatica shown by transgenic restoration of self-incompatibility
Self-incompatibility in diploid Arabidopsis relatives is determined by a dominance relationship that is epigenetically regulated. Using transgenic methods, this study demonstrates that the dominance relationship between subgenomes of the allopolyploid species Arabidopsis kamchatica underlies it’s self-compatibility.
- Chow-Lih Yew
- , Takashi Tsuchimatsu
- & Kentaro K. Shimizu
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Article
| Open AccessLocal adaptation and future climate vulnerability in a wild rodent
A species’ response to anthropogenic climate change may depend on its adaptations to past climate changes. Here, the authors use whole-genome resequencing and genetic-environment association to identify genes important for local adaptation and project adaptation under future climate scenarios across bank vole populations in Britain.
- Silvia Marková
- , Hayley C. Lanier
- & Petr Kotlík
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Article
| Open AccessHDAC8-mediated inhibition of EP300 drives a transcriptional state that increases melanoma brain metastasis
The drivers of melanoma brain metastases (MBM) remain poorly understood. Here, the authors identify stress-induced HDAC8 activity as the driver of a neural crest-stem cell like transcriptional state that leads to MBM, and explore the molecular mechanism that drives this transition.
- Michael F. Emmons
- , Richard L. Bennett
- & Keiran S. M. Smalley
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Article
| Open AccessGlobal genetic diversity, introgression, and evolutionary adaptation of indicine cattle revealed by whole genome sequencing
Indicine cattle make up half of all cattle populations worldwide. Using a large genomic dataset, this study finds historic migrations and extensive introgression with domestic and wild bovine species has facilitated this species physiological adaptation to extreme environments.
- Ningbo Chen
- , Xiaoting Xia
- & Chuzhao Lei
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Article
| Open AccessOVOL2 sustains postnatal thymic epithelial cell identity
The molecular mechanisms that maintain thymic epithelial cell (TEC) identity throughout life are incompletely understood. Here, the authors demonstrate that the transcription factor, Ovol2, maintains post-natal TECs by preventing their epithelial-to-mesenchymal transition.
- Xue Zhong
- , Nagesh Peddada
- & Bruce Beutler
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Article
| Open AccessDNA polymerase ε harmonizes topological states and R-loops formation to maintain genome integrity in Arabidopsis
Here the authors show that Inhibition of DNA topoisomerase 1 (TOP1i) increases the defects in root growth of a DNA damage repair-compromised mutant atm. They identify a mutant DNA polymerase ε (POL2A) which rescues the sensitivity of atm to TOP1i by modulating R-loops dynamics near DNA replication origins.
- Qin Li
- , Jincong Zhou
- & Qianwen Sun
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Article
| Open AccessA papain-like cysteine protease-released small signal peptide confers wheat resistance to wheat yellow mosaic virus
Soil-borne wheat yellow mosaic virus (WYMV) poses a serious threat to global wheat production. Here, the authors report that the nuclear inclusion protease-a produced by WYMV interacts with a small peptide catalyzed by TaRD21A protease activity to mediate WYMV resistance through activating MAPK signaling pathway.
- Peng Liu
- , Chaonan Shi
- & Jian Yang
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Article
| Open AccessThe rate of epigenetic drift scales with maximum lifespan across mammals
Epigenetic drift has been hypothesized to contribute to epigenetic clock signals and variation in lifespan across species. Here, the authors show that an empirical measure of epigenetic drift scales with maximum lifespan across four mammal species and accumulates in non-random genomic locations.
- Emily M. Bertucci-Richter
- & Benjamin B. Parrott
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Article
| Open AccessGene duplication and deletion caused by over-replication at a fork barrier
Gene duplications and deletions are important drivers of evolution and disease. Here, the authors show that excess DNA generated at a replication fork barrier can be integrated at a new genomic site causing both a gene duplication and a deletion.
- Judith Oehler
- , Carl A. Morrow
- & Matthew C. Whitby
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Article
| Open AccessEvaluation of circulating plasma proteins in breast cancer using Mendelian randomisation
Proteomics of blood samples is a promising avenue for cancer diagnosis. Here, the authors conduct Mendelian randomisation analysis of protein levels across multiple cohorts, and identify 5 proteins that show promise as biomarkers for the long-term risk of breast cancer, and as potential drug targets.
- Anders Mälarstig
- , Felix Grassmann
- & Åsa K. Hedman
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Article
| Open AccessGlobal pathogenomic analysis identifies known and candidate genetic antimicrobial resistance determinants in twelve species
A global analysis of antimicrobial resistance (AMR) across 27,155 genomes and 69 drugs reveals patterns in AMR gene transfer between species and identifies 142 AMR gene candidates, two of which were tested and confirmed as contributing to AMR.
- Jason C. Hyun
- , Jonathan M. Monk
- & Bernhard O. Palsson
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Article
| Open AccessACS-20/FATP4 mediates the anti-ageing effect of dietary restriction in C. elegans
Dietary restriction is one of the most effective ways to delay ageing. Here, the authors discover a highly conserved lipid metabolism gene functions through transcriptional regulation mechanisms to regulate proteostasis, lifespan and healthspan in response to low nutrients in C. elegans.
- Zi Wang
- , Lina Zou
- & Di Chen
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Article
| Open AccessIn vivo imaging of mitochondrial DNA mutations using an integrated nano Cas12a sensor
Mutations in mitochondrial DNA (mtDNA) play critical roles in human diseases. Here, the authors describe an integrated Cas12a sensor for sensing mtDNA mutations in vivo, showing potential for diagnostic and therapeutic purposes.
- Yanan Li
- , Yonghua Wu
- & Kaixiang Zhang
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Article
| Open AccessHigh-resolution temporal profiling of E. coli transcriptional response
Understanding how cells dynamically adapt to their environment is important, but temporal information about cellular behaviour is often limited. Here, Miano et al. apply unsupervised machine learning to a dataset describing the activity of over 1,800 promoters in E. coli, measured every 10 minutes, defining three primary stages of promoter activation in response to heavy metal stress.
- Arianna Miano
- , Kevin Rychel
- & Jeff Hasty
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Article
| Open AccessFear extinction is regulated by the activity of long noncoding RNAs at the synapse
Synaptic activity controls the extinction of conditioned fear. Here the authors discovered a new way that the brain controls memories of fear: a long noncoding RNA called Gas5 that coordinates the activity of RNA granules in the synaptic compartment.
- Wei-Siang Liau
- , Qiongyi Zhao
- & Timothy W. Bredy
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Article
| Open AccessLoss-of-function of an α-SNAP gene confers resistance to soybean cyst nematode
Here, the authors show that the soybean GmSNAP02 gene confers a unique mode of resistance to the soybean cyst nematode Heterodera glycines through loss-of-function mutations that implicate GmSNAP02 as a nematode virulence target.
- Mariola Usovsky
- , Vinavi A. Gamage
- & Andrew M. Scaboo
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Article
| Open AccessTargetable lesions and proteomes predict therapy sensitivity through disease evolution in pediatric acute lymphoblastic leukemia
The role of clonal evolution on the actionable proteome and response to therapy in childhood acute lymphoblastic leukemia (ALL) remains unknown. Here, targeted sequencing and proteomic analysis of paired ALL diagnosis and relapsed samples revealed PARP1 as a potential therapeutic target.
- Amanda C. Lorentzian
- , Jenna Rever
- & Philipp F. Lange
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Article
| Open AccessLHP1-mediated epigenetic buffering of subgenome diversity and defense responses confers genome plasticity and adaptability in allopolyploid wheat
The regulation of genetic diversity resulting from polyploidization and its impact on environmental adaptability remain unclear. Here, the authors show that LHP1-mediated epigenetic buffering of subgenome diversity and defense responses confers genome plasticity and adaptability in allopolyploid wheat.
- Zijuan Li
- , Yuyun Zhang
- & Yijing Zhang
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Article
| Open AccessCRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus
Culex mosquitoes are carriers of major diseases like West Nile virus and are a public health concern. Here the authors present a CRISPR-Cas9 gene drive as a control technology in the Culex quinquefasciatus mosquito species.
- Tim Harvey-Samuel
- , Xuechun Feng
- & Valentino M. Gantz
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Article
| Open AccessTranscriptome-wide association analyses reveal the impact of regulatory variants on rice panicle architecture and causal gene regulatory networks
Panicle architecture significantly determines rice grain yield. Here, the authors investigate the transcriptome of young panicles from 275 rice varieties and propose a method to identify causal genes for panicle traits and construct regulatory networks.
- Luchang Ming
- , Debao Fu
- & Weibo Xie
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Article
| Open AccessA toxin-antidote system contributes to interspecific reproductive isolation in rice
Orzya meridionalis is a wild rice species that has reproductive isolation with Asian cultivated rice. Here, the authors report the cloning of the second locus controlling hybrid male sterility between the two species and show the encoded toxin-antidote system provides stacked reproductive isolation for maintaining species identity.
- Shimin You
- , Zhigang Zhao
- & Jianmin Wan
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Article
| Open AccessNanoscale patterning of collagens in C. elegans apical extracellular matrix
The extracellular matrix (ECM) is critical for animal development and intricately patterned at multiple scales. Here Adams and Pooranachithra et al. show how specific collagens are precisely localized to struts, highly patterned sub-micron structures in the nematode cuticle ECM.
- Jennifer R. G. Adams
- , Murugesan Pooranachithra
- & Andrew D. Chisholm
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Article
| Open Accessc-di-GMP inhibits the DNA binding activity of H-NS in Salmonella
H-NS is a global regulatory protein that represses expression of many genes in bacteria. Here, Li et al. show that a second messenger, cyclic di-GMP, binds to H-NS and inhibits its binding to DNA, thus relieving H-NS-mediated transcriptional silencing.
- Shuyu Li
- , Qinmeng Liu
- & Lei Zhang
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Article
| Open AccessGenome-wide CRISPR off-target prediction and optimization using RNA-DNA interaction fingerprints
Analysis of CRISPR-Cas off-targets is important. Here the authors incorporate molecular dynamics simulations in the computational analysis of CRISPR editing and report the CRISOT tool suite and apply this to genome-wide CRISPR off-target prediction and sgRNA optimisation.
- Qinchang Chen
- , Guohui Chuai
- & Qi Liu
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Article
| Open AccessIntegrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture
Kidney stone disease is a complex disorder with high heritability and prevalence. Here, the authors perform a large genome-wide association study meta-analysis, identifying 28 new loci and genes potentially involved in disease etiology.
- Xingjie Hao
- , Zhonghe Shao
- & Chaolong Wang
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Article
| Open AccessAsymmetric CRISPR enabling cascade signal amplification for nucleic acid detection by competitive crRNA
New strategies are being developed to simplify CRISPR-based nucleic acid detection. By investigating the competitive reaction between a full-sized crRNA and split crRNA for CRISPR-Cas12a, the authors develop an asymmetric CRISPR assay for amplification-free, cascade signal amplification detection of nucleic acids.
- Jeong Moon
- & Changchun Liu
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Article
| Open AccessThe homeodomain transcriptional regulator DVE-1 directs a program for synapse elimination during circuit remodeling
Synapse elimination is a critical process in the maturation of brain circuitry. Here the authors identify a key transcriptional program in Caenorhabditis elegans that directs the elimination of juvenile synapses during developmental circuit rewiring.
- Kellianne D. Alexander
- , Shankar Ramachandran
- & Michael M. Francis
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Article
| Open AccessTransposable element-initiated enhancer-like elements generate the subgenome-biased spike specificity of polyploid wheat
The direct impacts of transposable element dynamics on polyploid regulation and developmental specificity remain unclear. Here, the authors show that a large proportion of enhancer-like elements (ELEs) are mainly originated from RLG_famc7.3 specifically expanded in subgenome A, producing active nascent transcripts and influencing wheat spike development.
- Yilin Xie
- , Songbei Ying
- & Yijing Zhang
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Perspective
| Open AccessMulti-omics for studying and understanding polar life
Endangered polar ecosystems play critical roles in the Earth’s climate system and comprise many different habitats with unique organisms. Here, the authors propose a community road map to use multi-omics data from polar organisms for conservation, ecosystem services and societal gain.
- M. S. Clark
- , J. I. Hoffman
- & T. Mock
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Article
| Open AccessMutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
Vein of Galen malformations (VOGMs) are severe congenital brain arteriovenous malformations. Here the authors work to elucidate the pathogenesis of VOGMs by performing an integrated analysis of 310 VOGM proband family exomes and 336,326 human cerebrovasculature single-cell transcriptomes to identify mutations of key signaling regulators.
- Shujuan Zhao
- , Kedous Y. Mekbib
- & Kristopher T. Kahle
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Article
| Open AccessThe metabolic, virulence and antimicrobial resistance profiles of colonising Streptococcus pneumoniae shift after PCV13 introduction in urban Malawi
Pneumococcal vaccination has been shown to promote emergence of non-vaccine S. pneumoniae serotypes. Here, the authors use data from Malawi to investigate whether vaccine introduction also results in changes in metabolic, virulence, and antimicrobial resistance profiles of circulating strains.
- Uri Obolski
- , Todd D. Swarthout
- & Robert S. Heyderman
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Article
| Open AccessJoint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape
The genetic architecture of normal-range cranial vault shape in humans is poorly understood. Here, the authors extract cranial vault shape from MRI and conduct a multi-ancestry GWAS, identifying 30 independently associated genomic loci of which 29 are novel.
- Seppe Goovaerts
- , Hanne Hoskens
- & Peter Claes
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Article
| Open AccessPan-genome analysis of 13 Malus accessions reveals structural and sequence variations associated with fruit traits
A pan-genome can reduce bias in genetic diversity analysis inherent in using a single reference genome. Here, the authors assemble genomes of 10 diverse apple accessions, conduct pan-genome analysis together with three existing genomes, and reveal the role of mitogen-activated protein kinase homolog MMK2 in fruit coloration.
- Ting Wang
- , Shiyao Duan
- & Ting Wu
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Article
| Open AccessPolyethyleneimine-coated MXene quantum dots improve cotton tolerance to Verticillium dahliae by maintaining ROS homeostasis
Verticillum wilt is an important cotton disease caused by fungal pathogen Verticillium dahiae. Here, the authors assemble the genomes of defoliating and non-defoliating isolates of the pathogen, identify virulence gene SP3, and develop a disease control strategy using polyethyleneimine-coated MXene quantum dots.
- Ping Qiu
- , Jiayue Li
- & Longfu Zhu
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Article
| Open AccessDeep learning of human polyadenylation sites at nucleotide resolution reveals molecular determinants of site usage and relevance in disease
The authors develop deep learning models to identify genome-wide polyA sites at nucleotide resolution and calculate site strength. They further examine genomic parameters regulating site usage and reveal genetic variants altering polyA activity.
- Emily Kunce Stroup
- & Zhe Ji
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Article
| Open AccessHofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes
Placental inflammation is sometimes associated with health outcomes later in life. Here, the authors find that expression of genes associated with the homeostatic function of Hofbauer cells, a placenta-specific macrophage, are associated with protection from adult cardiovascular and depressive disorders
- Eamon Fitzgerald
- , Mojun Shen
- & Michael J. Meaney
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Article
| Open AccessSingle amino acid change alters specificity of the multi-allelic wheat stem rust resistance locus SR9
Among all wheat rust resistance genes, SR9 has the largest number of alleles. Here, the authors use gene cloning, complementation and comparative genetics to resolve the relationship among Sr9 alleles, confirm their allelic identities, and show that a single amino acid change leads to resistance to Ug99.
- Jianping Zhang
- , Jayaveeramuthu Nirmala
- & Evans Lagudah
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Article
| Open AccessBacteria can maintain rRNA operons solely on plasmids for hundreds of millions of years
Bacteria usually have at least one rRNA operon on the chromosome, suggesting that the exclusive presence of rRNA operons on a plasmid is rare and unlikely to be stably maintained. Here, Anda et al. find that at least four bacterial clades in different phyla lost their chromosomal rRNA operons independently, and one of the clades has maintained this peculiar genome organization for hundreds of millions of years.
- Mizue Anda
- , Shun Yamanouchi
- & Wataru Iwasaki
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Article
| Open AccessCopy number variation of the restorer Rf4 underlies human selection of three-line hybrid rice breeding
Ctyoplasmic male sterility gene WA352 and its fertility restorer Rf4 are widely used for commercial three-line hybrid rice production. Here, the authors investigate the origin, evolution, and variation of Rf4, and show that copy number variation of Rf4 contributes of fertility restoration in a dosage-dependent manner.
- Zhe Zhao
- , Zhi Ding
- & Letian Chen
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Article
| Open AccessA large meta-analysis identifies genes associated with anterior uveitis
Anterior Uveitis is a common inflammatory eye disease that can result in vision loss. Here, the authors perform GWAS and whole-exome analyses of Anterior Uveitis to identify the underlying genetics of HLA-B*27 positive and negative forms of the disease.
- Sahar Gelfman
- , Arden Moscati
- & Giovanni Coppola
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