Associations of genome-wide structural variations with phenotypic differences in cross-bred Eurasian pigs

Background During approximately 10,000 years of domestication and selection,a large number of structural variations(SVs)have emerged in the genome of pig breeds,profoundly influencing their phenotypes and the ability to adapt to the local environment.SVs(≥50 bp)are widely distributed in the genome,mainly in the form of insertion(INS),mobile element insertion(MEI),deletion(DEL),duplication(DUP),inversion(INV),and translocation(TRA).While studies have investigated the SVs in pig genomes,genome-wide association studies(GWAS)-based on SVs have been rarely conducted.Results Here,we obtained a high-quality SV map containing 123,151 SVs from 15 Large White and 15 Min pigs through integrating the power of several SV tools,with 53.95%of the SVs being reported for the first time.These high-quality SVs were used to recover the population genetic structure,confirming the accuracy of genotyping.Potential functional SV loci were then identified based on positional effects and breed stratification.Finally,GWAS were performed for 36 traits by genotyping the screened potential causal loci in the F2 population according to their corresponding genomic positions.We identified a large number of loci involved in 8 carcass traits and 6 skeletal traits on chromosome 7,with FKBP5 containing the most significant SV locus for almost all traits.In addition,we found several significant loci in intramuscular fat,abdominal circumference,heart weight,and liver weight,etc.Conclusions We constructed a high-quality SV map using high-coverage sequencing data and then analyzed them by performing GWAS for 25 carcass traits,7 skeletal traits,and 4 meat quality traits to determine that SVs may affect body size between European and Chinese pig breeds.

The occurrence,inheritance,and segregation of complex genomic structural variation in synthetic Brassica napus

"Synthetic"allopolyploids recreated by interspecific hybridization play an important role in providing novel genomic variation for crop improvement.Such synthetic allopolyploids often undergo rapid genomic structural variation(SV).However,how such SV arises,is inherited and fixed,and how it affects important traits,has rarely been comprehensively and quantitively studied in advanced generation synthetic lines.A better understanding of these processes will aid breeders in knowing how to best utilize synthetic allopolyploids in breeding programs.Here,we analyzed three genetic mapping populations(735 DH lines)derived from crosses between advanced synthetic and conventional Brassica napus(rapeseed)lines,using whole-genome sequencing to determine genome composition.We observed high tolerance of large structural variants,particularly toward the telomeres,and preferential selection for balanced homoeologous exchanges(duplication/deletion events between the A and C genomes resulting in retention of gene/chromosome dosage between homoeologous chromosome pairs),including stable events involving whole chromosomes("pseudoeuploidy").Given the experimental design(all three populations shared a common parent),we were able to observe that parental SV was regularly inherited,showed genetic hitchhiking effects on segregation,and was one of the major factors inducing adjacent novel and larger SV.Surprisingly,novel SV occurred at low frequencies with no significant impacts on observed fertility and yield-related traits in the advanced generation synthetic lines.However,incorporating genome-wide SV in linkage mapping explained significantly more genetic variance for traits.Our results provide a framework for detecting and understanding the occurrence and inheritance of genomic SV in breeding programs,and support the use of synthetic parents as an important source of novel trait variation.

Structural variation(SV)-based pan-genome and GWAS reveal the impacts of SVs on the speciation and diversification of allotetraploid cottons

Structural variations(SVs)have long been described as being involved in the origin,adaption,and domes-tication of species.However,the underlying genetic and genomic mechanisms are poorly understood.Here,we report a high-quality genome assembly of Gossypium barbadense acc.Tanguis,a landrace that is closely related to formation of extra-long-staple(ELS)cultivated cotton.An SV-based pan-genome(Pan-SV)was then constructed using a total of 182593 non-redundant SVs,including 2236 inversions,97398 insertions,and 82959 deletions from 11 assembled genomes of allopolyploid cotton.The utility of this Pan-sV was then demonstrated through population structure analysis and genome-wide association studies(GWASs).Using segregation mapping populations produced through crossing ELS cotton and the landrace along with an Sv-based GWAs,certain SVs responsible for speciation,domestication,and improvement in tetraploid cottons were identified.Importantly,some of the SVs presently identified as associated with the yield and fiber quality improvement had not been identified in previous SNP-based GWAS.In particular,a 9-bp insertion or deletion was found to associate with elimination of the interspecific reproductive isolation between Gossypium hirsutum and G.barbadense.Collectively,this study provides new insights into genome-wide,gene-scale SVs linked to important agronomic traits in a major crop spe-cies and highlights the importance of sVs during the speciation,domestication,and improvement of culti-vated crop species.

Integrative Identification by Hi‑C Revealed Distinct Advanced Structural Variations in Lung Adenocarcinoma Tissue

Advanced three-dimensional structure variations of chromatin in large genome fragments,such as conversion of A/B compartment,topologically associated domains(TADs)and chromatin loops are related closely to occurrence of malignant tumors.However,the structural characteristics of lung cancer still remain uncovered.In this study,we used high-throughput chromosome(Hi-C)conformation capture technology to detect the advanced structural variations in chromatin of two nonsmoking lung adenocarcinoma(LUAD)tumor and paired normal tissues.The results indicate that significant chromatin variations are detected in tumor tissues compared with normal tissues.At compartment scale,the main conversion type of compartment is A→B in tumor tissues,which are concentrated mainly on chromosome 3(Chr3)(33.6%).A total of 216 tumor-specific TADs are identified in tumor tissues,which are distributed mainly in Chr1(19),Chr2(15)and Chr3(17).Forty-one distinct enhancer-promoter loops are observed in tumor tissue,which are associated closely to tumor-related pathways including mitogen-activated protein kinase(MAPK),Phosphatidylinositol-3-kinase-Protein kinase B(PI3K-AKT),Ras,Wnt and Ras1.The most important observation in this study is that we identify five important genes(SYT16,NCEH1,NXPE3,MB21D2,and DZIP1L),which are detected in both A→B compartment,TADs and chromatin loops in tumor samples,and four of these genes(NCEH1,NXPE3,MB21D2,and DZIP1L)locate on q arm of Chr3.Further gene expression and invasion experiment analysis show that NCEH1,MB21D2 and SYT16 are involved in the tumor development.Thus,we provide a comprehensive overview of advanced structures in LUAD for the first time and provide a basis for further research on the genetic variation of this tumor.

Directed yeast genome evolution by controlled introduction of trans-chromosomic structural variations

Naturally occurring structural variations(SVs)are a considerable source of genomic variation that can reshape the 3D architecture of chromosomes.Controllable methods aimed at introducing the complex SVs and their related molecular mechanisms have remained farfetched.In this study,an SV-prone yeast strain was developed using Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution(SCRaMbLE)technology with two synthetic chromosomes,namely synV and synX.The biosynthesis of astaxanthin is used as a readout and a proof of concept for the application of SVs in industries.Our findings showed that complex SVs,including a pericentric inversion and a trans-chromosome translocation between synV and synX,resulted in two neo-chromosomes and a 2.7-fold yield of astaxanthin.Also,genetic targets were mapped,which resulted in a higher astaxanthin yield,thus demonstrating the SVs’ability to reorganize genetic information along the chromosomes.The rational design of trans-chromosome translocation and pericentric inversion enabled precise induction of these phenomena.Collectively,this study provides an effective tool to not only accelerate the directed genome evolution but also to reveal the mechanistic insight of complex SVs for altering phenotypes.

A review of the pangenome:how it affects our understanding of genomic variation,selection and breeding in domestic animals?

As large-scale genomic studies have progressed,it has been revealed that a single reference genome pattern cannot represent genetic diversity at the species level.While domestic animals tend to have complex routes of origin and migration,suggesting a possible omission of some population-specific sequences in the current reference genome.Conversely,the pangenome is a collection of all DNA sequences of a species that contains sequences shared by all individuals(core genome)and is also able to display sequence information unique to each individual(variable genome).The progress of pangenome research in humans,plants and domestic animals has proved that the missing genetic components and the identification of large structural variants(SVs)can be explored through pangenomic studies.Many individual specific sequences have been shown to be related to biological adaptability,phenotype and important economic traits.The maturity of technologies and methods such as third-generation sequencing,Tel-omere-to-telomere genomes,graphic genomes,and reference-free assembly will further promote the development of pangenome.In the future,pangenome combined with long-read data and multi-omics will help to resolve large SVs and their relationship with the main economic traits of interest in domesticated animals,providing better insights into animal domestication,evolution and breeding.In this review,we mainly discuss how pangenome analysis reveals genetic variations in domestic animals(sheep,cattle,pigs,chickens)and their impacts on phenotypes and how this can contribute to the understanding of species diversity.Additionally,we also go through potential issues and the future perspectives of pangenome research in livestock and poultry.

Genomic structural variation in tomato and its role in plant immunity

It is well known that large genomic variations can greatly impact the phenotype of an organism.Structural Variants(SVs)encompass any genomic variation larger than 30 base pairs,and include changes caused by deletions,inversions,duplications,transversions,and other genome modifications.Due to their size and complex nature,until recently,it has been difficult to truly capture these variations.Recent advances in sequencing technology and computational analyses now permit more extensive studies of SVs in plant genomes.In tomato,advances in sequencing technology have allowed researchers to sequence hundreds of genomes from tomatoes,and tomato relatives.These studies have identified SVs related to fruit size and flavor,as well as plant disease response,resistance/susceptibility,and the ability of plants to detect pathogens(immunity).In this review,we discuss the implications for genomic structural variation in plants with a focus on its role in tomato immunity.We also discuss how advances in sequencing technology have led to new discoveries of SVs in more complex genomes,the current evidence for the role of SVs in biotic and abiotic stress responses,and the outlook for genetic modification of SVs to advance plant breeding objectives.

Potential influential topics in information science based on citation structural variation approach

This study aims to identify potential influential literature and potential influential topics in the field of information science(IS).Using citation structural variation approach,provided by CiteSpace,we discerned the potential influential theses in IS.Then,we proposed an analyzing framework based on"citation network-citation structural variation-citation cluster,"which is used to discern the potential influential topics in IS.Using the structural variation approach,we analyzed the contents and features of potential influential theses.The potential influential topics,discerned by the"citation network-citation structural variation-citation cluster"framework,corroborated the existing knowledge base to some extent and seemed to be divergent and intermingled.Such potential impact literature and potential impact research topics are of certain reference value for future frontier research.

A telomere-to-telomere genome assembly of Zhonghuang 13,a widely-grown soybean variety from the original center of Glycine max

Soybean(Glycine max)stands as a globally significant agricultural crop,and the comprehensive assembly of its genome is of paramount importance for unraveling its biological characteristics and evolutionary history.Nevertheless,previous soybean genome assemblies have harbored gaps and incompleteness,which have constrained in-depth investigations into soybean.Here,we present Telomere-to-Telomere(T2T)assembly of the Chinese soybean cultivar Zhonghuang 13(ZH13)genome,termed ZH13-T2T,utilizing PacBio Hifi and ONT ultralong reads.We employed a multi-assembler approach,integrating Hifiasm,NextDenovo,and Canu,to minimize biases and enhance assembly accuracy.The assembly spans 1,015,024,879 bp,effectively resolving all 393 gaps that previously plagued the reference genome.Our annotation efforts identified 50,564 high-confidence protein-coding genes,707 of which are novel.ZH13-T2T revealed longer chromosomes,421 not-aligned regions(NARs),112 structure variations(SVs),and a substantial expansion of repetitive element compared to earlier assemblies.Specifically,we identified 25.67 Mb of tandem repeats,an enrichment of 5S and 48S rDNAs,and characterized their genotypic diversity.In summary,we deliver the first complete Chinese soybean cultivar T2T genome.The comprehensive annotation,along with precise centromere and telomere characterization,as well as insights into structural variations,further enhance our understanding of soybean genetics and evolution.

SYNTHESIS OF MACROPOROUS POLYACRYLAMIDE AND POLY(NISOPROPYLACRYLAMIDE) MONOLITHS VIA FRONTAL POLYMERIZATION AND INVESTIGATION OF PORE STRUCTURE VARIATION OF MONOLITHS

A novelty method,frontal polymerization(FP),was employed to directly produce a series of polyacrylamide (PAM),poly(N-isopropylacrylamide)(PNIPAM) and acrylamide-N-isopropylacrylamide copolymer macroporous monoliths. Field emission scanning electronic microscope and mercury intrusion method were adopted to measure some parameters of these monoliths,such as frame,pore size distribution as well as porosity.Effects of types of monomer,thicker and surfactant on porous structure of monoliths were studied.A var...

Genome assembly of KA105,a new resource for maize molecular breeding and genomic research

Superior inbred lines are central to maize breeding as sources of natural variation.Although many elite lines have been sequenced,less sequencing attention has been paid to newly developed lines.We constructed a genome assembly of the elite inbred line KA105,which has recently been developed by an arti-ficial breeding population named Shaan A and has shown desirable characteristics for breeding.Its pedigree showed genetic divergence from B73 and other lines in its pedigree.Comparison with the B73 reference genome revealed extensive structural variation,58 presence/absence variation(PAV)genes,and 1023 expanded gene families,some of which may be associated with disease resistance.A network-based integrative analysis of stress-induced transcriptomes identified 13 KA105-specific PAV genes,of which eight were induced by at least one kind of stress,participating in gene modules responding to stress such as drought and southern leaf blight disease.More than 200,000 gene pairs were differentially correlated between KA105 and B73 during kernel development.The KA105 reference genome and transcriptome atlas are a resource for further germplasm improvement and surveys of maize genomic variation and gene function.

Characterizing structural variants based on graph-genotyping provides insights into pig domestication and local adaption

Structural variants(SVs),such as deletions(DELs)and insertions(INSs),contribute substantially to pig genetic diversity and phenotypic variation.Using a library of SVs discovered from long-read primary assemblies and short-read sequenced genomes,we map pig genomic SVs with a graph-based method for re-genotyping SVs in 402 genomes.Our results demonstrate that those SVs harboring specific trait-associated genes may greatly shape pig domestication and local adaptation.Further characterization of SVs reveals that some population-stratified SVs may alter the transcription of genes by affecting regulatory elements.We identify that the genotypes of two DELs(296-bp DEL,chr7:52,172,101e52,172,397;278-bp DEL,chr18:23,840,143 e23,840,421)located in muscle-specific enhancers are associated with the expression of target genes related to meat quality(FSD2)and muscle fiber hypertrophy(LMOD2 and WASL)in pigs.Our results highlight the role of SVs in domestic porcine evolution,and the identified candidate functional genes and SVs are valuable resources for future genomic research and breeding programs in pigs.

我国公立医院财政拨款收入的结构变动特征分析

目的 分析公立医院财政拨款收入的结构变动特征。方法 基于2011—2020年将考察时间段调整为2010—2019年《中国卫生健康统计年鉴》的数据,应用结构变动度分析方法。结果 2010—2019年,全国公立医院的财政拨款收入规模呈现逐年上升的趋势。我国不同级别公立医院的财政拨款结构变动贡献率从大到小依次为三级医院(58.43%)、二级医院(39.26%)、基层医疗卫生机构(2.31%)。各类公立医院的贡献率从大到小依次为精神病医院(40.25%)、综合医院(17.13%)、传染病医院(14.64%)、中医(民族)医院(7.85%)、儿童医院(6.00%)、妇产医院/妇幼保健院(5.35%)、其他专科医院(4.90%)、职业病防治院(3.88%)。结论 需要政府落实职责,在财政拨款安排中重视各类型、各级别公立医院的合理平衡,科学规划财政投入标准及支持力度,进一步推动分级诊疗制度,保证不同类型、级别医院的平稳运行。

Two new SINE insertion polymorphisms in pig Vertnin(VRTN)gene revealed by comparative genomic alignment

Despite one SINE retrotransposon insertion polymorphism(sRTIP)in the vertebrae development-associated(VRTN)gene was identified in pigs,the structural variations(SVs)in VRTN gene and its proximal flank regions were largely unknown.VRTN genic and flanking sequences from 14 breeds were assembled or downloaded from whole genome shotgun contings(WGS)database,and aligned to identify the SVs with Clustalx,and retrotransposons in VRTN gene were annotated by RepeatMasker,the splicing patterns of VRTN gene were predicted by Genescan,and large SVs were evaluated by PCR.A total of 12 small SVs and three large SVs in intron of VRTN,derived from SINE insertion polymorphisms.were identifed,and two of them(VRTN-sRTIP2 and VRTN-sRTIP3)were not reported before.These VRTN-sRTIPs may affect the splicing patterns of VRTN.They displayed polymorphisms in most detected eight breeds.VRTN-sRTIP2 and VRTN-sRTIP3 showed Hardy-Weinberg equilibrium distributions in most populations except the Chinese local Erhualian pigs,while VRTN-sRTIP1 showed genetic equilbrium in Erhualian pigs.Three VRTN-sRTIPs were identified,and displayed polymorphisms in pigs,and two of them were not reported before.These SVs provide a useful molecular markers for genetic analysis in pigs,and offer new information to facilitate the understanding the SVs of VRTN gene and their putative roles in the variation of vertebral number.

Plastome characteristics and species identification of Chinese medicinal wintergreens(Gaultheria,Ericaceae)

Wintergreen oil is a folk medicine widely used in foods,pesticides,cosmetics and drugs.In China,nine out of 47 species within Gaultheria(Ericaceae)are traditionally used as Chinese medicinal wintergreens;however,phylogenetic approaches currently used to discriminating these species remain unsatisfactory.In this study,we sequenced and characterized plastomes from nine Chinese wintergreen species and identified candidate DNA barcoding regions for Gaultheria.Each Gaultheria plastome contained 110 unique genes(76 protein-coding,30 tRNA,and four rRNA genes).Duplication of trnfM,rps14,and rpl23 genes were detected,while all plastomes lacked ycf1 and ycf2 genes.Gaultheria plastomes shared substantially contracted SSC regions that contained only the ndhF gene.Moreover,plastomes of Gaultheria leucocarpa var.yunnanensis contained an inversion in the LSC region and an IR expansion to cover the ndhF gene.Multiple rearrangement events apparently occurred between the Gaultheria plastomes and those from several previously reported families in Ericales.Our phylogenetic reconstruction using 42 plastomes revealed well-supported relationships within all nine Gaultheria species.Additionally,seven mutational hotspot regions were identified as potential DNA barcodes for Chinese medicinal wintergreens.Our study is the first to generate complete plastomes and describe the structural variations of the complicated genus Gaultheria.In addition,our findings provide important resources for identification of Chinese medicinal wintergreens.

Unraveling the puzzle of the origin and evolution of cotton A-genome

Gossypium hirsutum,the most widely planted cotton species,its evolution has long been an unsolved puzzle because of its hybrid origin from D-genome and A-genome species.To better understand the genetic component of cotton,Huang et al.recently sequenced and assembled the first A1-genome G.herbaceum,and updated the A2-genome G.arboreum and(AD)1-genome G.hirsutum.On the basis of the three reference genomes,they resolved existing controversial concepts and provided novel evolutionary insights surrounding the A-genome.

Solutions for a class of Hamiltonian systems on time scales with non-local boundary conditions

In this work,the solvability of a class of second-order Hamiltonian systems on time scales is generalized to non-local boundary conditions.The measurements obtained by non-local conditions are more accurate than those given by local conditions in some problems.Compared with the known results,this work establishes the variational structure in an appropriate Sobolev’s space.Then,by applying the mountain pass theorem and symmetric mountain pass theorem,the existence and multiplicity of the solutions are obtained.Finally,some examples with numerical simulation results are given to illustrate the correctness of the results obtained.

Robust Benchmark Structural Variant Calls of An Asian Using State-of-the-art Long-read Sequencing Technologies

The importance of structural variants(SVs)for human phenotypes and diseases is now recognized.Although a variety of SV detection platforms and strategies that vary in sensitivity and specificity have been developed,few benchmarking procedures are available to confidently assess their performances in biological and clinical research.To facilitate the validation and application of these SV detection approaches,we established an Asian reference material by characterizing the genome of an Epstein-Barr virus(EBV)-immortalized B lymphocyte line along with identified benchmark regions and high-confidence SV calls.We established a high-confidence SV callset with 8938 SVs by integrating four alignment-based SV callers,including 109×Pacific Bio sciences(PacBio)continuous long reads(CLRs),22×PacBio circular consensus sequencing(CCS)reads,104×Oxford Nanopore Technologies(ONT)long reads,and 114×Bionano optical mapping platform,and one de novo assembly-based SV caller using CCS reads.A total of 544 randomly selected SVs were validated by PCR amplification and Sanger sequencing,demonstrating the robustness of our SV calls.Combining trio-binning-based haplotype assemblies,we established an SV benchmark for identifying false negatives and false positives by constructing the continuous high-confidence regions(CHCRs),which covered 1.46 gigabase pairs(Gb)and 6882 SVs supported by at least one diploid haplotype assembly.Establishing high-confidence SV calls for a benchmark sample that has been characterized by multiple technologies provides a valuable resource for investigating SVs in human biology,disease,and clinical research.

Research Progress of Genomic Variation in Psoriasis

As a typical representative of global complex diseases,psoriasis has attracted widespread attention because of its high heritability,heterogeneity,and incidence.Environmentally induced activation of the inflammatory-immune axis in patients with psoriasis relies on genetic regulation of genomic variation.The heritability of psoriasis exceeds 80%,and research of genomic variation in psoriasis is of great significance to the interpretation of the biological pathogenesis of the disease.The development of genome-wide association studies(GWASs)has provided a powerful means for the capture of psoriasis susceptibility genes.More than 100 psoriasis susceptibility loci have been captured,enabling humans to gain a breakthrough understanding of the genetics and traits of psoriasis.With the advancement of research methods,increasingly more genetic methodologies are being used to capture the locations and types of variants outside the scope of GWAS scanning,making up for the inclinations and deficiencies of traditional GWAS capture of gene loci in a more detailed manner.This review covers several decades of research on genomic variation in psoriasis,including GWASs in psoriasis,the capture of functional gene variant types,and the translation of genomic variation into precision medicine;summarizes the research progress of genomic variation in psoriasis;and provides a theoretical reference for future genetic-based research of the mechanisms underlying psoriasis.

STUDY ON THE AMPLITUDE AND PHASE VARIATION OF EQUATORIAL WARMING BY USING COMPLEX EOF(CEOF) ANALYSIS

In order to understand the mechanism of equatorial warming during El Nio and to search for its prediction methods, the complex EOF analysis is used in this article to study the time-space structure of SST variation in the tropical Pacific