Local cattle breeds play a critical role in breeding programs due to their genetic adaptations to diverse environmental conditions.However,the genomic architecture of local cattle breeds in Kazakhstan remains largely ...Local cattle breeds play a critical role in breeding programs due to their genetic adaptations to diverse environmental conditions.However,the genomic architecture of local cattle breeds in Kazakhstan remains largely unexplored.This study utilized whole-genome sequencing data from Kazakh cattle to elucidate their genetic composition,uncovering three primary ancestral components:European,Eurasian,and East Asian taurine.The East Asian taurine lineage likely represents the earliest genetic contribution to Kazakh cattle but was largely replaced by subsequent waves of cattle migrations across Eurasia,leaving only a minor genetic signature in the current cattle population.In contrast,Eurasian taurine ancestry predominated in the Alatau and Kazakh local breeds,while the European taurine component was most prevalent in Kazakh white-headed cattle,consistent with their documented breeding history.Kazakh cattle exhibited higher genetic diversity and lower inbreeding coefficients compared to European commercial breeds,reflecting reduced exposure to intense artificial selection.A strong selection signal was identified on chromosome 6 at a locus encompassing PDGFRA,KIT,and KDR,which may be associated with the white-headed pigmentation characteristic of Kazakh white-headed cattle.Additional genes under selection were linked to lipid metabolism(IRS1,PRKG1,and ADCY8),meat production traits(KCNMA1,PDGFRA,HIF1A,and ANTXR1),and dairy production(ATP2B1,DHX15,FUK,NEGR1,CCDC91,COG4,and PTK2B).This study represents the first comprehensive analysis of nuclear genome data from local Kazakh cattle.It highlights the impact of historical cattle migrations across Eurasia on their genetic landscape and identifies key genomic regions under selection.These findings advance our understanding of the evolutionary history of cattle and offer valuable genetic resources for future breeding strategies.展开更多
Oil and protein content and fatty acid composition are quality traits in peanut.Elucidating the genetic mechanisms underlying these traits may help researchers to obtain improved cultivars by molecular breeding.Whole-...Oil and protein content and fatty acid composition are quality traits in peanut.Elucidating the genetic mechanisms underlying these traits may help researchers to obtain improved cultivars by molecular breeding.Whole-genome resequencing of a recombinant inbred population of 318 lines was performed to construct a high-density linkage map and identify QTL for peanut quality.The map,containing 4561 bin markers,covered 2032 c M with a mean marker density of 0.45 c M.A total of 110 QTL for oil and protein content,and fatty acid composition were mapped on the 18 peanut chromosomes.The QTL q A05.1 was detected in four environments and showed a major phenotypic effect on the contents of oil,protein,and six fatty acids.The genomic region spanned by q A05.1,corresponding to a physical interval of approximately 1.5 Mb,contains two SNPs polymorphic between the parents that could cause missense mutations.The two SNP sites were employed as KASP markers and validated using lines with extremely high and low oil contents.These sites may be useful in the marker-assisted breeding of peanut cultivars with high oil contents.展开更多
Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive.We implemented whole-genome sequencing(WGS) analysis of 8 families with monozygotic(MZ) twin pairs discordant ...Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive.We implemented whole-genome sequencing(WGS) analysis of 8 families with monozygotic(MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations(DNMs) or inherited variants with susceptibility to schizophrenia. Eight non-synonymous DNMs(including one splicing site) were identified and shared by twins, which were either located in previously reported schizophrenia risk genes(p.V24689 I mutation in TTN, p.S2506 T mutation in GCN1L1, IVS3+1G > T in DOCK1) or had a benign to damaging effect according to in silico prediction analysis. By searching the inherited rare damaging or loss-of-function(LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes, we were able to distill genetic alterations in several schizophrenia risk genes, including GAD1, PLXNA2, RELN and FEZ1. Four inherited copy number variations(CNVs; including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families, respectively. Most of families carried both missense DNMs and inherited risk variants, which might suggest that DNMs, inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility. Our results support that schizophrenia is caused by a combination of multiple genetic factors, with each DNM/variant showing a relatively small effect size.展开更多
The phenotypic diversity resulting from artificial or natural selection of sheep has made a significant contribution to human civilization.Hu sheep are a local sheep breed unique to China with high reproductive rates ...The phenotypic diversity resulting from artificial or natural selection of sheep has made a significant contribution to human civilization.Hu sheep are a local sheep breed unique to China with high reproductive rates and rapid growth.Genomic selection signatures have been widely used to investigate the genetic mechanisms underlying phenotypic variation in livestock.Here,we conduct whole-genome sequencing of 207 Hu sheep and compare them with the wild ancestors of domestic sheep(Asiatic mouflon)to investigate the genetic characteristics and selection signatures of Hu sheep.Based on six signatures of selection approaches,we detect genomic regions containing genes related to reproduction(BMPR1B,BMP2,PGFS,CYP19,CAMK4,GGT5,and GNAQ),vision(ALDH1A2,SAG,and PDE6B),nervous system(NAV1),and immune response(GPR35,SH2B2,PIK3R3,and HRAS).Association analysis with a population of 1299 Hu sheep reveals that those missense mutations in the GPR35(GPR35 g.952651 A>G;GPR35 g.952496 C>T)and NAV1(NAV1 g.84216190 C>T;NAV1 g.84227412 G>A)genes are significantly associated(P<0.05)with immune and growth traits in Hu sheep,respectively.This research offers unique insights into the selection characteristics of Hu sheep and facilitates further genetic improvement and molecular investigations.展开更多
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity.In this study,we identified all classes of genomic variants from whole-genome sequencing (WGS) datas...Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity.In this study,we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD,including de novo mutations,inherited variants,copy number variants (CNVs) and genomic structural variants.A higher mutation rate (Poisson test,P<2.2×10^(-16)) in exonic (1.37×10^(-8)) and 3'-UTR regions (1.42×10^(-8)) was revealed in comparison with that of whole genome (1.05×10^(-8)).Using an integrated model,we identified 87 potentially risk genes (P<0.01) from 4832 genes harboring various rare deleterious variants,including CHD8 and NRXN2,implying that the disorders may be in favor to multiple-hit.In particular,frequent rare inherited mutations of several microcephaly-associated genes (ASPM,WDR62,and ZNF335)were found in ASD.In chromosomal structure analyses,we found four de novo CNVs and one de novo chromosomal rearrangement event,including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1,which causes Angelman syndrome and microcephaly,and a disrupted TNR due to de novo chromosomal translocation t (1;5) (q25.1;q33.2).Taken together,our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD.Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders,such as ASD,could provide novel insights into pathogenesis,diagnosis and treatment.展开更多
Largemouth bass(Micropterus salmoides) is an economically important fish species in North America, Europe, and China. Various genetic improvement programs and domestication processes have modified its genome sequence ...Largemouth bass(Micropterus salmoides) is an economically important fish species in North America, Europe, and China. Various genetic improvement programs and domestication processes have modified its genome sequence through selective pressure, leaving nucleotide signals that can be detected at the genomic level. In this study,we sequenced 149 largemouth bass fish, including protospecies(imported from the US) and improved breeds(four domestic breeding populations from China). We detected genomic regions harboring certain genes associated with improved traits, which may be useful molecular markers for practical domestication, breeding, and selection. Subsequent analyses of genetic diversity and population structure revealed that the improved breeds have undergone more rigorous genetic changes. Through selective signal analysis, we identified hundreds of putative selective sweep regions in each largemouth bass line. Interestingly, we predicted 103 putative candidate genes potentially subjected to selection,including several associated with growth(psst1 and grb10), early development(klf9, sp4, and sp8), and immune traits(pkn2, sept2, bcl6, and ripk2). These candidate genes represent potential genomic landmarks that could be used to improve important traits of biological and commercial interest. In summary, this study provides a genome-wide map of genetic variations and selection footprints in largemouth bass, which may benefit genetic studies and accelerate genetic improvement of this economically important fish.展开更多
The abundance of domesticated sheep varieties and phenotypes is largely the result of long-term natural and artificial selection. However, there is limited information regarding the genetic mechanisms underlying pheno...The abundance of domesticated sheep varieties and phenotypes is largely the result of long-term natural and artificial selection. However, there is limited information regarding the genetic mechanisms underlying phenotypic variation induced by the domestication and improvement of sheep. In this study, to explore genomic diversity and selective regions at the genome level, we sequenced the genomes of 100 sheep across 10 breeds and combined these results with publicly available genomic data from 225 individuals, including improved breeds, Chinese indigenous breeds,African indigenous breeds, and their Asian mouflon ancestor. Based on population structure, the domesticated sheep formed a monophyletic group,while the Chinese indigenous sheep showed a clear geographical distribution trend. Comparative genomic analysis of domestication identified several selective signatures, including IFI44 and IFI44L genes and PANK2 and RNF24 genes, associated with immune response and visual function.Population genomic analysis of improvement demonstrated that candidate genes of selected regions were mainly associated with pigmentation,energy metabolism, and growth development.Furthermore, the IFI44 and IFI44L genes showed a common selection signature in the genomes of 30domesticated sheep breeds. The IFI44 c. 54413058C>G mutation was selected for genotyping and population genetic validation. Results showed that the IFI44 polymorphism was significantly associated with partial immune traits. Our findings identified the population genetic basis of domesticated sheep at the whole-genome level, providing theoretical insights into the molecular mechanism underlying breed characteristics and phenotypic changes during sheep domestication and improvement.展开更多
Grape berry shape is an important agricultural trait.Clarifying its genetic basis is significant for cultivating grape varieties that meet market demands.However,the current study by forward genetics has not achieved ...Grape berry shape is an important agricultural trait.Clarifying its genetic basis is significant for cultivating grape varieties that meet market demands.However,the current study by forward genetics has not achieved in-depth results.Here,a high-density map was constructed to identify quantitative trait loci(QTLs)for berry shape.A total of 358709 polymorphic SNPs were obtained using whole-genome resequencing(WGS)based on 208 F2 individuals derived from round grape‘E42-6’and oblong grape‘Rizamat’.The 1635.65 cM high-density map was divided into 19 linkage groups with an average distance of 0.37 cM.Using this map,three significant QTLs for fruit shape index(ShI:ratio of berry length to berry width)identified over three years were mapped onto LG4 and LG5,including one stable QTL on Chr5 with the genomic region of 0.47–1.94 Mb.Combining with gene annotation and expression patterns based on RNA-seq data from two contrasting F2 individuals with round and oblong berry(their average ShI was 1.89 and 1.10,respectively)at four developmental stages,four candidate genes were selected from the above QTLs.They were mainly involved in DNA replication,cell wall modification,and phytohormone biosynthesis.Further analysis of RNA-seq data revealed that several important phytohormone synthesis and metabolic pathways were enriched based on differentially expressed genes(DEGs),which was consistent with the results of QTL mapping for genes related to plant hormone biosynthesis in the F2 population.Furthermore,a comparison of plant hormone content showed that there were significant differences in IAA and tZ content between the two contrasting F2 individuals at different developmental stages.Our findings provide molecular insights into the genetic variation in grape berry shape.Stable QTLs and their tightly linked markers offer the possibility of marker-assisted selection to accelerate berry shape breeding.展开更多
We performed a genome-wide scan to detect selection signatures that showed evidence of positive selection in the domestication process by re-sequencing the whole genomes of Landrace and Yorkshire pigs.Fifteen annotate...We performed a genome-wide scan to detect selection signatures that showed evidence of positive selection in the domestication process by re-sequencing the whole genomes of Landrace and Yorkshire pigs.Fifteen annotated elements with 13 associated genes were identified using the Z-transformed FST(Z(FST))method,and 208 annotated elements with 140 associated genes were identified using the Z-transformed heterozygosity(ZHp)method.The functional analysis and the results of previous studies showed that most of the candidate genes were associated with basic metabolism,disease resistance,cellular processes,and biochemical signals,and several were related to body morphology and organs.They included PPP3CA,which plays an essential role in the transduction of intracellular Ca2+-mediated signals,and WWTR1,which plays a pivotal role in organ size control and tumor suppression.These results suggest that genes associated with body morphology were subject to selection pressure during domestication,whereas genes involved in basic metabolism and disease resistance were subject to selection during artificial breeding.Our findings provide new insights into the potential genetic variation of phenotypic diversity in different pig breeds and will help to better understand the selection effects of modern breeding in Landrace and Yorkshire pigs.展开更多
Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of th...Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.展开更多
BACKGROUND Gastric cancer(GC), a multifactorial disease, is caused by pathogens, such as Helicobacter pylori(H. pylori) and Epstein-Barr virus(EBV), and genetic components.AIM To investigate microbiomes and host genom...BACKGROUND Gastric cancer(GC), a multifactorial disease, is caused by pathogens, such as Helicobacter pylori(H. pylori) and Epstein-Barr virus(EBV), and genetic components.AIM To investigate microbiomes and host genome instability by cost-effective,low-coverage wholegenome sequencing,as biomarkers for GC subtyping.METHODS Samples from 40 GC patients were collected from Taizhou Hospital,Zhejiang Province,affiliated with Wenzhou Medical University.DNA from the samples was subjected to low-coverage wholegenome sequencing with a median genome coverage of 1.86×(range:1.03×to 3.17×) by Illumina×10,followed by copy number analyses using a customized bioinformatics workflow ultrasensitive chromosomal aneuploidy detector.RESULTS Of the 40 GC samples,20 (50%) were found to be enriched with microbiomes.EBV DNA was detected in 5 GC patients (12.5%).H.pylori DNA was found in 15 (37.5%) patients.The other 20(50%) patients were found to have relatively higher genomic instability.Copy number amplifications of the oncogenes,ERBB2 and KRAS,were found in 9 (22.5%) and 7 (17.5%) of the GC samples,respectively.EBV enrichment was found to be associated with tumors in the gastric cardia and fundus.H.pylori enrichment was found to be associated with tumors in the pylorus and antrum.Tumors with elevated genomic instability showed no localization and could be observed in any location.Additionally,H.pylori-enriched GC was found to be associated with the Borrmann type Ⅱ/Ⅲ and gastritis history.EBV-enriched GC was not associated with gastritis.No statistically significant correlation was observed between genomic instability and gastritis.Furthermore,these three different molecular subtypes showed distinct survival outcomes (P=0.019).EBV-positive tumors had the best prognosis,whereas patients with high genomic instability (CIN+) showed the worst survival.Patients with H.pylori infection showed intermediate prognosis compared with the other two subtypes.CONCLUSION Thus,using low-coverage whole-genome sequencing,GC can be classified into three categories based on disease etiology;this classification may prove useful for GC diagnosis and precision medicine.展开更多
The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independ...The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independently reported in two Asian primate research centers.Nevertheless,the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated.Here,we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing.We identified 14558184 single nucleotide polymorphisms(SNPs)from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples.Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers.In addition,SNP and copy number variation(CNV)analyses suggested that the WW domain-containing oxidoreductase(WWOX)and Tyrosine-protein phosphatase nonreceptor type 21(PTPN21)genes may be associated with epilepsy in marmosets.Notably,KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets.This study provides valuable population genomic resources for marmosets in two Asian primate centers.Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers,while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.展开更多
Background:Hundreds of single-nucleotide polymorphism(SNP)sites have been found to be potential genetic markers of type 2 diabetes mellitus(T2DM).However,SNPs related to T2DM in minipigs have been less reported.This s...Background:Hundreds of single-nucleotide polymorphism(SNP)sites have been found to be potential genetic markers of type 2 diabetes mellitus(T2DM).However,SNPs related to T2DM in minipigs have been less reported.This study aimed to screen the T2DM-susceptible candidate SNP loci in Bama minipigs so as to improve the success rate of the minipig T2DM model.Methods:The genomic DNAs of three Bama minipigs with T2DM,six sibling lowsusceptibility minipigs with T2DM,and three normal control minipigs were compared by whole-genome sequencing.The T2DM Bama minipig-specific loci were obtained,and their functions were annotated.Meanwhile,the Biomart software was used to perform homology alignment with T2DM-related loci obtained from the human genome-wide association study to screen candidate SNP markers for T2DM in Bama miniature pigs.Results:Whole-genome resequencing detected 6960 specific loci in the minipigs with T2DM,and 13 loci corresponding to 9 diabetes-related genes were selected.Further,a set of 122 specific loci in 69 orthologous genes of human T2DM candidate genes were obtained in the pigs.Collectively,a batch of T2DM-susceptible candidate SNP markers in Bama minipigs,covering 16 genes and 135 loci,was established.Conclusions:Whole-genome sequencing and comparative genomics analysis of the orthologous genes in pigs that corresponded to the human T2DM-related variant loci successfully screened out T2DM-susceptible candidate markers in Bama miniature pigs.Using these loci to predict the susceptibility of the pigs before constructing an animal model of T2DM may help to establish an ideal animal model.展开更多
Sheep(Ovis aries),among the first domesticated species,are now globally widespread and exhibit remarkable adaptability to diverse environments.In this study,we perform whole-genome sequencing of266 animals from 18 dis...Sheep(Ovis aries),among the first domesticated species,are now globally widespread and exhibit remarkable adaptability to diverse environments.In this study,we perform whole-genome sequencing of266 animals from 18 distinct Chinese sheep populations,each displaying unique phenotypes indicative of adaptation to varying environmental conditions.Integrating 131 environmental factors with single nucleotide polymorphism variations,we conduct a comprehensive genetic-environmental association analysis.This analysis identifies 35 key genes likely integral to the environmental adaptation of sheep.The functions of these genes include fat tail formation(HOXA10,HOXA11,JAZF1),wool characteristics(FER,FGF5,MITF,PDE4B),horn phenotypes(RXFP2),reproduction(HIBADH,TRIM71,C6H4orf22),and growth traits(ADGRL3,TRHDE).Notably,we observe a significant correlation between the frequency of missense mutations in the PAPSS2 and RXFP2 genes and variations in altitude.Our study reveals candidate genes for adaptive variation in sheep and demonstrates the diversity in how sheep adapt to their environment.展开更多
Background Long-term natural and artificial selection has resulted in many genetic footprints within the genomes of pig breeds across distinct agroecological zones.Nevertheless,the mechanisms by which these signatures...Background Long-term natural and artificial selection has resulted in many genetic footprints within the genomes of pig breeds across distinct agroecological zones.Nevertheless,the mechanisms by which these signatures contribute to phenotypic diversity and facilitate environmental adaptation remain unclear.Results Here,we leveraged whole-genome sequencing data from 82 individuals from 6 domestic pig breeds originating in tropical,high-altitude,and frigid regions.Population genetic analysis suggested that habitat isolation significantly shaped the genetic diversity and contributed to population stratification in local Chinese pig breeds.Analysis of selection signals revealed regions under selection for adaptation in tropical(55.5 Mb),high-altitude(43.6 Mb),and frigid(17.72 Mb)regions.The potential functions of the selective sweep regions were linked to certain complex traits that might play critical roles in different geographic environments,including fat coverage in frigid environments and blood indicators in tropical and high-altitude environments.Candidate genes under selection were significantly enriched in biological pathways involved in environmental adaptation.These pathways included blood circulation,protein degradation,and inflammation for adaptation to tropical environments;heart and lung development,hypoxia response,and DNA damage repair for high-altitude adaptation;and thermogenesis,cold-induced vasodilation(CIVD),and the cell cycle for adaptation to frigid environments.By examining the chromatin state of the selection signatures,we identified the lung and ileum as two candidate functional tissues for environmental adaptation.Finally,we identified a mutation(chr1:G246,175,129A)in the cis-regulatory region of ABCA1 as a plausible promising variant for adaptation to tropical environments.Conclusions In this study,we conducted a genome-wide exploration of the genetic mechanisms underlying the adaptability of local Chinese pig breeds to tropical,high-altitude,and frigid environments.Our findings shed light on the prominent role of cis-regulatory elements in environmental adaptation in pigs and may serve as a valuable biological model of human plateau-related disorders and cardiovascular diseases.展开更多
The leopard coral grouper(Plectropomus leopardus)is a species of significant economic importance.Although artificial cultivation of P.leopardus has thrived in recent decades,the advancement of selective breeding has b...The leopard coral grouper(Plectropomus leopardus)is a species of significant economic importance.Although artificial cultivation of P.leopardus has thrived in recent decades,the advancement of selective breeding has been hindered by the lack of comprehensive population genomic data.In this study,we identified over 8.73 million single nucleotide polymorphisms(SNPs)through whole-genome resequencing of 326 individuals spanning six distinct groups.Furthermore,we categorized 226 individuals with high-coverage sequencing depth(≥14×)into eight clusters based on their genetic profiles and phylogenetic relationships.Notably,four of these clusters exhibited pronounced genetic differentiation compared with the other populations.To identify potentially advantageous loci for P.leopardus,we examined genomic regions exhibiting selective sweeps by analyzing the nucleotide diversity(θπ)and fixation index(FST)in these four clusters.Using these high-coverage resequencing data,we successfully constructed the first haplotype reference panel specific to P.leopardus.This achievement holds promise for enabling high-quality,cost-effectiveimputationmethods.Additionally,we combined low-coverage sequencing data with imputation techniques for a genome-wide association study,aiming to identify candidate SNP loci and genes associated with growth traits.A significant concentration of these genes was observed on chromosome 17,which is primarily involved in skeletal muscle and embryonic development and cell proliferation.Notably,our detailed investigation of growth-related SNPs across the eight clusters revealed that cluster 5 harbored the most promising candidate SNPs,showing potential for genetic selective breeding efforts.These findings provide a robust toolkit and valuable insights into the management of germplasm resources and genome-driven breeding initiatives targeting P.leopardus.展开更多
To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic an...To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic analysis and bivariate whole-genome linkage scan were carried out in a large Caucasian population. All the phenotypes studied were significantly controlled by genetic factors （P 〈 0.001） with the heritabilities ranging from 0.45 to 0.68. Significantly genetic correlations were found between TBFM and CSA （cross-section area）, W （sub-periosteal diameter）, Z （section modulus） and CT （cortical thickness） except between TBFM and BR （buckling ratio）. The peak bivariate LOD scores were 3.23 （20q12）, 2.47 （20p11）, 3.19 （6q27）, 1.68 （20p12）, and 2.47 （7q11） for the five pairs of TBFM and BR, CSA, CT, W, and Z in the entire sample, respectively. Gender-specific bivariate linkage evidences were also found for the five pairs. 6p25 had complete pleiotropic effects on the variations of TBFM ＆ Z in the female sub-population, and 6q27 and 17q11 had coincident link- ages for TBFM ＆ CSA and TBFM ＆ Z in the entire population. We identified moderate genetic correlations and several shared genomic regions between TBFM and FNGPs in a large Caucasian population.展开更多
Objective: The increase in the development of resistance to multiple drugs in mycobacterium tuberculosis(MTB) poses a substantial obstacle to the prevention and management of tuberculosis(TB). A thorough investigation...Objective: The increase in the development of resistance to multiple drugs in mycobacterium tuberculosis(MTB) poses a substantial obstacle to the prevention and management of tuberculosis(TB). A thorough investigation of the genotypes linked to multidrug resistance is crucial for comprehending the mechanisms underlying drug resistance. The objective of this research was to assess the attributes of gene mutations associated with multidrug resistance in clinical isolates of mycobacterium tuberculosis through the utilization of whole-genome sequencing. Methods: A total of 124 strains of drug-resistant mycobacterium tuberculosis were collected, and the genomic DNA of both multidrug-resistant and rifampin-resistant strains were extracted and sequenced. Bioinformatics was used to analyze and compare multidrug resistance-related gene sequences in order to detect the variation of multidrug resistance genes. Results: The results revealed that the resistance spectrum of XDR-TB group was much wider than that of the other three groups, with the RR-TB group having the most limited resistance spectrum.Within the MDR-TB strains, fabG1 exhibited the highest frequency of mutations, while RRS, gyrA, and rpoB were identified as the predominant mutation bases in XDR-TB strains. Additionally, rpoB emerged as the primary mutation base in MDR-TB and RR-TB strains. Notably, the fabG1 mutation was found to be closely associated with PDR-TB. Furthermore, the correlation between the mutation rate of rpoB and multidrug resistance was deemed to be of secondary importance. Conclusion: Various strains of MTB exhibited distinct mechanisms of drug resistance, with the gene mutations of fabG1,RRS, gyrA, and rpoB potentially playing a pivotal role in the development of drug resistance. However, the primary genes responsible for drug resistance mutations varied among different strains of TB.展开更多
Rosids,comprising 90,000–120,000 species,form a large clade of angiosperms,including extensively studied families with many economically and scientifically important plants.They are also ecologically important,domina...Rosids,comprising 90,000–120,000 species,form a large clade of angiosperms,including extensively studied families with many economically and scientifically important plants.They are also ecologically important,dominating many temperate and tropical ecosystems.Great progress in understanding rosid phylogenetic relationships has facilitated evolutionary studies,but phylogenetic uncertainties remain.To construct a more comprehensive nuclear phylogeny with expanded taxon coverage at the familial levels,we generated203 new transcriptomes and two shotgun genomes.Along with other available data sets,our sample includes 419 eudicots,including 316 rosids,representing 83 families and all 16 rosid orders.Compared to the 1KP study,our highly resolved rosid phylogeny provides strongly supported internal relationships for one additional order and 16 families.We uncovered cytoplasmicnuclear discordance for several deep rosid relationships with possible evidence of hybridization/gene flow and incomplete lineage sorting.By tracing ancestral states of morphological characters,we revealed putative floral evolutionary trends in some major clades.We detected strong evidence for 27 putative whole-genome duplication(WGD)events distributed across 20 rosid families,including five novel WGDs.Additionally,our expanded taxon sampling allowed for revised phylogenetic positions of several previously reported WGD events.Most of the supported WGDs correspond to origins of families or large subclades and occurred near times of geological and global climate upheavals,including those at the Cretaceous–Paleogene boundary.Our findings support the idea that large-scale genomic changes and key morphological innovations might have contributed to adaptive evolution and increased biodiversity in rosids.展开更多
Gayal(Bos frontalis)an endangered bovine species inhabitingChina,India,Bangladesh,Myanmar and Bhutan,has a mysterious evolutionary origin.Shaped by natural selection,its unique traits make it a valuable genetic resour...Gayal(Bos frontalis)an endangered bovine species inhabitingChina,India,Bangladesh,Myanmar and Bhutan,has a mysterious evolutionary origin.Shaped by natural selection,its unique traits make it a valuable genetic resource;however,its populations are rapidly declining.In this study,comprehensive whole-genome resequencing of fiftyeight samples of Gayal from China,India,Myanmar and Bangladesh was performed.We identified over 44 million SNPs across four Gayal populations.Nucleotide diversity analysis revealed variations in genetic diversity,with the lowest occurring in India and the highest occurring in China.Phylogenetic tree analysis revealed three distinct clades representing China,India and Bangladesh-Myanmar,which were further confirmed by principal component and admixture analyses.The genetic exchanges between Gayal and other bovine species indicate limited influence from domestic cattle in both the Chinese and Bangladeshi Gayal populations.Mitochondrial DNA sequences and a phylogenetic tree highlighted the unique mitochondrial genome of Gayal.Genome-wide selection signals pinpointed candidate genes linked to mitochondrial function,immunity,musculoskeletal development,reproduction and growth performance.Distinct haplotype patterns emerged for the CCDC157,KIAA0753 and MTFP1 genes in the Chinese and Bangladesh-Myanmar Gayal populations,indicating artificial selection in the Chinese population.KEGG pathway and gene ontology enrichment analyses provided insights into processes related to neurodevelopment,cardiac function,tissue growth,immunity and metabolism.In summary,our study enhances our understanding of Gayal genetics,population structure and selection signals across four countries.This knowledge is crucial for conserving this endangered species amid its rapid decline.展开更多
基金supported by the National Key R&D Program of China(2022YFF1000100)China Postdoctoral Science Foundation(2022M722615)。
文摘Local cattle breeds play a critical role in breeding programs due to their genetic adaptations to diverse environmental conditions.However,the genomic architecture of local cattle breeds in Kazakhstan remains largely unexplored.This study utilized whole-genome sequencing data from Kazakh cattle to elucidate their genetic composition,uncovering three primary ancestral components:European,Eurasian,and East Asian taurine.The East Asian taurine lineage likely represents the earliest genetic contribution to Kazakh cattle but was largely replaced by subsequent waves of cattle migrations across Eurasia,leaving only a minor genetic signature in the current cattle population.In contrast,Eurasian taurine ancestry predominated in the Alatau and Kazakh local breeds,while the European taurine component was most prevalent in Kazakh white-headed cattle,consistent with their documented breeding history.Kazakh cattle exhibited higher genetic diversity and lower inbreeding coefficients compared to European commercial breeds,reflecting reduced exposure to intense artificial selection.A strong selection signal was identified on chromosome 6 at a locus encompassing PDGFRA,KIT,and KDR,which may be associated with the white-headed pigmentation characteristic of Kazakh white-headed cattle.Additional genes under selection were linked to lipid metabolism(IRS1,PRKG1,and ADCY8),meat production traits(KCNMA1,PDGFRA,HIF1A,and ANTXR1),and dairy production(ATP2B1,DHX15,FUK,NEGR1,CCDC91,COG4,and PTK2B).This study represents the first comprehensive analysis of nuclear genome data from local Kazakh cattle.It highlights the impact of historical cattle migrations across Eurasia on their genetic landscape and identifies key genomic regions under selection.These findings advance our understanding of the evolutionary history of cattle and offer valuable genetic resources for future breeding strategies.
基金supported by the National Basic Research Program of ChinaSpecial Project for National Supercomputing Zhengzhou Center Innovation Ecosystem Construction(201400210600)+4 种基金Outstanding Young Scientists of Henan Academy of Agricultural Sciences(2020YQ08)Fund for Distinguished Young Scholars from Henan Academy of Agricultural Sciences(2019JQ02)China Agriculture Research System(CARS-13)Henan Provincial Agriculture Research System,China(S2012-5)Henan Provincial Young Talents Supporting Project(2020HYTP044)。
文摘Oil and protein content and fatty acid composition are quality traits in peanut.Elucidating the genetic mechanisms underlying these traits may help researchers to obtain improved cultivars by molecular breeding.Whole-genome resequencing of a recombinant inbred population of 318 lines was performed to construct a high-density linkage map and identify QTL for peanut quality.The map,containing 4561 bin markers,covered 2032 c M with a mean marker density of 0.45 c M.A total of 110 QTL for oil and protein content,and fatty acid composition were mapped on the 18 peanut chromosomes.The QTL q A05.1 was detected in four environments and showed a major phenotypic effect on the contents of oil,protein,and six fatty acids.The genomic region spanned by q A05.1,corresponding to a physical interval of approximately 1.5 Mb,contains two SNPs polymorphic between the parents that could cause missense mutations.The two SNP sites were employed as KASP markers and validated using lines with extremely high and low oil contents.These sites may be useful in the marker-assisted breeding of peanut cultivars with high oil contents.
基金supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003 and XDB02030002)the Bureau of Frontier Sciences and Education,Chinese Academy of Sciences (QYZDJ-SSW-SMC005)+3 种基金the National Natural Science Foundation of China (Nos. 81088001,81271484,81471361 and 81371480)the Beijing Training Project for the Leading Talents in S & T (Z151100000315020)the National Key Basic Research and Development Program (973) (2012CB517904)the CAS/SAFEA International Partnership Programme for Creative Research Teams (Y2CX131003)
文摘Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive.We implemented whole-genome sequencing(WGS) analysis of 8 families with monozygotic(MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations(DNMs) or inherited variants with susceptibility to schizophrenia. Eight non-synonymous DNMs(including one splicing site) were identified and shared by twins, which were either located in previously reported schizophrenia risk genes(p.V24689 I mutation in TTN, p.S2506 T mutation in GCN1L1, IVS3+1G > T in DOCK1) or had a benign to damaging effect according to in silico prediction analysis. By searching the inherited rare damaging or loss-of-function(LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes, we were able to distill genetic alterations in several schizophrenia risk genes, including GAD1, PLXNA2, RELN and FEZ1. Four inherited copy number variations(CNVs; including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families, respectively. Most of families carried both missense DNMs and inherited risk variants, which might suggest that DNMs, inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility. Our results support that schizophrenia is caused by a combination of multiple genetic factors, with each DNM/variant showing a relatively small effect size.
基金supported by the National Key Research and Development Program of China(2021YFD1300901,2022YFD1302000)National Natural Science Foundation of China(32260818,31960653)。
文摘The phenotypic diversity resulting from artificial or natural selection of sheep has made a significant contribution to human civilization.Hu sheep are a local sheep breed unique to China with high reproductive rates and rapid growth.Genomic selection signatures have been widely used to investigate the genetic mechanisms underlying phenotypic variation in livestock.Here,we conduct whole-genome sequencing of 207 Hu sheep and compare them with the wild ancestors of domestic sheep(Asiatic mouflon)to investigate the genetic characteristics and selection signatures of Hu sheep.Based on six signatures of selection approaches,we detect genomic regions containing genes related to reproduction(BMPR1B,BMP2,PGFS,CYP19,CAMK4,GGT5,and GNAQ),vision(ALDH1A2,SAG,and PDE6B),nervous system(NAV1),and immune response(GPR35,SH2B2,PIK3R3,and HRAS).Association analysis with a population of 1299 Hu sheep reveals that those missense mutations in the GPR35(GPR35 g.952651 A>G;GPR35 g.952496 C>T)and NAV1(NAV1 g.84216190 C>T;NAV1 g.84227412 G>A)genes are significantly associated(P<0.05)with immune and growth traits in Hu sheep,respectively.This research offers unique insights into the selection characteristics of Hu sheep and facilitates further genetic improvement and molecular investigations.
基金supported by the grants from the Major State Basic Research Development Program of China(2012CB517902 and 2012CB517904)National Key Technology Research and Development Program of China(2012BAI03B00)+3 种基金Special Research Program of National Health and Family Planning Commission of China(201302002)International S&T Cooperation Program of China(2011DFA30670)National Natural Science Foundation of China(31571357/31771404)supported in part by research funding from AstraZeneca Innovation Center China and Wenzhou Medical University
文摘Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity.In this study,we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD,including de novo mutations,inherited variants,copy number variants (CNVs) and genomic structural variants.A higher mutation rate (Poisson test,P<2.2×10^(-16)) in exonic (1.37×10^(-8)) and 3'-UTR regions (1.42×10^(-8)) was revealed in comparison with that of whole genome (1.05×10^(-8)).Using an integrated model,we identified 87 potentially risk genes (P<0.01) from 4832 genes harboring various rare deleterious variants,including CHD8 and NRXN2,implying that the disorders may be in favor to multiple-hit.In particular,frequent rare inherited mutations of several microcephaly-associated genes (ASPM,WDR62,and ZNF335)were found in ASD.In chromosomal structure analyses,we found four de novo CNVs and one de novo chromosomal rearrangement event,including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1,which causes Angelman syndrome and microcephaly,and a disrupted TNR due to de novo chromosomal translocation t (1;5) (q25.1;q33.2).Taken together,our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD.Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders,such as ASD,could provide novel insights into pathogenesis,diagnosis and treatment.
基金supported by the Key-Area Research and Development Program of Guangdong Province(2021B0202020001)China Agriculture Research System of MOF and MARA(CARS-46)+2 种基金Central Public-interest Scientific Institution Basal Research Fund of CAFS(2020TD23,2020ZJTD-02)Project of Construction of Guangdong Aquatic Seed Industry Demonstration Base 2021Special Funds for Science Technology Innovation and Industrial Development of Shenzhen Dapeng New District(KJYF202101-02)。
文摘Largemouth bass(Micropterus salmoides) is an economically important fish species in North America, Europe, and China. Various genetic improvement programs and domestication processes have modified its genome sequence through selective pressure, leaving nucleotide signals that can be detected at the genomic level. In this study,we sequenced 149 largemouth bass fish, including protospecies(imported from the US) and improved breeds(four domestic breeding populations from China). We detected genomic regions harboring certain genes associated with improved traits, which may be useful molecular markers for practical domestication, breeding, and selection. Subsequent analyses of genetic diversity and population structure revealed that the improved breeds have undergone more rigorous genetic changes. Through selective signal analysis, we identified hundreds of putative selective sweep regions in each largemouth bass line. Interestingly, we predicted 103 putative candidate genes potentially subjected to selection,including several associated with growth(psst1 and grb10), early development(klf9, sp4, and sp8), and immune traits(pkn2, sept2, bcl6, and ripk2). These candidate genes represent potential genomic landmarks that could be used to improve important traits of biological and commercial interest. In summary, this study provides a genome-wide map of genetic variations and selection footprints in largemouth bass, which may benefit genetic studies and accelerate genetic improvement of this economically important fish.
基金supported by the National Key R&D Program of China (2021YFD1300901)National Natural Science Foundation of China (31960653)+1 种基金West Light Foundation of the Chinese Academy of SciencesNational Joint Research on Improved Breeds of Livestock and Poultry (19210365)。
文摘The abundance of domesticated sheep varieties and phenotypes is largely the result of long-term natural and artificial selection. However, there is limited information regarding the genetic mechanisms underlying phenotypic variation induced by the domestication and improvement of sheep. In this study, to explore genomic diversity and selective regions at the genome level, we sequenced the genomes of 100 sheep across 10 breeds and combined these results with publicly available genomic data from 225 individuals, including improved breeds, Chinese indigenous breeds,African indigenous breeds, and their Asian mouflon ancestor. Based on population structure, the domesticated sheep formed a monophyletic group,while the Chinese indigenous sheep showed a clear geographical distribution trend. Comparative genomic analysis of domestication identified several selective signatures, including IFI44 and IFI44L genes and PANK2 and RNF24 genes, associated with immune response and visual function.Population genomic analysis of improvement demonstrated that candidate genes of selected regions were mainly associated with pigmentation,energy metabolism, and growth development.Furthermore, the IFI44 and IFI44L genes showed a common selection signature in the genomes of 30domesticated sheep breeds. The IFI44 c. 54413058C>G mutation was selected for genotyping and population genetic validation. Results showed that the IFI44 polymorphism was significantly associated with partial immune traits. Our findings identified the population genetic basis of domesticated sheep at the whole-genome level, providing theoretical insights into the molecular mechanism underlying breed characteristics and phenotypic changes during sheep domestication and improvement.
基金financially supported by National Key R&D Program of China(Grant No.2019YFD1001401)Project of Construction of Grape Germplasm Resources Sharing Platform(Grant No.PT2029)+2 种基金Zhengzhou Major Scientific and Technological Innovation Projects(Grant No.2020CXZX0082)National Modern Agricultural Industry Technology System Construction Special Project(Grant No.CARS-29-yc-1)Special Project of Science,Technology Innovation Project of Chinese Academy of Agricultural Sciences(Grant No.CAAS-ASTIP-2019-ZFRI).
文摘Grape berry shape is an important agricultural trait.Clarifying its genetic basis is significant for cultivating grape varieties that meet market demands.However,the current study by forward genetics has not achieved in-depth results.Here,a high-density map was constructed to identify quantitative trait loci(QTLs)for berry shape.A total of 358709 polymorphic SNPs were obtained using whole-genome resequencing(WGS)based on 208 F2 individuals derived from round grape‘E42-6’and oblong grape‘Rizamat’.The 1635.65 cM high-density map was divided into 19 linkage groups with an average distance of 0.37 cM.Using this map,three significant QTLs for fruit shape index(ShI:ratio of berry length to berry width)identified over three years were mapped onto LG4 and LG5,including one stable QTL on Chr5 with the genomic region of 0.47–1.94 Mb.Combining with gene annotation and expression patterns based on RNA-seq data from two contrasting F2 individuals with round and oblong berry(their average ShI was 1.89 and 1.10,respectively)at four developmental stages,four candidate genes were selected from the above QTLs.They were mainly involved in DNA replication,cell wall modification,and phytohormone biosynthesis.Further analysis of RNA-seq data revealed that several important phytohormone synthesis and metabolic pathways were enriched based on differentially expressed genes(DEGs),which was consistent with the results of QTL mapping for genes related to plant hormone biosynthesis in the F2 population.Furthermore,a comparison of plant hormone content showed that there were significant differences in IAA and tZ content between the two contrasting F2 individuals at different developmental stages.Our findings provide molecular insights into the genetic variation in grape berry shape.Stable QTLs and their tightly linked markers offer the possibility of marker-assisted selection to accelerate berry shape breeding.
基金supported by the grants from the Sichuan Science and Technology Program,China(2020YFN0024)the earmarked fund for the China Agriculture Research System(CARS-35-01A)+2 种基金the National Key R&D Program of China(2018YFD0501204)the National Natural Science Foundation of China(C170102)the Sichuan Innovation Team of Pig,China(sccxtd-2021-08)。
文摘We performed a genome-wide scan to detect selection signatures that showed evidence of positive selection in the domestication process by re-sequencing the whole genomes of Landrace and Yorkshire pigs.Fifteen annotated elements with 13 associated genes were identified using the Z-transformed FST(Z(FST))method,and 208 annotated elements with 140 associated genes were identified using the Z-transformed heterozygosity(ZHp)method.The functional analysis and the results of previous studies showed that most of the candidate genes were associated with basic metabolism,disease resistance,cellular processes,and biochemical signals,and several were related to body morphology and organs.They included PPP3CA,which plays an essential role in the transduction of intracellular Ca2+-mediated signals,and WWTR1,which plays a pivotal role in organ size control and tumor suppression.These results suggest that genes associated with body morphology were subject to selection pressure during domestication,whereas genes involved in basic metabolism and disease resistance were subject to selection during artificial breeding.Our findings provide new insights into the potential genetic variation of phenotypic diversity in different pig breeds and will help to better understand the selection effects of modern breeding in Landrace and Yorkshire pigs.
基金funded by the National Key R&D Program of China [2022YFC2305200]Natural Science Foundation of Xinjiang Uygur Autonomous Region [2021A01D145 and 2022D01A115]Applied Technology Research and Development Programing Project of Kashgar Prefecture [KS2021031 and KS2021034]。
文摘Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.
基金Supported by Program of Taizhou Science and Technology Grant,No.20ywb29Medical Health Science and Technology Project of Zhejiang Province,No.2021PY083+2 种基金Key Technology Research and Development Program of Zhejiang Province,No.2019C03040Open Project Program of Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province,No.21SZDSYS01 and 21SZDSYS09Major Research Program of Taizhou Enze Medical Center Grant,No.19EZZDA2
文摘BACKGROUND Gastric cancer(GC), a multifactorial disease, is caused by pathogens, such as Helicobacter pylori(H. pylori) and Epstein-Barr virus(EBV), and genetic components.AIM To investigate microbiomes and host genome instability by cost-effective,low-coverage wholegenome sequencing,as biomarkers for GC subtyping.METHODS Samples from 40 GC patients were collected from Taizhou Hospital,Zhejiang Province,affiliated with Wenzhou Medical University.DNA from the samples was subjected to low-coverage wholegenome sequencing with a median genome coverage of 1.86×(range:1.03×to 3.17×) by Illumina×10,followed by copy number analyses using a customized bioinformatics workflow ultrasensitive chromosomal aneuploidy detector.RESULTS Of the 40 GC samples,20 (50%) were found to be enriched with microbiomes.EBV DNA was detected in 5 GC patients (12.5%).H.pylori DNA was found in 15 (37.5%) patients.The other 20(50%) patients were found to have relatively higher genomic instability.Copy number amplifications of the oncogenes,ERBB2 and KRAS,were found in 9 (22.5%) and 7 (17.5%) of the GC samples,respectively.EBV enrichment was found to be associated with tumors in the gastric cardia and fundus.H.pylori enrichment was found to be associated with tumors in the pylorus and antrum.Tumors with elevated genomic instability showed no localization and could be observed in any location.Additionally,H.pylori-enriched GC was found to be associated with the Borrmann type Ⅱ/Ⅲ and gastritis history.EBV-enriched GC was not associated with gastritis.No statistically significant correlation was observed between genomic instability and gastritis.Furthermore,these three different molecular subtypes showed distinct survival outcomes (P=0.019).EBV-positive tumors had the best prognosis,whereas patients with high genomic instability (CIN+) showed the worst survival.Patients with H.pylori infection showed intermediate prognosis compared with the other two subtypes.CONCLUSION Thus,using low-coverage whole-genome sequencing,GC can be classified into three categories based on disease etiology;this classification may prove useful for GC diagnosis and precision medicine.
基金supported by the National Natural Science Foundation of China (82001372)National Key Research and Development Program of China (2018YFE0126700)+3 种基金Shanghai Jiao Tong University 2030 Initiative (WH510363001-7)Shanghai Municipal Commission of Science and Technology Program (21dz2210100)Shanghai Education Commission Research and Innovation Program (2019-01-07-00-02-E00037)a National Institutes of Health (NIH)grant (5R01HG002385)to E.E.E。
文摘The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independently reported in two Asian primate research centers.Nevertheless,the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated.Here,we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing.We identified 14558184 single nucleotide polymorphisms(SNPs)from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples.Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers.In addition,SNP and copy number variation(CNV)analyses suggested that the WW domain-containing oxidoreductase(WWOX)and Tyrosine-protein phosphatase nonreceptor type 21(PTPN21)genes may be associated with epilepsy in marmosets.Notably,KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets.This study provides valuable population genomic resources for marmosets in two Asian primate centers.Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers,while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.
基金National Natural Science Foundation of China,Grant/Award Number:3147205731802021.Specialized Research Fund for Laboratory Animal Science of PLA,Grant/Award Number:SYDW[2020]01SYDW[2020]02.
文摘Background:Hundreds of single-nucleotide polymorphism(SNP)sites have been found to be potential genetic markers of type 2 diabetes mellitus(T2DM).However,SNPs related to T2DM in minipigs have been less reported.This study aimed to screen the T2DM-susceptible candidate SNP loci in Bama minipigs so as to improve the success rate of the minipig T2DM model.Methods:The genomic DNAs of three Bama minipigs with T2DM,six sibling lowsusceptibility minipigs with T2DM,and three normal control minipigs were compared by whole-genome sequencing.The T2DM Bama minipig-specific loci were obtained,and their functions were annotated.Meanwhile,the Biomart software was used to perform homology alignment with T2DM-related loci obtained from the human genome-wide association study to screen candidate SNP markers for T2DM in Bama miniature pigs.Results:Whole-genome resequencing detected 6960 specific loci in the minipigs with T2DM,and 13 loci corresponding to 9 diabetes-related genes were selected.Further,a set of 122 specific loci in 69 orthologous genes of human T2DM candidate genes were obtained in the pigs.Collectively,a batch of T2DM-susceptible candidate SNP markers in Bama minipigs,covering 16 genes and 135 loci,was established.Conclusions:Whole-genome sequencing and comparative genomics analysis of the orthologous genes in pigs that corresponded to the human T2DM-related variant loci successfully screened out T2DM-susceptible candidate markers in Bama miniature pigs.Using these loci to predict the susceptibility of the pigs before constructing an animal model of T2DM may help to establish an ideal animal model.
基金supported by the National Natural Science Foundation of China(32222079,31961143021)the earmarked fund for the Modern Agro-industry Technology Research System(CARS-39-01)+1 种基金the Science and Technology Innovation Project of the Chinese Academy of Agricultural Sciences(ASTIP-IAS01)National Key Research and Development Program of China(2022YFF1000104-3)。
文摘Sheep(Ovis aries),among the first domesticated species,are now globally widespread and exhibit remarkable adaptability to diverse environments.In this study,we perform whole-genome sequencing of266 animals from 18 distinct Chinese sheep populations,each displaying unique phenotypes indicative of adaptation to varying environmental conditions.Integrating 131 environmental factors with single nucleotide polymorphism variations,we conduct a comprehensive genetic-environmental association analysis.This analysis identifies 35 key genes likely integral to the environmental adaptation of sheep.The functions of these genes include fat tail formation(HOXA10,HOXA11,JAZF1),wool characteristics(FER,FGF5,MITF,PDE4B),horn phenotypes(RXFP2),reproduction(HIBADH,TRIM71,C6H4orf22),and growth traits(ADGRL3,TRHDE).Notably,we observe a significant correlation between the frequency of missense mutations in the PAPSS2 and RXFP2 genes and variations in altitude.Our study reveals candidate genes for adaptive variation in sheep and demonstrates the diversity in how sheep adapt to their environment.
基金supported by the National Key Research and Development Program of China(2021YFF1000600)the National Natural Science Foundation of China(32002150 and U23A20229)+3 种基金the Basic and Applied Basic Research Foundation of Guangdong Province(2020B1515120053)the Shenzhen Science and Technology Innovation Commission(JCYJ20190813114401691)the Central Government Guiding Funds for Local Science and Technology Development of China(He-Ke ZY220603)the Open Project of Hainan Provincial Key Laboratory of Tropical Animal Reproduction&Breeding and Epidemic Disease Research(HKL2020101)。
文摘Background Long-term natural and artificial selection has resulted in many genetic footprints within the genomes of pig breeds across distinct agroecological zones.Nevertheless,the mechanisms by which these signatures contribute to phenotypic diversity and facilitate environmental adaptation remain unclear.Results Here,we leveraged whole-genome sequencing data from 82 individuals from 6 domestic pig breeds originating in tropical,high-altitude,and frigid regions.Population genetic analysis suggested that habitat isolation significantly shaped the genetic diversity and contributed to population stratification in local Chinese pig breeds.Analysis of selection signals revealed regions under selection for adaptation in tropical(55.5 Mb),high-altitude(43.6 Mb),and frigid(17.72 Mb)regions.The potential functions of the selective sweep regions were linked to certain complex traits that might play critical roles in different geographic environments,including fat coverage in frigid environments and blood indicators in tropical and high-altitude environments.Candidate genes under selection were significantly enriched in biological pathways involved in environmental adaptation.These pathways included blood circulation,protein degradation,and inflammation for adaptation to tropical environments;heart and lung development,hypoxia response,and DNA damage repair for high-altitude adaptation;and thermogenesis,cold-induced vasodilation(CIVD),and the cell cycle for adaptation to frigid environments.By examining the chromatin state of the selection signatures,we identified the lung and ileum as two candidate functional tissues for environmental adaptation.Finally,we identified a mutation(chr1:G246,175,129A)in the cis-regulatory region of ABCA1 as a plausible promising variant for adaptation to tropical environments.Conclusions In this study,we conducted a genome-wide exploration of the genetic mechanisms underlying the adaptability of local Chinese pig breeds to tropical,high-altitude,and frigid environments.Our findings shed light on the prominent role of cis-regulatory elements in environmental adaptation in pigs and may serve as a valuable biological model of human plateau-related disorders and cardiovascular diseases.
基金supported by the National Key Research and Development Program of China (2022YFD2400501)Key R&D Project of Hainan Province (ZDYF2021XDNY133)+2 种基金Project of Sanya Yazhouwan Science and Technology City Management Foundation (SKJC-2020-02-009)PhD Scientific Research and Innovation Foundation of Sanya Yazhou Bay Science and Technology City (HSPHDSRF-2022-02-007)Young Elite Scientists Sponsorship Program by CAST (2023QNRC001)。
文摘The leopard coral grouper(Plectropomus leopardus)is a species of significant economic importance.Although artificial cultivation of P.leopardus has thrived in recent decades,the advancement of selective breeding has been hindered by the lack of comprehensive population genomic data.In this study,we identified over 8.73 million single nucleotide polymorphisms(SNPs)through whole-genome resequencing of 326 individuals spanning six distinct groups.Furthermore,we categorized 226 individuals with high-coverage sequencing depth(≥14×)into eight clusters based on their genetic profiles and phylogenetic relationships.Notably,four of these clusters exhibited pronounced genetic differentiation compared with the other populations.To identify potentially advantageous loci for P.leopardus,we examined genomic regions exhibiting selective sweeps by analyzing the nucleotide diversity(θπ)and fixation index(FST)in these four clusters.Using these high-coverage resequencing data,we successfully constructed the first haplotype reference panel specific to P.leopardus.This achievement holds promise for enabling high-quality,cost-effectiveimputationmethods.Additionally,we combined low-coverage sequencing data with imputation techniques for a genome-wide association study,aiming to identify candidate SNP loci and genes associated with growth traits.A significant concentration of these genes was observed on chromosome 17,which is primarily involved in skeletal muscle and embryonic development and cell proliferation.Notably,our detailed investigation of growth-related SNPs across the eight clusters revealed that cluster 5 harbored the most promising candidate SNPs,showing potential for genetic selective breeding efforts.These findings provide a robust toolkit and valuable insights into the management of germplasm resources and genome-driven breeding initiatives targeting P.leopardus.
基金supported by grants from NIH in USA (No. K01 AR02170-01, R01 AR45349-01, R01 GM60402-01 A1, R01 AG026564-01A2, and R21 AG027110-01A1)the Natural Science Foundation o China (NSFC) (No. 30600364)The genotyping experiment was performed by Marshfield Center for Medical Genetics and supported by NHLB Mammalian Genotyping Service (Contract No. HV48141)
文摘To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic analysis and bivariate whole-genome linkage scan were carried out in a large Caucasian population. All the phenotypes studied were significantly controlled by genetic factors （P 〈 0.001） with the heritabilities ranging from 0.45 to 0.68. Significantly genetic correlations were found between TBFM and CSA （cross-section area）, W （sub-periosteal diameter）, Z （section modulus） and CT （cortical thickness） except between TBFM and BR （buckling ratio）. The peak bivariate LOD scores were 3.23 （20q12）, 2.47 （20p11）, 3.19 （6q27）, 1.68 （20p12）, and 2.47 （7q11） for the five pairs of TBFM and BR, CSA, CT, W, and Z in the entire sample, respectively. Gender-specific bivariate linkage evidences were also found for the five pairs. 6p25 had complete pleiotropic effects on the variations of TBFM ＆ Z in the female sub-population, and 6q27 and 17q11 had coincident link- ages for TBFM ＆ CSA and TBFM ＆ Z in the entire population. We identified moderate genetic correlations and several shared genomic regions between TBFM and FNGPs in a large Caucasian population.
文摘Objective: The increase in the development of resistance to multiple drugs in mycobacterium tuberculosis(MTB) poses a substantial obstacle to the prevention and management of tuberculosis(TB). A thorough investigation of the genotypes linked to multidrug resistance is crucial for comprehending the mechanisms underlying drug resistance. The objective of this research was to assess the attributes of gene mutations associated with multidrug resistance in clinical isolates of mycobacterium tuberculosis through the utilization of whole-genome sequencing. Methods: A total of 124 strains of drug-resistant mycobacterium tuberculosis were collected, and the genomic DNA of both multidrug-resistant and rifampin-resistant strains were extracted and sequenced. Bioinformatics was used to analyze and compare multidrug resistance-related gene sequences in order to detect the variation of multidrug resistance genes. Results: The results revealed that the resistance spectrum of XDR-TB group was much wider than that of the other three groups, with the RR-TB group having the most limited resistance spectrum.Within the MDR-TB strains, fabG1 exhibited the highest frequency of mutations, while RRS, gyrA, and rpoB were identified as the predominant mutation bases in XDR-TB strains. Additionally, rpoB emerged as the primary mutation base in MDR-TB and RR-TB strains. Notably, the fabG1 mutation was found to be closely associated with PDR-TB. Furthermore, the correlation between the mutation rate of rpoB and multidrug resistance was deemed to be of secondary importance. Conclusion: Various strains of MTB exhibited distinct mechanisms of drug resistance, with the gene mutations of fabG1,RRS, gyrA, and rpoB potentially playing a pivotal role in the development of drug resistance. However, the primary genes responsible for drug resistance mutations varied among different strains of TB.
基金supported by funds from the National Natural Science Foundation of China(32270232,31970224,and 31770242)State Key Laboratory of Reproductive Regulation&Breeding of Grassland Livestock,Key Laboratory of Herbage&Endemic Crop Biology,Ministry of Education(Inner Mongolia University)supported by State Key Laboratory of Genetics and Development of Complex Phenotypes,State Key Laboratory of Wetland Conservation and Restoration,National Observations and Research Station for Wetland Ecosystems of the Yangtze Estuary,Ministry of Education Key Laboratory of Biodiversity Sciences and Ecological Engineering,Human Phenome Data Center(Fudan university)。
文摘Rosids,comprising 90,000–120,000 species,form a large clade of angiosperms,including extensively studied families with many economically and scientifically important plants.They are also ecologically important,dominating many temperate and tropical ecosystems.Great progress in understanding rosid phylogenetic relationships has facilitated evolutionary studies,but phylogenetic uncertainties remain.To construct a more comprehensive nuclear phylogeny with expanded taxon coverage at the familial levels,we generated203 new transcriptomes and two shotgun genomes.Along with other available data sets,our sample includes 419 eudicots,including 316 rosids,representing 83 families and all 16 rosid orders.Compared to the 1KP study,our highly resolved rosid phylogeny provides strongly supported internal relationships for one additional order and 16 families.We uncovered cytoplasmicnuclear discordance for several deep rosid relationships with possible evidence of hybridization/gene flow and incomplete lineage sorting.By tracing ancestral states of morphological characters,we revealed putative floral evolutionary trends in some major clades.We detected strong evidence for 27 putative whole-genome duplication(WGD)events distributed across 20 rosid families,including five novel WGDs.Additionally,our expanded taxon sampling allowed for revised phylogenetic positions of several previously reported WGD events.Most of the supported WGDs correspond to origins of families or large subclades and occurred near times of geological and global climate upheavals,including those at the Cretaceous–Paleogene boundary.Our findings support the idea that large-scale genomic changes and key morphological innovations might have contributed to adaptive evolution and increased biodiversity in rosids.
基金supported by the Yunnan Expert Workstation(202305AF150156)the China Agriculture Research System of MOF and MARA(CARS-37)+1 种基金the Yunling cattle special program of the Yunnan Joint Laboratory of the Seeds and Seeding Industry(202205AR070001)the Construction of the Yunling Cattle Technology Innovation Center and Industrialization of Achievements(2019ZG007).
文摘Gayal(Bos frontalis)an endangered bovine species inhabitingChina,India,Bangladesh,Myanmar and Bhutan,has a mysterious evolutionary origin.Shaped by natural selection,its unique traits make it a valuable genetic resource;however,its populations are rapidly declining.In this study,comprehensive whole-genome resequencing of fiftyeight samples of Gayal from China,India,Myanmar and Bangladesh was performed.We identified over 44 million SNPs across four Gayal populations.Nucleotide diversity analysis revealed variations in genetic diversity,with the lowest occurring in India and the highest occurring in China.Phylogenetic tree analysis revealed three distinct clades representing China,India and Bangladesh-Myanmar,which were further confirmed by principal component and admixture analyses.The genetic exchanges between Gayal and other bovine species indicate limited influence from domestic cattle in both the Chinese and Bangladeshi Gayal populations.Mitochondrial DNA sequences and a phylogenetic tree highlighted the unique mitochondrial genome of Gayal.Genome-wide selection signals pinpointed candidate genes linked to mitochondrial function,immunity,musculoskeletal development,reproduction and growth performance.Distinct haplotype patterns emerged for the CCDC157,KIAA0753 and MTFP1 genes in the Chinese and Bangladesh-Myanmar Gayal populations,indicating artificial selection in the Chinese population.KEGG pathway and gene ontology enrichment analyses provided insights into processes related to neurodevelopment,cardiac function,tissue growth,immunity and metabolism.In summary,our study enhances our understanding of Gayal genetics,population structure and selection signals across four countries.This knowledge is crucial for conserving this endangered species amid its rapid decline.
