Rice grain yield is primarily determined by three key agronomic traits:panicle number,grain number per panicle,and grain weight(GW).However,the inherent tradeoffs among these yield components remain a persistent chall...Rice grain yield is primarily determined by three key agronomic traits:panicle number,grain number per panicle,and grain weight(GW).However,the inherent tradeoffs among these yield components remain a persistent challenge in rice breeding programs.Notably,compared with GW,brown rice weight(BRW)provides a more direct metric associated with actual grain yield potential.In this study,we conducted a two-year replicated genome-wide association study to elucidate the genetic architecture of BRW and identify new loci regulating GW.Among seven consistently detected loci across experimental replicates,four were not co-localized with previously reported genes associated with BRW or GW traits.BRW1.1,one of the four newly identified loci,was found to encode a novel RNA-binding protein.Functional characterization revealed that BRW1.1 acts as a negative regulator of BRW,potentially through modulating mRNA translation processes.Intriguingly,through integrated analysis of mutant phenotypes and haplotype variations,we demonstrated that BRW1.1 mediates the physiological tradeoff between GW and panicle number.This study not only delineates the genetic determinants of BRW but also identifies BRW1.1 as a promising molecular target for breaking the yield component tradeoff in precision rice breeding.展开更多
Seedlessness has always been a valuable quality characteristic of edible grape varieties.Although the production of seedless grapes has been ongoing for decades,the genetic complexity of seedless grapes is not yet ful...Seedlessness has always been a valuable quality characteristic of edible grape varieties.Although the production of seedless grapes has been ongoing for decades,the genetic complexity of seedless grapes is not yet fully understood.Therefore,determining the genetic mechanisms and key regulatory genes of seedless grapes is of great significance for seedless grape breeding and meeting market demands.The emergence of high-throughput analysis software offers greater possibilities for mining genes related to plant organ development.Specifically,to mine a greater number of candidate genes related to grape seed traits,this study used the seed trait parameters analyzed by Tomato Analyzer as the target trait and then used a genome-wide association study(GWAS)to mine candidate genes.In the two-year analysis using principal component analysis(PCA),we extracted five principal components with a cumulative contribution rate of 96.586%.The cumulative contribution rate for component 1 reached 87.352%.Correlation analysis revealed correlation coefficients ranging from 0.54 to 0.98 among the seven basic traits.The GWAS results indicated that 370 SNP loci were significantly correlated with seed traits.These SNP loci were distributed on 18 chromosomes,except for chromosome 4,with most SNP loci distributed on chromosome 18.Based on the physical location of single nucleotide polymorphism(SNP)markers significantly associated with seed-related traits in the grape reference genome,candidate genes are screened within the range of linkage disequilibrium(LD)attenuation distance,both upstream and downstream of the significant SNP loci.These candidate genes were mainly transcription factor-related genes(VvMADS4 and VvMADS5),ubiquitin ligase-related genes(E3 ubiquitin ligase BIG BROTHER),serine/threonine protein kinase-related genes,and carbohydrate metabolism-related genes(Sucrose Synthase 2)and simultaneously controlled multiple(at least two or more)seed traits.These results indicate that seed traits are jointly regulated by some genes involved in seed morphology regulation.In this work,we identified new gene loci related to grape seed traits.Identifying molecular markers closely related to these seed traits is of great significance for breeding seedless grape varieties.展开更多
The genetic mechanism determining amylose content(AC)and its impact on eating and cooking quality(ECQ)of rice is highly complex.To elucidate the genetic basis of AC in rice,the Ting’s core collection was used to iden...The genetic mechanism determining amylose content(AC)and its impact on eating and cooking quality(ECQ)of rice is highly complex.To elucidate the genetic basis of AC in rice,the Ting’s core collection was used to identify novel AC genes/loci through genome-wide association analysis(GWAS)using more than 5.0 million single nucleotide polymorphisms(SNPs).In this study,12 genes related to AC,including the major gene Wx and 11 minor genes,were detected using the EMMAX method.A novel gene,LR,encoding a nucleotide-binding leucine-rich-repeat(LRR)receptor(NLR)family protein,was selected for functional study.When LR was knocked out using CRISPR/Cas9,the AC decreased significantly.Furthermore,the AC in varieties was significantly higher with Haplotype A compared to Haplotypes B and C of LR.Notably,two natural variations,SNP-385(Thr-Hap.A vs Ala-Haps.B and C)and SNP-758(Ser-Hap.A vs Asn-Haps.B and C),in the coding region of LR might play critical roles in regulating AC and serve as potential targets for cultivating rice with diverse amylose contents.展开更多
Alkaline soil is characterized by high soluble salt content,elevated pH levels,and ionic imbalance,all of which collectively intensify the harmful effects of alkaline stress on plants.To gain molecular insights into a...Alkaline soil is characterized by high soluble salt content,elevated pH levels,and ionic imbalance,all of which collectively intensify the harmful effects of alkaline stress on plants.To gain molecular insights into alkaline tolerance(AT),we evaluated 13 AT-related traits in 508 diverse rice accessions from the 3K Rice Germplasm Project at the seedling stage.A total of 2929764,2059114,and 1365868 single nucleotide polymorphisms were used to identify alkaline-tolerance QTLs via genome-wide association studies(GWAS)in the entire population as well as in the xian and geng subpopulations,respectively.Candidate genes and their superior haplotypes were further identified through gene-based association,haplotype analysis,and gene function annotation.In total,99 QTLs were identified for AT by GWAS,and three genes(LOC_Os03g49050 for qSSD3.1,LOC_Os05g48760 for qSKC5,and LOC_Os12g01922 for qSNC12)were selected as the most promising candidate genes.Furthermore,we successfully mined superior alleles of key candidate genes from natural variants associated with AT-related traits.This study identified crucial candidate genes and their favorable alleles for AT traits,laying a foundation for further gene cloning and the development of AT rice varieties via marker-assisted selection.展开更多
Southern corn rust(SCR)is an airborne fungal disease caused by Puccinia polysora Underw.(P.polysora)that adversely impacts maize quality and yields worldwide.Screening for new elite SCR-resistant maize loci or genes h...Southern corn rust(SCR)is an airborne fungal disease caused by Puccinia polysora Underw.(P.polysora)that adversely impacts maize quality and yields worldwide.Screening for new elite SCR-resistant maize loci or genes has the potential to enhance overall resistance to this pathogen.Using phenotypic SCR resistance-related data collected over two years and three geographical environments,a genome-wide association study was carried out in this work,which eventually identified 91 loci that were substantially correlated with SCR susceptibility.These included 13 loci that were significant in at least three environments and overlapped with 74 candidate genes(B73_RefGen_v4).Comparative transcriptomic analyses were then performed to identify the genes related to SCR infection,with 2,586 and 797 differentially expressed genes(DEGs)ultimately being identified in the resistant Qi319and susceptible 8112 inbred lines following P.polysora infection,respectively,including 306 genes common to both lines.Subsequent integrative multi-omics investigations identified four potential candidate SCR response-related genes.One of these genes is ZmHCT9,which encodes the protein hydroxycinnamoyl transferase 9.This gene was up-regulated in susceptible inbred lines and linked to greater P.polysora resistance as confirmed through cucumber mosaic virus(CMV)-based virus induced-gene silencing(VIGS)system-mediated gene silencing.These data provide important insights into the genetic basis of the maize SCR response.They will be useful for for future research on potential genes related to SCR resistance in maize.展开更多
Rice cooking and eating qualities(CEQ)are mainly determined by cooked rice textural parameters and starch physicochemical properties.However,the genetic bases of grain texture and starch properties in rice have not be...Rice cooking and eating qualities(CEQ)are mainly determined by cooked rice textural parameters and starch physicochemical properties.However,the genetic bases of grain texture and starch properties in rice have not been fully understood.We conducted a genome-wide association study for apparent amylose content(AAC),starch pasting viscosities,and cooked rice textural parameters using 279 indica rice accessions from the 3000 Rice Genome Project.We identified 26 QTLs in the whole population and detected single nucleotide polymorphisms(SNPs)with the lowest P-value at the Waxy(Wx)locus for all traits except pasting temperature and cohesiveness.Additionally,we detected significant SNPs at the SUBSTANDARD STARCH GRAIN6(SSG6)locus for AAC,setback(SB),hardness,adhesiveness,chewiness(CHEW),gumminess(GUM),and resilience.We subsequently divided the population using a SNP adjacent to the Waxy locus,and identified 23 QTLs and 12 QTLs in two sub-panels,WxT and WxA,respectively.In these sub-panels,SSG6 was also identified to be associated with pasting parameters,including peak viscosity,hot paste viscosity,cold paste viscosity,and consistency viscosity.Furthermore,a candidate gene encoding monosaccharide transporter 5(OsMST5)was identified to be associated with AAC,breakdown,SB,CHEW,and GUM.In total,39 QTLs were co-localized with known genes or previously reported QTLs.These identified genes and QTLs provide valuable information for genetic manipulation to improve rice CEQ.展开更多
Nitrogen(N)fertilizer application is essential for crop-plant growth and development.Identifying genetic loci associated with N-use efficiency(NUE)could increase wheat yields and reduce environmental pollution caused ...Nitrogen(N)fertilizer application is essential for crop-plant growth and development.Identifying genetic loci associated with N-use efficiency(NUE)could increase wheat yields and reduce environmental pollution caused by overfertilization.We subjected a panel of 389 wheat accessions to N and chlorate(a nitrate analog)treatments to identify quantitative trait loci(QTL)controlling NUE-associated traits at the wheat seedling stage.Genotyping the panel with a 660K single-nucleotide polymorphism(SNP)array,we identified 397 SNPs associated with N-sensitivity index and chlorate inhibition rate.These SNPs were merged into 49 QTL,of which eight were multi-environment stable QTL and 27 were located near previously reported QTL.A set of 135 candidate genes near the 49 QTL included TaBOX(F-box family protein)and TaERF(ethylene-responsive transcription factor).A Tabox mutant was more sensitive to low-N stress than the wild-type plant.We developed two functional markers for Hap 1,the favorable allele of TaBOX.展开更多
Appearance and cooked rice elongation are key quality traits of rice. Although some QTL for these traits have been identified, understanding of the genetic relationship between them remains limited. In the present stu...Appearance and cooked rice elongation are key quality traits of rice. Although some QTL for these traits have been identified, understanding of the genetic relationship between them remains limited. In the present study, large phenotypic variation was observed in 760 accessions from the 3 K Rice Genomes Project for both appearance quality and cooked rice elongation. Most component traits of appearance quality and cooked rice elongation showed significant pairwise correlations, but a low correlation was found between appearance quality and cooked rice elongation. A genome-wide association study identified 74 QTL distributed on all 12 chromosomes for grain length, grain width, length to width ratio, degree of endosperm with chalkiness, rice elongation difference, and elongation index. Thirteen regions containing QTL stably expressed in multiple environments and/or exerting pleiotropic effects on multiple traits were detected. By gene-based association analysis and haplotype analysis, 46 candidate genes, including five cloned genes, and 49 favorable alleles were identified for these 13 QTL. The effect of the candidate gene Wx on rice elongation difference was validated by a transgenic strategy. These results shed light on the genetic bases of appearance quality and cooked rice elongation and provide gene resources for improving rice quality by molecular breeding.展开更多
Porcine carcass traits and organ weights have important economic roles in the swine industry. A total of 576 animals from a Large White×Minzhu intercross population were genotyped using the Illumina PorcineSNP60K...Porcine carcass traits and organ weights have important economic roles in the swine industry. A total of 576 animals from a Large White×Minzhu intercross population were genotyped using the Illumina PorcineSNP60K Beadchip and were phenotyped for 10 traits, speciifcally, backfat thickness （6-7 libs）, carcass length, carcass weight, foot weight, head weight, heart weight, leaf fat weight, liver weight, lung weight and slaughter body weight. The genome-wide association study （GWAS） was assessed by Genome Wide Rapid Association using the mixed model and regression-genomic control approach. A total of 31 single nucleotide polymorphisms （SNPs） （with the most signiifcant SNP being MARC0033464, P value=6.80×10-13） were located in a 9.76-Mb （31.24-41.00 Mb） region on SSC7 and were found to be signiifcantly associated with one or more carcass traits and organ weights. High percentage of phenotypic variance explanation was observed for each trait ranging from 31.21 to 67.42%. Linkage analysis revealed one haplotype block of 495 kb, in which the most signiifcant SNP being MARC0033464 was contained, on SSC7 at complete linkage disequilibrium. Annotation of the pig reference genome suggested 6 genes （GRM4, HMGA1, NUDT3, RPS10, SPDEF and PACSIN1） in this candidate linkage disequilibrium （LD） interval. Functional analysis indicated that the HMGA1 gene presents the prime biological candidate for carcass traits and organ weights in pig, with potential application in breeding programs.展开更多
Fusarium ear rot(FER)is a destructive maize fungal disease worldwide.In this study,three tropical maize populations consisting of 874 inbred lines were used to perform genomewide association study(GWAS)and genomic pre...Fusarium ear rot(FER)is a destructive maize fungal disease worldwide.In this study,three tropical maize populations consisting of 874 inbred lines were used to perform genomewide association study(GWAS)and genomic prediction(GP)analyses of FER resistance.Broad phenotypic variation and high heritability for FER were observed,although it was highly influenced by large genotype-by-environment interactions.In the 874 inbred lines,GWAS with general linear model(GLM)identified 3034 single-nucleotide polymorphisms(SNPs)significantly associated with FER resistance at the P-value threshold of 1×10^(-5),the average phenotypic variation explained(PVE)by these associations was 3%with a range from 2.33%to 6.92%,and 49 of these associations had PVE values greater than 5%.The GWAS analysis with mixed linear model(MLM)identified 19 significantly associated SNPs at the P-value threshold of 1×10^(-4),the average PVE of these associations was 1.60%with a range from 1.39%to 2.04%.Within each of the three populations,the number of significantly associated SNPs identified by GLM and MLM ranged from 25 to 41,and from 5 to 22,respectively.Overlapping SNP associations across populations were rare.A few stable genomic regions conferring FER resistance were identified,which located in bins 3.04/05,7.02/04,9.00/01,9.04,9.06/07,and 10.03/04.The genomic regions in bins 9.00/01 and 9.04 are new.GP produced moderate accuracies with genome-wide markers,and relatively high accuracies with SNP associations detected from GWAS.Moderate prediction accuracies were observed when the training and validation sets were closely related.These results implied that FER resistance in maize is controlled by minor QTL with small effects,and highly influenced by the genetic background of the populations studied.Genomic selection(GS)by incorporating SNP associations detected from GWAS is a promising tool for improving FER resistance in maize.展开更多
The human face is a heritable surface with many complex sensory organs.In recent years,many genetic loci associated with facial features have been reported in different populations,yet there is a lack of studies on th...The human face is a heritable surface with many complex sensory organs.In recent years,many genetic loci associated with facial features have been reported in different populations,yet there is a lack of studies on the Han Chinese population.Here,we report a genome-wide association study of 3D normal human faces of 2,659 Han Chinese with autosegment phenotypes of facial morphology.We identify singlenucleotide polymorphisms(SNPs)encompassing four genomic regions showing significant associations with different facial regions,including SNPs in DENND1 B associated with the chin,SNPs among PISRT1 associated with eyes,SNPs between DCHS2 and SFRP2 associated with the nose,and SNPs in VPS13 B associated with the nose.We replicate 24 SNPs from previously reported genetic loci in different populations,whose candidate genes are DCHS2,SUPT3 H,HOXD1,SOX9,PAX3,and EDAR.These results provide a more comprehensive understanding of the genetic basis of variation in human facial morphology.展开更多
Increasing yield is one of the most important goals in crop breeding. Soybean （Glycine max L. Merr.）, one of the most economically important leguminous seed crops, provides the majority of plant proteins, and more t...Increasing yield is one of the most important goals in crop breeding. Soybean （Glycine max L. Merr.）, one of the most economically important leguminous seed crops, provides the majority of plant proteins, and more than a quarter of the world＇s food and animal feed （Graham and Vance, 2003）. The yield of soybean is finally determined by the number of seeds per unit area, which affected by many characters, such as height, branching number, photosynthesis, seed size, seed number. The number of seeds per pod is taken for one of the critical components that related to yield （You et al., 1995）.展开更多
Wheat grain yield is generally sink-limited during grain filling.The grain-filling rate(GFR)plays a vital role but is poorly studied due to the difficulty of phenotype surveys.This study explored the grain-filling tra...Wheat grain yield is generally sink-limited during grain filling.The grain-filling rate(GFR)plays a vital role but is poorly studied due to the difficulty of phenotype surveys.This study explored the grain-filling traits in a recombinant inbred population and wheat collection using two highly saturated genetic maps for linkage analysis and genome-wide association study(GWAS).Seventeen stable additive quantitative trait loci(QTLs)were identified on chromosomes 1B,4B,and 5A.The linkage interval between IWB19555 and IWB56078 showed pleiotropic effects on GFR_(1),GFR_(max),kernel length(KL),kernel width(KW),kernel thickness(KT),and thousand kernel weight(TKW),with the phenotypic variation explained(PVE)ranging from 13.38%(KW)to 33.69%(TKW).198 significant marker-trait associations(MTAs)were distributed across most chromosomes except for 3D and 4D.The major associated sites for GFR included IWB44469(11.27%),IWB8156(12.56%)and IWB24812(14.46%).Linkage analysis suggested that IWB35850,identified through GWAS,was located in approximately the same region as QGFR_(max)2B.3-11,where two high-confidence candidate genes were present.Two important grain weight(GW)-related QTLs colocalized with grain-filling QTLs.The findings contribute to understanding the genetic architecture of the GFR and provide a basic approach to predict candidate genes for grain yield trait QTLs.展开更多
With recent advances in biotechnology, genome-wide association study （GWAS） has been widely used to identify genetic variants that underlie human complex diseases and traits. In case-control GWAS, typical statistica...With recent advances in biotechnology, genome-wide association study （GWAS） has been widely used to identify genetic variants that underlie human complex diseases and traits. In case-control GWAS, typical statistical strategy is traditional logistical regression （LR） based on single-locus analysis. However, such a single-locus analysis leads to the well-known multiplicity problem, with a risk of inflating type I error and reducing power. Dimension reduction-based techniques, such as principal component-based logistic regression （PC-LR）, partial least squares-based logistic regression （PLS-LR）, have recently gained much attention in the analysis of high dimensional genomic data. However, the perfor- mance of these methods is still not clear, especially in GWAS. We conducted simulations and real data application to compare the type I error and power of PC-LR, PLS-LR and LR applicable to GWAS within a defined single nucleotide polymorphism （SNP） set region. We found that PC-LR and PLS can reasonably control type I error under null hypothesis. On contrast, LR, which is corrected by Bonferroni method, was more conserved in all simulation settings. In particular, we found that PC-LR and PLS-LR had comparable power and they both outperformed LR, especially when the causal SNP was in high linkage disequilibrium with genotyped ones and with a small effective size in simulation. Based on SNP set analysis, we applied all three methods to analyze non-small cell lung cancer GWAS data.展开更多
Genome-wide association study(GWAS)was performed for 16 agronomic traits including nitrogen use efficiency(NUE)and yield-related components using a panel of 190 mainly japonica rice varieties and a set of 38390 single...Genome-wide association study(GWAS)was performed for 16 agronomic traits including nitrogen use efficiency(NUE)and yield-related components using a panel of 190 mainly japonica rice varieties and a set of 38390 single nucleotide polymorphism(SNP)markers.This panel was evaluated under rainfed upland conditions in Madagascar in two consecutive cropping seasons with two contrasted nitrogen input levels.Using another set of five grain traits,we identified previously known genes(GW5,GS3,Awn1 and Glabrous1),thus validating the pertinence and accuracy of our datasets for GWAS.A total of 369 significant associations were detected between SNPs and agronomic traits,gathered into 46 distinct haplotype groups and 28 isolated markers.Few association signals were identified for the complex quantitative trait NUE,however,larger number of quantitative trait loci(QTLs)were detected for its component traits,with 10 and 2 association signals for nitrogen utilization efficiency and nitrogen uptake efficiency,respectively.Several detected association signals co-localized with genes involved in nitrogen transport or nitrogen remobilization within 100 kb.The present study thus confirmed the potential of GWAS to identify candidate genes and new loci associated with agronomic traits.However,because of the quantitative and complex nature of NUE-related traits,GWAS might have not captured a large number of QTLs with limited effects.展开更多
Rib eye muscle area（REMA） is an economically important trait and one of the main selection criteria for breeding in the swine industry. In the genome-wide association study（GWAS）, the Illumina Porcine SNP60 Bead C...Rib eye muscle area（REMA） is an economically important trait and one of the main selection criteria for breeding in the swine industry. In the genome-wide association study（GWAS）, the Illumina Porcine SNP60 Bead Chip containing 62 163 single nucleotide polymorphisms（SNPs） was used to genotype 557 pigs from a porcine Large White×Minzhu intercross population. The REMA（at the 5th–6th, 10th–11th and the last ribs） was measured after slaughtered at the age of（240±7） d for each animal. Association tests between REMA trait and SNPs were performed via the Genome-Wide Rapid Association using the Mixed Model and Regression-Genomic Control（GRAMMAR-GC） approach. From the Ensembl porcine database, SNP annotation was implemented using Sus scrofa Build 10.2. Thirty-three SNPs on SSC12 and 3 SNPs on SSC2 showed significant association with REMA at the last rib at the chromosome-wide significance level. None of the SNPs of REMA at the 5th–6th rib and only a few numbers of the SNPs of REMA at the 10th–11th ribs were found in this study. The Haploview V3.31 program and the Haplo.Stats R package were used to detect and visualize haplotype blocks and to analyze the association of the detected haplotype blocks with REMA at the last rib. A linkage analysis revealed that 4 haplotype blocks contained 4, 4, 2, and 4 SNPs, respectively. Annotations from pig reference genome suggested 2 genes（NOS2, NLK） in block 1（266 kb）, one gene（TMIGD1） in block 2（348 kb）, and one gene（MAP2K4） in block 3（453 kb）. A functional analysis indicated that MYH3 and MYH13 genes are the potential genes controlling REMA at the last rib. We screened several candidate intervals and genes based on the SNPs location and the gene function, and inferred that NOS2 and NLK genes maybe the main genes of REMA at the last ribs.展开更多
In the past few years, genome-wide association study （GWAS） has made great successes in identifying genetic susceptibility loci underlying many complex diseases and traits. The findings provide important genetic ins...In the past few years, genome-wide association study （GWAS） has made great successes in identifying genetic susceptibility loci underlying many complex diseases and traits. The findings provide important genetic insights into understanding pathogenesis of diseases. In this paper, we present an overview of widely used approaches and strategies for analysis of GWAS, offered a general consideration to deal with GWAS data. The issues regarding data quality control, population structure, association analysis, multiple comparison and visual presentation of GWAS results are discussed; other advanced topics including the issue of missing heritability, meta-analysis, setbased association analysis, copy number variation analysis and GWAS cohort analysis are also briefly introduced.展开更多
This paper presents a quick, easy to implement and versatile way of using stochastic simulations to investigate the power and design of using single nucleotide polymorphism (SNP) arrays for genome-wide association stu...This paper presents a quick, easy to implement and versatile way of using stochastic simulations to investigate the power and design of using single nucleotide polymorphism (SNP) arrays for genome-wide association studies in farm animals. It illustrates the methodology by discussing a small example where 6 experimental designs are considered to analyse the same resource consisting of 6006 animals with pedigree and phenotypic records: (1) genotyping the 30 most widely used sires in the population and all of their progeny (515 animals in total), (2) genotyping the 100 most widely used sires in the population and all of their progeny (1102 animals in total), genotyping respectively (3) 515 and (4) 1102 animals selected randomly or genotyping respectively (5) 515 and (6) 1102 animals from the tails of the phenotypic distribution. Given the resource at hand, designs where the extreme animals are genotyped perform the best, followed by designs selecting animals at random. Designs where sires and their progeny are genotyped perform the worst, as even genotyping the 100 most widely used sires and their progeny is not as powerful of genotyping 515 extreme animals.展开更多
Increasing the planting density is one way to enhance grain production in maize.However,high planting density brings about growth and developmental defects such as barrenness,which is the major factor limiting grain y...Increasing the planting density is one way to enhance grain production in maize.However,high planting density brings about growth and developmental defects such as barrenness,which is the major factor limiting grain yield.In this study,the barrenness was characterized in an association panel comprising 280 inbred lines under normal(67500 plants ha–1,ND)and high(120000 plants ha–1,HD)planting densities in 2017 and 2018.The population was genotyped using 776254 single nucleotide polymorphism(SNP)markers with criteria of minor allele frequency>5%and<20%missing data.A genome-wide association study(GWAS)was conducted for barrenness under ND and HD,as well as the barrenness ratio(HD/ND),by applying a Mixed Linear Model that controls both population structure and relative kinship(Q+K).In total,20 SNPs located in nine genes were significantly(P<6.44×10–8)associated with barrenness under the different planting densities.Among them,seven SNPs for barrenness at ND and HD were located in two genes,four of which were common under both ND and HD.In addition,13 SNPs for the barrenness ratio were located in seven genes.A complementary pathway analysis indicated that the metabolic pathways of amino acids,such as glutamate and arginine,and the mitogen-activated protein kinase(MAPK)signaling pathway might play important roles in tolerance to high planting density.These results provide insights into the genetic basis of high planting density tolerance and will facilitate high yield maize breeding.展开更多
OBJECTIVE Genetic variants in the pharmacokinetic(PK)mechanism are the main underlying factors that modify the antiplatelet efficacy of clopidogrel.Hence,joint analysis of genetic variants that modify pharmacodynamic(...OBJECTIVE Genetic variants in the pharmacokinetic(PK)mechanism are the main underlying factors that modify the antiplatelet efficacy of clopidogrel.Hence,joint analysis of genetic variants that modify pharmacodynamic(PD)and PK responses to clopidogrel should be effective for identifying the genetic variants affecting the antiplatelet response to the drug.METHODS A genome-wide association study was conducted to identify new genetic loci that modify PD responses to clopidogrel and its active metabolite H4 in 115 Chinese patients with coronary heart disease(CHD).RESULTS We identified novel variants in two transporter genes(rs12456693 in SLC14A2 and rs2487032 in ABCA1)and in N6AMT1(rs2254638)associated with clopidogrel-treated P2Y12reaction unit(PRU)and plasma H4 concentration.The associations between these single nucleotide polymorphisms(SNPs)and PK parameters of clopidogrel and H4 were observed in 31 additional CHD patients(P<0.05).The new variants,together with CYP2C19*2 and clinical factors,dramatically improved the predictability of PRU variability to 37.7%compared with the published value of approximately 20%.The function of these SNPs on the activation of clopidogrel was validated in 32 liver S9 fractions,and the N6AMT1 rs2254638 T variant was found to be associated with decreased formation of H4(P=0.0386).Meanwhile,N6AMT1 rs2254638 was further identified to exert a marginal risk effect for MACE in an independent CHD patient cohort(OR:1.428,95%CI:0.978-2.086,P=0.0653,FDR=0.4726).In conclusion,we systematically identified new genetic variants as risk factors for the reduced efficacy of clopidogrel.CONCLUSION Our study findings enhanced the understanding of the absorption and metabolic mechanisms that influence PD responses to clopidogrel treatment.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.32000377,32172037,and 32472211)the Biological Breeding-National Science and Technology Major Project,China(Grant No.2023ZD04068)+2 种基金the Fundamental Research Funds for the Central Universities,China(Grant No.KJQN202103)the open funds of the State Key Laboratory of Crop Genetics&Germplasm Enhancement and Utilization,China(Grant No.ZW202401)the Cyrus Tang Innovation Center for Crop Seed Industry,China.
文摘Rice grain yield is primarily determined by three key agronomic traits:panicle number,grain number per panicle,and grain weight(GW).However,the inherent tradeoffs among these yield components remain a persistent challenge in rice breeding programs.Notably,compared with GW,brown rice weight(BRW)provides a more direct metric associated with actual grain yield potential.In this study,we conducted a two-year replicated genome-wide association study to elucidate the genetic architecture of BRW and identify new loci regulating GW.Among seven consistently detected loci across experimental replicates,four were not co-localized with previously reported genes associated with BRW or GW traits.BRW1.1,one of the four newly identified loci,was found to encode a novel RNA-binding protein.Functional characterization revealed that BRW1.1 acts as a negative regulator of BRW,potentially through modulating mRNA translation processes.Intriguingly,through integrated analysis of mutant phenotypes and haplotype variations,we demonstrated that BRW1.1 mediates the physiological tradeoff between GW and panicle number.This study not only delineates the genetic determinants of BRW but also identifies BRW1.1 as a promising molecular target for breaking the yield component tradeoff in precision rice breeding.
基金supported by grants from the Basic Research Business Fees for Public Welfare in Xinjiang Autonomous Region(Mining candidate genes related to grape seed traits based on GWAS,KY2023028)the Xinjiang Uygur Autonomous Region Tianchi Talent-Young Doctor for Chuan Zhang(Revealing the domestication history of Xinjiang native grape varieties and genetic analysis of important agronomic traits)the Xinjiang Academy of Agricultural Sciences Youth Science and Technology Backbone Innovation Ability Training Project(xjnkq-2023006).
文摘Seedlessness has always been a valuable quality characteristic of edible grape varieties.Although the production of seedless grapes has been ongoing for decades,the genetic complexity of seedless grapes is not yet fully understood.Therefore,determining the genetic mechanisms and key regulatory genes of seedless grapes is of great significance for seedless grape breeding and meeting market demands.The emergence of high-throughput analysis software offers greater possibilities for mining genes related to plant organ development.Specifically,to mine a greater number of candidate genes related to grape seed traits,this study used the seed trait parameters analyzed by Tomato Analyzer as the target trait and then used a genome-wide association study(GWAS)to mine candidate genes.In the two-year analysis using principal component analysis(PCA),we extracted five principal components with a cumulative contribution rate of 96.586%.The cumulative contribution rate for component 1 reached 87.352%.Correlation analysis revealed correlation coefficients ranging from 0.54 to 0.98 among the seven basic traits.The GWAS results indicated that 370 SNP loci were significantly correlated with seed traits.These SNP loci were distributed on 18 chromosomes,except for chromosome 4,with most SNP loci distributed on chromosome 18.Based on the physical location of single nucleotide polymorphism(SNP)markers significantly associated with seed-related traits in the grape reference genome,candidate genes are screened within the range of linkage disequilibrium(LD)attenuation distance,both upstream and downstream of the significant SNP loci.These candidate genes were mainly transcription factor-related genes(VvMADS4 and VvMADS5),ubiquitin ligase-related genes(E3 ubiquitin ligase BIG BROTHER),serine/threonine protein kinase-related genes,and carbohydrate metabolism-related genes(Sucrose Synthase 2)and simultaneously controlled multiple(at least two or more)seed traits.These results indicate that seed traits are jointly regulated by some genes involved in seed morphology regulation.In this work,we identified new gene loci related to grape seed traits.Identifying molecular markers closely related to these seed traits is of great significance for breeding seedless grape varieties.
基金supported by the Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City,China(Grant No.2021JJLH0041)the Zhejiang Provincial Natural Science Foundation,China(Grant No.LY23C130006)+3 种基金the National Natural Science Foundation of China(Grant No.32472207)Nanfan Special Project,Chinese Academy of Agricultural Sciences(Grant Nos.YBXM2436 and YBXM2326)the Hainan Province Science and Technology Special Fund,China(Grant No.ZDYF2022XDNY256)the Innovational Fund for Scientific and Technological Personnel of Hainan Province,China(Grant No.KJRC2023B24).
文摘The genetic mechanism determining amylose content(AC)and its impact on eating and cooking quality(ECQ)of rice is highly complex.To elucidate the genetic basis of AC in rice,the Ting’s core collection was used to identify novel AC genes/loci through genome-wide association analysis(GWAS)using more than 5.0 million single nucleotide polymorphisms(SNPs).In this study,12 genes related to AC,including the major gene Wx and 11 minor genes,were detected using the EMMAX method.A novel gene,LR,encoding a nucleotide-binding leucine-rich-repeat(LRR)receptor(NLR)family protein,was selected for functional study.When LR was knocked out using CRISPR/Cas9,the AC decreased significantly.Furthermore,the AC in varieties was significantly higher with Haplotype A compared to Haplotypes B and C of LR.Notably,two natural variations,SNP-385(Thr-Hap.A vs Ala-Haps.B and C)and SNP-758(Ser-Hap.A vs Asn-Haps.B and C),in the coding region of LR might play critical roles in regulating AC and serve as potential targets for cultivating rice with diverse amylose contents.
基金supported by the Shenzhen Science and Technology Program,China(Grant No.KCXFZ20211020163808012)the Nanfan Special Project,Chinese Academy of Agricultural Sciences,China(Grant No.YBXM2426).
文摘Alkaline soil is characterized by high soluble salt content,elevated pH levels,and ionic imbalance,all of which collectively intensify the harmful effects of alkaline stress on plants.To gain molecular insights into alkaline tolerance(AT),we evaluated 13 AT-related traits in 508 diverse rice accessions from the 3K Rice Germplasm Project at the seedling stage.A total of 2929764,2059114,and 1365868 single nucleotide polymorphisms were used to identify alkaline-tolerance QTLs via genome-wide association studies(GWAS)in the entire population as well as in the xian and geng subpopulations,respectively.Candidate genes and their superior haplotypes were further identified through gene-based association,haplotype analysis,and gene function annotation.In total,99 QTLs were identified for AT by GWAS,and three genes(LOC_Os03g49050 for qSSD3.1,LOC_Os05g48760 for qSKC5,and LOC_Os12g01922 for qSNC12)were selected as the most promising candidate genes.Furthermore,we successfully mined superior alleles of key candidate genes from natural variants associated with AT-related traits.This study identified crucial candidate genes and their favorable alleles for AT traits,laying a foundation for further gene cloning and the development of AT rice varieties via marker-assisted selection.
基金supported by the National Key R&D Program of China(2022YFD1201802)the Shandong Key R&D Program,China(2022CXGC010607)+2 种基金the Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences(CAAS-ZDRW202109)the Agricultural Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences(CAAS-ASTIP2017-ICS)the Subproject of the Major Project of Science and Technology in Shanxi Province,China(202201140601025-1-02)。
文摘Southern corn rust(SCR)is an airborne fungal disease caused by Puccinia polysora Underw.(P.polysora)that adversely impacts maize quality and yields worldwide.Screening for new elite SCR-resistant maize loci or genes has the potential to enhance overall resistance to this pathogen.Using phenotypic SCR resistance-related data collected over two years and three geographical environments,a genome-wide association study was carried out in this work,which eventually identified 91 loci that were substantially correlated with SCR susceptibility.These included 13 loci that were significant in at least three environments and overlapped with 74 candidate genes(B73_RefGen_v4).Comparative transcriptomic analyses were then performed to identify the genes related to SCR infection,with 2,586 and 797 differentially expressed genes(DEGs)ultimately being identified in the resistant Qi319and susceptible 8112 inbred lines following P.polysora infection,respectively,including 306 genes common to both lines.Subsequent integrative multi-omics investigations identified four potential candidate SCR response-related genes.One of these genes is ZmHCT9,which encodes the protein hydroxycinnamoyl transferase 9.This gene was up-regulated in susceptible inbred lines and linked to greater P.polysora resistance as confirmed through cucumber mosaic virus(CMV)-based virus induced-gene silencing(VIGS)system-mediated gene silencing.These data provide important insights into the genetic basis of the maize SCR response.They will be useful for for future research on potential genes related to SCR resistance in maize.
基金financially supported by the National Natural Science Foundation of China(Grant No.U20A2032)the Agro ST Project(Grant No.NK2022050102)the Hainan Provincial Natural Science Foundation,China(Grant No.323MS066)。
文摘Rice cooking and eating qualities(CEQ)are mainly determined by cooked rice textural parameters and starch physicochemical properties.However,the genetic bases of grain texture and starch properties in rice have not been fully understood.We conducted a genome-wide association study for apparent amylose content(AAC),starch pasting viscosities,and cooked rice textural parameters using 279 indica rice accessions from the 3000 Rice Genome Project.We identified 26 QTLs in the whole population and detected single nucleotide polymorphisms(SNPs)with the lowest P-value at the Waxy(Wx)locus for all traits except pasting temperature and cohesiveness.Additionally,we detected significant SNPs at the SUBSTANDARD STARCH GRAIN6(SSG6)locus for AAC,setback(SB),hardness,adhesiveness,chewiness(CHEW),gumminess(GUM),and resilience.We subsequently divided the population using a SNP adjacent to the Waxy locus,and identified 23 QTLs and 12 QTLs in two sub-panels,WxT and WxA,respectively.In these sub-panels,SSG6 was also identified to be associated with pasting parameters,including peak viscosity,hot paste viscosity,cold paste viscosity,and consistency viscosity.Furthermore,a candidate gene encoding monosaccharide transporter 5(OsMST5)was identified to be associated with AAC,breakdown,SB,CHEW,and GUM.In total,39 QTLs were co-localized with known genes or previously reported QTLs.These identified genes and QTLs provide valuable information for genetic manipulation to improve rice CEQ.
基金This work was supported by the National Key Research and Development Program of China(2022YFD1200201)Henan Provincial Science and Technology Research and Development Plan Joint Fund(222301420025)the Agricultural Science and Technology Innovation Program(ASTIP)of CAAS.
文摘Nitrogen(N)fertilizer application is essential for crop-plant growth and development.Identifying genetic loci associated with N-use efficiency(NUE)could increase wheat yields and reduce environmental pollution caused by overfertilization.We subjected a panel of 389 wheat accessions to N and chlorate(a nitrate analog)treatments to identify quantitative trait loci(QTL)controlling NUE-associated traits at the wheat seedling stage.Genotyping the panel with a 660K single-nucleotide polymorphism(SNP)array,we identified 397 SNPs associated with N-sensitivity index and chlorate inhibition rate.These SNPs were merged into 49 QTL,of which eight were multi-environment stable QTL and 27 were located near previously reported QTL.A set of 135 candidate genes near the 49 QTL included TaBOX(F-box family protein)and TaERF(ethylene-responsive transcription factor).A Tabox mutant was more sensitive to low-N stress than the wild-type plant.We developed two functional markers for Hap 1,the favorable allele of TaBOX.
基金funded by the National Key Research and Development Program of China (2016YFD0100301)Project for Cultivating New Transgenic Varieties (2016ZX08009003-004)+2 种基金the Agricultural Science and Technology Innovation Program and the Cooperation and Innovation Mission (CAAS-ZDXT202001)Open Fund of Hubei Collaborative Innovation Center for Grain Industry (HCICGI2020-06)the National Natural Science Foundation of China (U19A2025 and 31870229)。
文摘Appearance and cooked rice elongation are key quality traits of rice. Although some QTL for these traits have been identified, understanding of the genetic relationship between them remains limited. In the present study, large phenotypic variation was observed in 760 accessions from the 3 K Rice Genomes Project for both appearance quality and cooked rice elongation. Most component traits of appearance quality and cooked rice elongation showed significant pairwise correlations, but a low correlation was found between appearance quality and cooked rice elongation. A genome-wide association study identified 74 QTL distributed on all 12 chromosomes for grain length, grain width, length to width ratio, degree of endosperm with chalkiness, rice elongation difference, and elongation index. Thirteen regions containing QTL stably expressed in multiple environments and/or exerting pleiotropic effects on multiple traits were detected. By gene-based association analysis and haplotype analysis, 46 candidate genes, including five cloned genes, and 49 favorable alleles were identified for these 13 QTL. The effect of the candidate gene Wx on rice elongation difference was validated by a transgenic strategy. These results shed light on the genetic bases of appearance quality and cooked rice elongation and provide gene resources for improving rice quality by molecular breeding.
基金supported by the Agricultural Science and Technology Innovation Program, China (ASTIPIAS02)the National Key Technology R&D Program of China (2011BAD28B01)+2 种基金the National Natural Science Foundation of China (31201781)the Earmarked Fund for Modern Agroindustry Technology Research System, National Technology Program of China (2011ZX08006-003)the Chinese Academy of Agricultural Sciences Foundation (2011cj-5, 2012ZL069 and 2014ywf-yb-8)
文摘Porcine carcass traits and organ weights have important economic roles in the swine industry. A total of 576 animals from a Large White×Minzhu intercross population were genotyped using the Illumina PorcineSNP60K Beadchip and were phenotyped for 10 traits, speciifcally, backfat thickness （6-7 libs）, carcass length, carcass weight, foot weight, head weight, heart weight, leaf fat weight, liver weight, lung weight and slaughter body weight. The genome-wide association study （GWAS） was assessed by Genome Wide Rapid Association using the mixed model and regression-genomic control approach. A total of 31 single nucleotide polymorphisms （SNPs） （with the most signiifcant SNP being MARC0033464, P value=6.80×10-13） were located in a 9.76-Mb （31.24-41.00 Mb） region on SSC7 and were found to be signiifcantly associated with one or more carcass traits and organ weights. High percentage of phenotypic variance explanation was observed for each trait ranging from 31.21 to 67.42%. Linkage analysis revealed one haplotype block of 495 kb, in which the most signiifcant SNP being MARC0033464 was contained, on SSC7 at complete linkage disequilibrium. Annotation of the pig reference genome suggested 6 genes （GRM4, HMGA1, NUDT3, RPS10, SPDEF and PACSIN1） in this candidate linkage disequilibrium （LD） interval. Functional analysis indicated that the HMGA1 gene presents the prime biological candidate for carcass traits and organ weights in pig, with potential application in breeding programs.
基金The authors gratefully acknowledge the financial support from the MasAgro project funded by Mexico’s Secretary of Agriculture and Rural Development(SADER),the Genomic Open-source Breeding Informatics Initiative(GOBII)(grant number OPP1093167)supported by the Bill&Melinda Gates Foundation,and the CGIAR Research Program(CRP)on maize(MAIZE)MAIZE receives W1&W2 support from the Governments of Australia,Belgium,Canada,China,France,India,Japan,the Republic of Korea,Mexico,Netherlands,New Zealand,Norway,Sweden,Switzerland,the United Kingdom,USA,and the World Bank+2 种基金The authors also thank the National Natural Science Foundation of China(grant number 31801442)the CIMMYT–China Specialty Maize Research Center Project funded by the Shanghai Municipal Finance Bureauthe China Scholarship Council.
文摘Fusarium ear rot(FER)is a destructive maize fungal disease worldwide.In this study,three tropical maize populations consisting of 874 inbred lines were used to perform genomewide association study(GWAS)and genomic prediction(GP)analyses of FER resistance.Broad phenotypic variation and high heritability for FER were observed,although it was highly influenced by large genotype-by-environment interactions.In the 874 inbred lines,GWAS with general linear model(GLM)identified 3034 single-nucleotide polymorphisms(SNPs)significantly associated with FER resistance at the P-value threshold of 1×10^(-5),the average phenotypic variation explained(PVE)by these associations was 3%with a range from 2.33%to 6.92%,and 49 of these associations had PVE values greater than 5%.The GWAS analysis with mixed linear model(MLM)identified 19 significantly associated SNPs at the P-value threshold of 1×10^(-4),the average PVE of these associations was 1.60%with a range from 1.39%to 2.04%.Within each of the three populations,the number of significantly associated SNPs identified by GLM and MLM ranged from 25 to 41,and from 5 to 22,respectively.Overlapping SNP associations across populations were rare.A few stable genomic regions conferring FER resistance were identified,which located in bins 3.04/05,7.02/04,9.00/01,9.04,9.06/07,and 10.03/04.The genomic regions in bins 9.00/01 and 9.04 are new.GP produced moderate accuracies with genome-wide markers,and relatively high accuracies with SNP associations detected from GWAS.Moderate prediction accuracies were observed when the training and validation sets were closely related.These results implied that FER resistance in maize is controlled by minor QTL with small effects,and highly influenced by the genetic background of the populations studied.Genomic selection(GS)by incorporating SNP associations detected from GWAS is a promising tool for improving FER resistance in maize.
基金funded by the Max-Planck-Gesellschaft Partner Group Grant(K.T.)the National Natural Science Foundation of China(31371267,31322030,and 91331108,K.T.+10 种基金91631307,S.W.30890034,31271338,L.J.and 31525014,91731303,31771388,31961130380,and 32041008,S.X.)supported by the National Basic Research Program(2015FY111700,L.J.)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01,L.J.,S.X.,and S.W.)the Ministry of Education(311016,L.J.)Strategic Priority Research Program of the Chinese Academy of Sciences(CAS)(XDB13040000,S.X.and S.W.)the UK Royal Society-Newton Advanced Fellowship(NAFn R1n191094)Key Research Program of Frontier Sciences(QYZDJ-SSW-SYS009)of the Chinese Academy of Sciencesthe support of a National Thousand Young Talents Award and a Max Planck-CAS Paul Gerson Unna Independent Research Group Leadership Award(S.W.)the Science and Technology Commission of Shanghai Municipality(16JC1400504,S.W.)。
文摘The human face is a heritable surface with many complex sensory organs.In recent years,many genetic loci associated with facial features have been reported in different populations,yet there is a lack of studies on the Han Chinese population.Here,we report a genome-wide association study of 3D normal human faces of 2,659 Han Chinese with autosegment phenotypes of facial morphology.We identify singlenucleotide polymorphisms(SNPs)encompassing four genomic regions showing significant associations with different facial regions,including SNPs in DENND1 B associated with the chin,SNPs among PISRT1 associated with eyes,SNPs between DCHS2 and SFRP2 associated with the nose,and SNPs in VPS13 B associated with the nose.We replicate 24 SNPs from previously reported genetic loci in different populations,whose candidate genes are DCHS2,SUPT3 H,HOXD1,SOX9,PAX3,and EDAR.These results provide a more comprehensive understanding of the genetic basis of variation in human facial morphology.
基金supported by the National Natural Science Foundation of China(Grant Nos.31271297 and 31222042) "One-hundred talents" Startup Funds from Chinese Academy of SciencesNational Key Basic Research Program(No. 2009CB 118402)
文摘Increasing yield is one of the most important goals in crop breeding. Soybean （Glycine max L. Merr.）, one of the most economically important leguminous seed crops, provides the majority of plant proteins, and more than a quarter of the world＇s food and animal feed （Graham and Vance, 2003）. The yield of soybean is finally determined by the number of seeds per unit area, which affected by many characters, such as height, branching number, photosynthesis, seed size, seed number. The number of seeds per pod is taken for one of the critical components that related to yield （You et al., 1995）.
基金supported by the National Natural Science Foundation of China (31971936)the Science &Technology Projects of Shandong Province, China (2019YQ028, 2020CXGC010805, 2019B08, 2019YQ014 and ZR2020MC093)
文摘Wheat grain yield is generally sink-limited during grain filling.The grain-filling rate(GFR)plays a vital role but is poorly studied due to the difficulty of phenotype surveys.This study explored the grain-filling traits in a recombinant inbred population and wheat collection using two highly saturated genetic maps for linkage analysis and genome-wide association study(GWAS).Seventeen stable additive quantitative trait loci(QTLs)were identified on chromosomes 1B,4B,and 5A.The linkage interval between IWB19555 and IWB56078 showed pleiotropic effects on GFR_(1),GFR_(max),kernel length(KL),kernel width(KW),kernel thickness(KT),and thousand kernel weight(TKW),with the phenotypic variation explained(PVE)ranging from 13.38%(KW)to 33.69%(TKW).198 significant marker-trait associations(MTAs)were distributed across most chromosomes except for 3D and 4D.The major associated sites for GFR included IWB44469(11.27%),IWB8156(12.56%)and IWB24812(14.46%).Linkage analysis suggested that IWB35850,identified through GWAS,was located in approximately the same region as QGFR_(max)2B.3-11,where two high-confidence candidate genes were present.Two important grain weight(GW)-related QTLs colocalized with grain-filling QTLs.The findings contribute to understanding the genetic architecture of the GFR and provide a basic approach to predict candidate genes for grain yield trait QTLs.
基金founded by the National Natural Science Foundation of China(81202283,81473070,81373102 and81202267)Key Grant of Natural Science Foundation of the Jiangsu Higher Education Institutions of China(10KJA330034 and11KJA330001)+1 种基金the Research Fund for the Doctoral Program of Higher Education of China(20113234110002)the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine)
文摘With recent advances in biotechnology, genome-wide association study （GWAS） has been widely used to identify genetic variants that underlie human complex diseases and traits. In case-control GWAS, typical statistical strategy is traditional logistical regression （LR） based on single-locus analysis. However, such a single-locus analysis leads to the well-known multiplicity problem, with a risk of inflating type I error and reducing power. Dimension reduction-based techniques, such as principal component-based logistic regression （PC-LR）, partial least squares-based logistic regression （PLS-LR）, have recently gained much attention in the analysis of high dimensional genomic data. However, the perfor- mance of these methods is still not clear, especially in GWAS. We conducted simulations and real data application to compare the type I error and power of PC-LR, PLS-LR and LR applicable to GWAS within a defined single nucleotide polymorphism （SNP） set region. We found that PC-LR and PLS can reasonably control type I error under null hypothesis. On contrast, LR, which is corrected by Bonferroni method, was more conserved in all simulation settings. In particular, we found that PC-LR and PLS-LR had comparable power and they both outperformed LR, especially when the causal SNP was in high linkage disequilibrium with genotyped ones and with a small effective size in simulation. Based on SNP set analysis, we applied all three methods to analyze non-small cell lung cancer GWAS data.
基金supported jointly by Cariplo(Italia)and Agropolis(France)Foundations(Grant No.1201-006).
文摘Genome-wide association study(GWAS)was performed for 16 agronomic traits including nitrogen use efficiency(NUE)and yield-related components using a panel of 190 mainly japonica rice varieties and a set of 38390 single nucleotide polymorphism(SNP)markers.This panel was evaluated under rainfed upland conditions in Madagascar in two consecutive cropping seasons with two contrasted nitrogen input levels.Using another set of five grain traits,we identified previously known genes(GW5,GS3,Awn1 and Glabrous1),thus validating the pertinence and accuracy of our datasets for GWAS.A total of 369 significant associations were detected between SNPs and agronomic traits,gathered into 46 distinct haplotype groups and 28 isolated markers.Few association signals were identified for the complex quantitative trait NUE,however,larger number of quantitative trait loci(QTLs)were detected for its component traits,with 10 and 2 association signals for nitrogen utilization efficiency and nitrogen uptake efficiency,respectively.Several detected association signals co-localized with genes involved in nitrogen transport or nitrogen remobilization within 100 kb.The present study thus confirmed the potential of GWAS to identify candidate genes and new loci associated with agronomic traits.However,because of the quantitative and complex nature of NUE-related traits,GWAS might have not captured a large number of QTLs with limited effects.
基金supported by the Agricultural Science and Technology Innovation Program,China(ASTIP-IAS02)the National Key Technology R&D Program of China(2011BAD28B01)+3 种基金the National Natural Science Foundation of China(31201781)the National High Technology Re-search and Development Program of China(2011ZX08006-003)the Earmarked Fund for Modern Agro-industry Technology Research System of ChinaChinese Academy of Agricultural Sciences Foundation(2011cj-5)
文摘Rib eye muscle area（REMA） is an economically important trait and one of the main selection criteria for breeding in the swine industry. In the genome-wide association study（GWAS）, the Illumina Porcine SNP60 Bead Chip containing 62 163 single nucleotide polymorphisms（SNPs） was used to genotype 557 pigs from a porcine Large White×Minzhu intercross population. The REMA（at the 5th–6th, 10th–11th and the last ribs） was measured after slaughtered at the age of（240±7） d for each animal. Association tests between REMA trait and SNPs were performed via the Genome-Wide Rapid Association using the Mixed Model and Regression-Genomic Control（GRAMMAR-GC） approach. From the Ensembl porcine database, SNP annotation was implemented using Sus scrofa Build 10.2. Thirty-three SNPs on SSC12 and 3 SNPs on SSC2 showed significant association with REMA at the last rib at the chromosome-wide significance level. None of the SNPs of REMA at the 5th–6th rib and only a few numbers of the SNPs of REMA at the 10th–11th ribs were found in this study. The Haploview V3.31 program and the Haplo.Stats R package were used to detect and visualize haplotype blocks and to analyze the association of the detected haplotype blocks with REMA at the last rib. A linkage analysis revealed that 4 haplotype blocks contained 4, 4, 2, and 4 SNPs, respectively. Annotations from pig reference genome suggested 2 genes（NOS2, NLK） in block 1（266 kb）, one gene（TMIGD1） in block 2（348 kb）, and one gene（MAP2K4） in block 3（453 kb）. A functional analysis indicated that MYH3 and MYH13 genes are the potential genes controlling REMA at the last rib. We screened several candidate intervals and genes based on the SNPs location and the gene function, and inferred that NOS2 and NLK genes maybe the main genes of REMA at the last ribs.
基金supported by National Natural Science Foundation of China(No.81072389,81373102,81473070 and 81402765)Research Found for the Doctoral Program of Higher Education of China(No.20113234110002)+4 种基金Key Grant of Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.10KJA330034)College Philosophy and Social Science Foundation from Education Department of Jiangsu Province of China(No.2013SJB790059,2013SJD790032)Research Foundation from Xuzhou Medical College(No.2012KJ02)Research and Innovation Project for College Graduates of Jiangsu Province of China(No.CXLX13_574)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘In the past few years, genome-wide association study （GWAS） has made great successes in identifying genetic susceptibility loci underlying many complex diseases and traits. The findings provide important genetic insights into understanding pathogenesis of diseases. In this paper, we present an overview of widely used approaches and strategies for analysis of GWAS, offered a general consideration to deal with GWAS data. The issues regarding data quality control, population structure, association analysis, multiple comparison and visual presentation of GWAS results are discussed; other advanced topics including the issue of missing heritability, meta-analysis, setbased association analysis, copy number variation analysis and GWAS cohort analysis are also briefly introduced.
基金Project supported by Ovita Limited, Dunedin, New Zealand
文摘This paper presents a quick, easy to implement and versatile way of using stochastic simulations to investigate the power and design of using single nucleotide polymorphism (SNP) arrays for genome-wide association studies in farm animals. It illustrates the methodology by discussing a small example where 6 experimental designs are considered to analyse the same resource consisting of 6006 animals with pedigree and phenotypic records: (1) genotyping the 30 most widely used sires in the population and all of their progeny (515 animals in total), (2) genotyping the 100 most widely used sires in the population and all of their progeny (1102 animals in total), genotyping respectively (3) 515 and (4) 1102 animals selected randomly or genotyping respectively (5) 515 and (6) 1102 animals from the tails of the phenotypic distribution. Given the resource at hand, designs where the extreme animals are genotyped perform the best, followed by designs selecting animals at random. Designs where sires and their progeny are genotyped perform the worst, as even genotyping the 100 most widely used sires and their progeny is not as powerful of genotyping 515 extreme animals.
基金the 2020 Research Program of Sanya Yazhou Bay Science and Technology City,China(SKJC-2020-02-005)the Agricultural Science and Technology Innovation Program(ASTIP)of Chinese Academy of Agricultural Sciences(CAAS-ZDRW202004 and CAAS-ZDRW202109).
文摘Increasing the planting density is one way to enhance grain production in maize.However,high planting density brings about growth and developmental defects such as barrenness,which is the major factor limiting grain yield.In this study,the barrenness was characterized in an association panel comprising 280 inbred lines under normal(67500 plants ha–1,ND)and high(120000 plants ha–1,HD)planting densities in 2017 and 2018.The population was genotyped using 776254 single nucleotide polymorphism(SNP)markers with criteria of minor allele frequency>5%and<20%missing data.A genome-wide association study(GWAS)was conducted for barrenness under ND and HD,as well as the barrenness ratio(HD/ND),by applying a Mixed Linear Model that controls both population structure and relative kinship(Q+K).In total,20 SNPs located in nine genes were significantly(P<6.44×10–8)associated with barrenness under the different planting densities.Among them,seven SNPs for barrenness at ND and HD were located in two genes,four of which were common under both ND and HD.In addition,13 SNPs for the barrenness ratio were located in seven genes.A complementary pathway analysis indicated that the metabolic pathways of amino acids,such as glutamate and arginine,and the mitogen-activated protein kinase(MAPK)signaling pathway might play important roles in tolerance to high planting density.These results provide insights into the genetic basis of high planting density tolerance and will facilitate high yield maize breeding.
基金The project supported by National Natural Science Foundation of China(81373486)Science and Technology Development Projects of Guangdong Province,China(2016B090918114,2013B021800157)Science and Technology Development Projects of Guangzhou,Guangdong,China(201510010236,201604020096)
文摘OBJECTIVE Genetic variants in the pharmacokinetic(PK)mechanism are the main underlying factors that modify the antiplatelet efficacy of clopidogrel.Hence,joint analysis of genetic variants that modify pharmacodynamic(PD)and PK responses to clopidogrel should be effective for identifying the genetic variants affecting the antiplatelet response to the drug.METHODS A genome-wide association study was conducted to identify new genetic loci that modify PD responses to clopidogrel and its active metabolite H4 in 115 Chinese patients with coronary heart disease(CHD).RESULTS We identified novel variants in two transporter genes(rs12456693 in SLC14A2 and rs2487032 in ABCA1)and in N6AMT1(rs2254638)associated with clopidogrel-treated P2Y12reaction unit(PRU)and plasma H4 concentration.The associations between these single nucleotide polymorphisms(SNPs)and PK parameters of clopidogrel and H4 were observed in 31 additional CHD patients(P<0.05).The new variants,together with CYP2C19*2 and clinical factors,dramatically improved the predictability of PRU variability to 37.7%compared with the published value of approximately 20%.The function of these SNPs on the activation of clopidogrel was validated in 32 liver S9 fractions,and the N6AMT1 rs2254638 T variant was found to be associated with decreased formation of H4(P=0.0386).Meanwhile,N6AMT1 rs2254638 was further identified to exert a marginal risk effect for MACE in an independent CHD patient cohort(OR:1.428,95%CI:0.978-2.086,P=0.0653,FDR=0.4726).In conclusion,we systematically identified new genetic variants as risk factors for the reduced efficacy of clopidogrel.CONCLUSION Our study findings enhanced the understanding of the absorption and metabolic mechanisms that influence PD responses to clopidogrel treatment.
