Epistasis-aware genome-wide association studies provide insights into the efficient breeding of high-yield and high-quality rice

Marker-assisted selection(MAS)and genomic selection(GS)breeding have greatly improved the efficiency of rice breeding.Due to the influences of epistasis and gene pleiotropy,ensuring the actual breeding effect of MAS and GS is still a difficult challenge to overcome.In this study,113 indica rice varieties(V)and their 565 testcross hybrids(TC)were used as the materials to investigate the genetic basis of 12 quality traits and nine agronomic traits.The original traits and general combining ability of the parents,as well as the original traits and midparent heterosis of TC,were subjected to genome-wide association analysis.In total,381 primary significantly associated loci(SAL)and 1,759 secondary SALs that had epistatic interactions with these primary SALs were detected.Among these loci,322 candidate genes located within or nearby the SALs were screened,204 of which were cloned genes.A total of 39 MAS molecular modules that are beneficial for trait improvement were identified by pyramiding the superior haplotypes of candidate genes and desirable epistatic alleles of the secondary SALs.All the SALs were used to construct genetic networks,in which 91 pleiotropic loci were investigated.Additionally,we estimated the accuracy of genomic prediction in the parent V and TC by incorporating either no SALs,primary SALs,secondary SALs or epistatic effect SALs as covariates.Although the prediction accuracies of the four models were generally not significantly different in the TC dataset,the incorporation of primary SALs,secondary SALs,and epistatic effect SALs significantly improved the prediction accuracies of 5(26%),3(16%),and 11(58%)traits in the V dataset,respectively.These results suggested that SALs and epistatic effect SALs identified based on an additive genotype can provide considerable predictive power for the parental lines.They also provide insights into the genetic basis of complex traits and valuable information for molecular breeding in rice.

Genome-wide association study of seedling nitrogen-use efficiency-associated traits in common wheat(Triticum aestivum L.)

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.

Genome-Wide Association Study of Cooked Rice Textural Attributes and Starch Physicochemical Properties in indica Rice

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.

Genome-wide and candidate gene association studies identify BnPAP17 as conferring the utilization of organic phosphorus in oilseed rape

Phosphorus(P)is essential for living plants,and P deficiency is one of the key factors limiting the yield in rapeseed production worldwide.As the most important organ for plants,root morphology traits(RMTs)play a key role in P absorption.To investigate the genetic variability of RMT under low P availability,we dissected the genetic structure of RMTs by genome-wide association studies(GWAS),linkage mapping and candidate gene association studies(CGAS).A total of 52 suggestive loci were associated with RMTs under P stress conditions in 405 oilseed rape accessions.The purple acid phosphatase gene BnPAP17 was found to control the lateral root number(LRN)and root dry weight(RDW)under low P stress.The expression of BnPAP17 was increased in shoot tissue in P-efficient cultivars compared to root tissue and P-inefficient cultivars in response to low P stress.Moreover,the haplotype of BnPAP17^(Hap3)was detected for the selective breeding of P efficiency in oilseed rape.Over-expression of the BnPAP17^(Hap3)could promote the shoot and root growth with enhanced tolerance to low P stress and organic phosphorus(Po)utilization in oilseed rape.Collectively,these findings increase our understanding of the mechanisms underlying BnPAP17-mediated low P stress tolerance in oilseed rape.

Association of eczema with risk of pan-cancers:a two-sample Mendelian randomization study

Background:Both eczema and tumor are associated with immune disorders.Although several investigations have observed the rela-tionship between eczema and certain cancers,evidence for causality is lacking.Methods:We conducted a two-sample Mendelian randomization(MR)study to examine and explore the genetic association between eczema and pan-cancers.Upon satisfying the three core assumptions of MR,we analyzed the causality between eczema and 15 site-specific cancers utilizing an inverse variance weighted method.We verified the results through a series of sensitivity and reverse direction analyses.The exposure and outcome datasets were substituted from the FinnGen and genome-wide association studies catalog data-bases.A meta-analysis on primary and validation analyses was performed to combine the estimates of MR study.Results:Based on the MR analysis results,eczema was associated with an increased risk of lung cancer(odds ratio[OR]=1.0427,95%confidence interval[CI]=1.0082–1.0783,P=0.0148)and brain cancer(OR=1.0285,95%CI=1.0120–1.0452,P=0.0007)and de-creased risk of colorectal cancer(OR=0.9324,95%CI=0.8774–0.9909,P=0.0242)and malignant neoplasm of the kidney(OR=0.9323,95%CI=0.8834–0.9839,P=0.0108).The sensitivity analysis indicated that the results were stable and reliable,and the reverse MR analyses demonstrated no causation between the cancers of interest and eczema.Conclusions:Our results identified eczema as a genetic risk factor for lung and brain cancer and a protective factor for colorectal cancer and malignant neoplasm of the kidney.No connection was observed between eczema and other cancers.Further evidence from epide-miological and mechanistic studies is needed to elucidate these findings in detail.

Genetic Parameters and Genome-Wide Association Studies for Body Size Traits of Shuxuan Cattle in China

In domestic cattle,the body size traits have important implications in terms of breed characteristics and production performance.Shuxuan cattle is a dual-purpose breed mainly raised in Sichuan province,China,for which we have known less about the genetic parameters and underlying candidate genes in relation to the body size traits.In this study,we obtained the genome-wide single nucleotide polymorphisms(SNPs)using the Illumina Bovine BeadChip in 275 Shuxuan cattle.These SNPs were first used for estimating genetic parameters for the withers height(WH)and diagonal body length(BL).Using the bivariate animal model,the estimates(±standard error)of heritabilities were 0.71±0.22 and 0.49±0.29 for BL,and their genetic correlation was 0.64±0.37.Second,the genome-wide association study(GWAS)was performed.However,these did not result into genome-wide significant SNPs for both WH and BL traits.According to a less stringent suggestive significance,some positional candidate genes were found,and some of them(such as FAM110B,TAS1R2,PAX3,and FHIT)were previously reported in literature to be associated with body size traits in cattle.In conclusion,we estimated the genetic parameters in Shuxuan cattle using genomic information for the first time,which are required for implementing the genomic selection programs in the future.

The Genetic Association between CDKN1A and Heart Failure:Genome-Wide Exploration of m6A-SNPs and Mendelian Randomization

Objective N6-methyladenosine(m^(6)A)is a common epigenetic modification in eukaryotes.In this study,we explore the potential impact of m^(6)A-associated single nucleotide polymorphisms(m^(6)A-SNPs)on heart failure(HF).Methods Data from genome-wide association studies(GWAS)investigating HF in humans and from m^(6)A-SNPs datasets were used to identify HF-associated m^(6)A-SNPs.Their functions were explored using expression quantitative trait locus(eQTL),gene expression,and gene enrichment analyses.Mediation protein quantitative trait locus(pQTL)-Mendelian randomization(MR)was used to investigate the potential mechanism between critical protein levels and risk factors for HF.Results We screened 44 HF-associated m^(6)A-SNPs,including 10 m^(6)A-SNPs that showed eQTL signals and differential expressions in HF.The SNP rs1801270 in CDKN1A showed the strongest association with HF(P=7.75×10^(−6)).Additionally,MR verified the genetic association between the CDKN1A protein and HF,as well as the mediating effect of blood pressure(BP)in this pathway.Higher circulating level of CDKN1A was associated with a lower risk of HF(odds ratio[OR]=0.82,95%confidence interval[CI]:0.69 to 0.99).The proportions of hypertension,systolic BP,and diastolic BP were 48.10%,28.94%,and 18.02%,respectively.Associations of PDIA6(P=1.30×10^(−2))and SMAD3(P=4.80×10^(−2))with HF were also detected.Conclusion Multiple HF-related m^(6)A-SNPs were identified in this study.Genetic associations of CDKN1A and other proteins with HF and its risk factors were demonstrated,providing new ideas for further exploration of the molecular mechanisms of HF.

Macrophage migration inhibitory factor gene polymorphisms in inflammatory bowel disease: An association study in New Zealand Caucasians and meta-analysis

AIM:To investigate the association of macrophage migration inhibitory factor(MIF)promoter polymorphisms with inflammatory bowel disease(IBD)risk.METHODS:One thousand and six New Zealand Caucasian cases and 540 Caucasian controls were genotyped for the MIF SNP-173G>C(rs755622)and the repeat polymorphism CATT5-8(rs5844572)using a predesigned TaqMan SNP assay and capillary electrophoresis,respectively.Data were analysed for single site and haplotype association with IBD risk and phenotype.Meta-analysis was employed,to assess cumulative evidence of association of MIF-173G>C with IBD.All published genotype data for MIF-173G>C in IBD were identified using PubMed and subsequently searching the references of all PubMed-identified studies.Imputed genotypes for MIF-173G>C were generated from the Wellcome Trust Case Control Consortium(and National Institute of Diabetes and Digestive and Kidney Diseases).Separate meta-analyses were performed on Caucasian Crohn’s disease(CD)(3863 patients,6031controls),Caucasian ulcerative colitis(UC)(1260 patients,1987 controls),and East Asian UC(416 patients and 789 controls)datasets using the Mantel-Haenszel method.The New Zealand dataset had 93%power,and the meta-analyses had 100%power to detect an effect size of OR=1.40 atα=0.05,respectively.RESULTS:In our New Zealand dataset,single-site analysis found no evidence of association of MIF polymorphisms with overall risk of CD,UC,and IBD or disease phenotype(all P values>0.05).Haplotype analysis found the CATT5/-173C haplotype occurred at a higher frequency in New Zealand controls compared to IBD patients(0.6 vs 0.01;P=0.03,OR=0.22;95%CI:0.05-0.99),but this association did not survive bonferroni correction.Meta-analysis of our New Zealand MIF-173G>C data with data from seven additional Caucasian datasets using a random effects model found no association of MIF polymorphisms with CD,UC,or overall IBD.Similarly,meta-analysis of all published MIF-173G>C data from East Asian datasets(416UC patients,789 controls)found no association of this promoter polymorphism with UC.

Epidemiological studies of esophageal cancer in the era of genome-wide association studies

Esophageal cancer(EC) caused about 395000 deaths in 2010. China has the most cases of EC and EC is the fourth leading cause of cancer death in China. Esophageal squamous cell carcinoma(ESCC) is the predominant histologic type(90%-95%), while the incidence of esophageal adenocarcinoma(EAC) remains extremely low in China. Traditional epidemiological studies have revealed that environmental carcinogens are risk factors for EC. Molecular epidemiological studies revealed that susceptibility to EC is influenced by both environmental and genetic risk factors. Of all the risk factors for EC, some are associated with the risk of ESCC and others with the risk of EAC. However, the details and mechanisms of risk factors involved in the process for EC are unclear. The advanced methods and techniques used in human genome studies bring a great opportunity for researchers to explore and identify the details of those risk factors or susceptibility genes involved inthe process of EC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era to the era of genome wide association studies(GWAS). Here we review the epidemiological studies of EC(especially ESCC) in the era of GWAS, and provide an overview of the general risk factors and those genomic variants(genes, SNPs, miRNAs, proteins) involved in the process of ESCC.

Genetic polymorphisms and gastric cancer risk: a comprehensive review synopsis from meta-analysis and genome-wide association studies

Objective: In the past few decades, more than 500 reports have been published on the relationship between single nucleotide polymorphisms(SNPs) on candidate genes and gastric cancer(GC) risk. Previous findings have been disputed and are controversial. Therefore, we performed this article to summarize and assess the credibility and strength of genetic polymorphisms on the risk of GC.Methods: We used Web of Science, PubMed, and Medline to identify meta-analyses published before July 30 th, 2018 that assessed associations between variants on candidate genes and the risk of GC. Cumulative epidemiological evidence of statistical associations was assessed combining Venice criteria and a false-positive report probability(FPRP) test.Results: Sixty-one variants demonstrated a significant association with GC risk, whereas 29 demonstrated no association. Nine variants on nine genes were rated as presenting strong cumulative epidemiological evidence for a nominally significant association with GC risk, including APE1(rs1760944), DNMT1(rs16999593), ERCC5(rs751402), GSTT1(null/presence), MDM2(rs2278744), PPARG(rs1801282), TLR4(rs4986790), IL-17 F(rs763780), and CASP8(rs3834129). Eleven SNPs were rated as moderate, and 33 SNPs were rated as weak. We also used the FPRP test to identify 13 noteworthy SNPs in five genome-wide association studies.Conclusions: Sixty-one variants are significantly associated with GC risk, and 29 variants are not associated with GC risk;however, five variants on five genes presented strong evidence for an association upgraded from moderate. Further study of these variants may be needed in the future. Our study also provides referenced information for the genetic predisposition to GC.

Host genetic factors affecting hepatitis B infection outcomes:Insights from genome-wide association studies

The clinical outcome of hepatitis B virus(HBV) infection depends on the success or failure of the immune responses to HBV,and varies widely among individuals,ranging from asymptomatic self-limited infection,inactive carrier state,chronic hepatitis,cirrhosis,hepatocellular carcinoma,to liver failure,depending on the success or failure of immune response to HBV.Genome-wide association studies(GWAS) identified key genetic factors influencing the pathogenesis of HBV-related traits.In this review,we discuss GWAS for persistence of HBV infection,antibody response to hepatitis B vaccine,and HBV-related advanced liver diseases.HBV persistence is associated with multiple genes with diverse roles in immune mechanisms.The strongest associations are found within the classical human leukocyte antigen(HLA) genes,highlighting the central role of antigen presentation in the immune response to HBV.Associated variants affect both epitope binding specificities and expression levels of HLA molecules.Several other susceptibility genes regulate the magnitude of adaptive immune responses,determining immunity vs tolerance.HBV persistence and nonresponse to vaccine share the same risk variants,implying overlapping genetic bases.On the other hand,the risk variants for HBV-related advanced liver diseases are largely different,suggesting different host-virus dynamics in acute vs chronic HBV infections.The findings of these GWAS are likely to pave the way for developing more effective preventive and therapeutic interventions by personalizing the management of HBV infection.

Implications of discoveries from genome-wide association studies in current cardiovascular practice

Genome-wide association studies(GWAS)have identified several genetic variants associated with coronary heart disease(CHD),and variations in plasma lipoproteins and blood pressure(BP).Loci corresponding to CDKN2A/CDKN2B/ANRIL,MTHFD1L,CELSR2,PSRC1 and SORT1 genes have been associated with CHD,and TMEM57,DOCK7,CELSR2,APOB,ABCG5,HMGCR,TRIB1,FADS2/S3,LDLR,NCAN and TOMM40-APOE with total cholesterol.Similarly,CELSR2-PSRC1-SORT1,PCSK9,APOB,HMGCR,NCAN-CILP2-PBX4,LDLR,TOMM40-APOE,and APOC1-APOE are associated with variations in low-density lipoprotein cholesterol levels.Altogether,forty,forty three and twenty loci have been associated with high-density lipoprotein cholesterol,triglycerides and BP phenotypes,respectively.Some of these identified loci are common for all the traits,some do not map to functional genes,and some are located in genes that encode for proteins not previously known to be involved in the biological pathway of the trait.GWAS have been successful at identifying new and unexpected genetic loci common to diseases and traits,thus rapidly providing key novel insights into disease biology.Since genotype information is fixed,with minimum biological variability,it is useful in early life risk prediction.However,these variants explain only a small proportion of the observed variance of these traits.Therefore,the utility of genetic determinants in assessing risk at later stages of life has limited immediate clinical impact.The future application of genetic screening will be in identifying risk groups early in life to direct targeted preventive measures.

Identification of New Resistance Loci Against Sheath Blight Disease in Rice Through Genome-Wide Association Study

Sheath blight(SB) caused by the soil borne pathogen Rhizoctonia solani is one of the most serious global rice diseases. Breeding resistant cultivar is the most economical and effective strategy to control the disease. However, no rice varieties are completely resistant to SB, and only a few reliable quantitative trait loci(QTLs) linked with SB resistance have been identified to date. In this study, we conducted a genome-wide association study(GWAS) of SB resistance using 299 varieties from the rice diversity panel 1(RDP1) that were genotyped using 44 000 high-density single nucleotide polymorphism(SNP) markers. Through artificial inoculation, we found that only 36.5% of the tested varieties displayed resistance or moderate resistance to SB. In particular, the aromatic and aus sub-populations displayed higher SB resistance than the tropical japonica(TRJ), indica and temperate japonica sub-populations. Seven varieties showed similar resistance levels to the resistant control YSBR1. GWAS identified at least 11 SNP loci significantly associated with SB resistance in the three independent trials, leading to the identification of two reliable QTLs, qSB-3 and qSB-6, on chromosomes 3 and 6. Using favorable alleles or haplotypes of significantly associated SNP loci, we estimated that both QTLs had obvious effects on reducing SB disease severity and can be used for enhancing SB resistance, especially in improving SB resistance of TRJ sub-population rice varieties. These results provided important information and genetic materials for developing SB resistant varieties through breeding.

Myopia genetics in genome-wide association and postgenome-wide association study era

Genome-wide association studies(GWAS) of myopia and refractive error have generated exciting results and identified novel risk-associated loci. However, the interpretation of the findings of GWAS of complex diseases is not straightforward and has remained challenging. This review provides a brief summary of the main focus on the advantages and limitations of GWAS of myopia, with potential strategies that may contribute to further insight into the genetics of myopia in the post-GWAS or omics era.

Genome-Wide Association Study for Certain Carcass Traits and Organ Weights in a Large White×Minzhu Intercross Porcine Population

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.

Genome-wide association study of vitamin E in sweet corn kernels

Vitamin E,consisting of tocopherols and tocotrienols,serves as a lipid-soluble antioxidant in sweet corn kernels,providing nutrients to both plants and humans.Though the key genes involved in the vitamin E biosynthesis pathway have been identified in plants,the genetic architecture of vitamin E content in sweet corn kernels remains largely unclear.In the present study,an association panel of 204 inbred lines of sweet corn was constructed.Seven compounds of vitamin E were quantified in sweet corn kernels at 28 days after pollination.A total of 119 loci for vitamin E were identified using a genome-wide association study based on genotyping by sequencing,and a genetic network of vitamin E was constructed.Candidate genes identified were involved mainly in RNA regulation and protein metabolism.The known gene ZmVTE4,encodingγ-tocopherol methyltransferase,was significantly associated with four traits(α-tocopherol,α-tocotrienol,theα/γ-tocopherol ratio,and theα/γ-tocotrienol ratio).The effects of two causative markers on ZmVTE4 were validated by haplotype analysis.Finally,two elite cultivars(Yuetian 9 and Yuetian 22)with a 4.5-fold increase in the sum ofα-andγ-tocopherols were developed by marker-assisted selection,demonstrating the successful biofortification of sweet corn.Three genes(DAHPS,ADT2,and cmu2)involved in chorismate and tyrosine synthesis were significantly associated with theα/γ-tocotrienol ratio.These results shed light on the genetic architecture of vitamin E and may accelerate the nutritional improvement of sweet corn.

Genome-wide association study and genomic prediction of Fusarium ear rot resistance in tropical maize germplasm

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.

Evaluation of maize root growth and genome-wide association studies of root traits in response to low nitrogen supply at seedling emergence

Nitrogen(N) deficiency is one of the main factors limiting maize(Zea mays L.) productivity. Genetic improvement of root traits could improve nitrogen use efficiency. An association panel of 461 maize inbred lines was assayed for root growth at seedling emergence under high-nitrate(HN, 5 mmol L^(-1))and low-nitrate(LN, 0.05 mmol L^(-1)) conditions. Twenty-one root traits and three shoot traits were measured. Under LN conditions, the root-to-shoot ratio, root dry weight, total root length, axial root length,and lateral root length on the primary root were all increased. Under LN conditions, the heritability of the plant traits ranged from 0.43 to 0.82, a range much wider than that of 0.27 to 0.55 observed under HN conditions. The panel was genotyped with 542,796 high-density single-nucleotide polymorphism(SNP) markers. Totally 328 significant SNP markers were identified using either mixed linear model(MLM) or general linear model analysis, with 34 detected by both methods. In the 100-kb intervals flanking these SNP markers, four candidate genes were identified. Under LN conditions, the protoporphyrinogen IX oxidase 2 gene was associated with total root surface area and the DELLA protein-encoding gene was associated with the length of the visible lateral root zone of the primary root. Under HN conditions, a histone deacetylase gene was associated with plant height. Under both LN and HN conditions, the gene encoding MA3 domain-containing protein was associated with the first whorl crown root number. The phenotypic and genetic information from this study may be exploited for genetic improvement of root traits aimed at increasing NUE in maize.

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis

The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Leveraging the potential of big genomic and phenotypic data for genome-wide association mapping in wheat

Genome-wide association mapping studies(GWAS)based on Big Data are a potential approach to improve marker-assisted selection in plant breeding.The number of available phenotypic and genomic data sets in which medium-sized populations of several hundred individuals have been studied is rapidly increasing.Combining these data and using them in GWAS could increase both the power of QTL discovery and the accuracy of estimation of underlying genetic effects,but is hindered by data heterogeneity and lack of interoperability.In this study,we used genomic and phenotypic data sets,focusing on Central European winter wheat populations evaluated for heading date.We explored strategies for integrating these data and subsequently the resulting potential for GWAS.Establishing interoperability between data sets was greatly aided by some overlapping genotypes and a linear relationship between the different phenotyping protocols,resulting in high quality integrated phenotypic data.In this context,genomic prediction proved to be a suitable tool to study relevance of interactions between genotypes and experimental series,which was low in our case.Contrary to expectations,fewer associations between markers and traits were found in the larger combined data than in the individual experimental series.However,the predictive power based on the marker-trait associations of the integrated data set was higher across data sets.Therefore,the results show that the integration of medium-sized to Big Data is an approach to increase the power to detect QTL in GWAS.The results encourage further efforts to standardize and share data in the plant breeding community.