全基因组关联分析在茶叶研究中的应用进展

全基因组关联分析（genome-wide association analysis,GWAS）是以高通量测序技术为基础,结合生物信息学和统计学方法,在全基因组水平上鉴定调控复杂性状的基因变异,是研究复杂农艺性状和遗传变异最有力和最有效的研究方法,其核心是研究遗传变异和目标性状之间的关联。GWAS研究检测到的关联位点一般很少,而且关联的位点仅能解释很少一部分性状变异。本文介绍了影响GWAS的主要因素,总结了GWAS在茶叶饮料消费、茶树重要农艺性状、茶叶品质和茶树群体结构研究中取得的一系列进展,提出了茶树GWAS研究中遇到的问题和未来的发展方向。     

全基因组混合模型关联分析的极速回归扫描法研究

在全基因组混合模型关联分析(GWMMAS)中,利用剩余多基因遗传力代替方差比值(剩余多基因方差/误差方差),将多基因遗传力求解限制在(0,1)区间内。引入R语言Rcpp Armadillo程序包中的极速线性模型拟合函数(fast Lm Pure函数)快速估计单核苷酸多态性(SNP)效应和完整LMM最大似然值。从由GBLUP估计的性状基因组遗传力出发,逐个高通量SNP的GWMMAS约需4次全基因组回归扫描。当仅关注EMMAX法估计的大效应或高显著水准标记时,GWMMAS运行时间缩短在两次扫描之内。与采用lm函数优化剩余多基因方差比的Fa ST-LMM法相比,极速回归扫描法可成倍提高GWMMAS计算效率。计算机模拟试验证实新方法统计和计算效率,运用极速回归扫描法可高效定位与牙鲆生长性状相关基因位点。     

Identification and validation of novel loci associated with wheat quality through a genome-wide association study

Understanding the genetic basis of quality-related traits contributes to the improvement of grain protein concentration(GPC), grain starch concentration(GSC), and wet gluten concentration(WGC) in wheat. In this study, a genome-wide association study(GWAS) based on a mixed linear model(MLM) was performed on 236 wheat accessions, including 160 cultivars and 76 landraces, using a 55K single nucleotide polymorphism(SNP) array in multiple environments. A total of 12 stable QTL/SNPs that control diffe...     

Genetic dissection of hexanol content in soybean seed through genome-wide association analysis

Hexanol is a major compound contributing to the off-flavors(the bean-like odor) of soybean derived soymilk. The most effective way to reduce the off-flavors of soymilk is the screening and utilization of soybean cultivars with improved hexanol content. However, no genome-wide genetic analysis for this particular trait has been conducted to date. The objective of the present study was to dissect the genetic basis of hexanol content in soybean seed through genome-wide association analysis(GWAS). A total of 105 soybean accessions were analyzed for hexanol content in a three-year experiments and genotyped by sequencing using the specific locus amplified fragment sequencing(SLAF-seq) approach. A total of 25 724 single nucleotide polymorphisms(SNPs) were obtained with minor allele frequencies(MAF)5%. GWAS showed that 25 quantitative trait nucleotides(QTNs) were significantly associated with the hexanol concentration in soybean seed. These identified QTNs distributed on different genomic regions of the 15 chromosomes. A total of 91 genes were predicted as candidate genes underlying the seed hexanol level and six candidates were predicted possibly underlying the seed hexanol by gene based association. In this study, GWAS has been proven to be an effective way to dissect the genetic basis of the hexanol concentration in multiple genetic backgrounds. The identified beneficial alleles and candidate genes might be valuable for the improvement of marker-assisted breeding efficiency for low hexanol level and help to explore possible molecular mechanisms underlying hexanol content in soybean seed.     

A genome-wide association study of five meat quality traits in Yorkshire pigs

Meat quality is an important trait in the pig industry. To identify genomic regions and haplotype blocks responsible for meat quality traits in pigs, a genome-wide association study was conducted for five traits including intramuscular fat content, pH at 45 min and 24 h, drip loss within 24 h and water-holding capacity in 231 Yorkshire barrows using illumina porcine 60k SNP chips. The results showed that a total of 344 single nucleotide polymorphisms (SNP) were significantly associated with five meat quality traits (P<1×10^-4). Moreover, 323 SNPs were within the reported QTL regions, of which 21 were novel. Also, 158 SNPs fell into the proximal region of meat quality related genes. In addition, 25 haplotype blocks based on 116 SNPs were revealed with SNP combination patterns for five traits. Our study added new SNP information for identification of meat quality traits in pigs and will help elucidate the mechanisms of meat quality in pigs.     

Mining of candidate genes for grape berry cracking using a genome-wide association study

Fruit cracking is a common phenomenon during the growth and development of horticultural crops that seriously affects fruit yield and quality. However, there are few studies on the mining of candidate genes related to berry cracking. To better understand the genetic basis of grape berry cracking, we conducted a genome-wide association study(GWAS)of grape varieties. Based on the mixed linear model(MLM), we detected five single nucleotide polymorphism(SNP)loci associated with berry-cracking index ...     

A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants

Identifying the genetic variants that increase the risk of type 2 diabetes (T2D) in humans has been a formidable challenge. Adopting a genome-wide association strategy, we genotyped 1161 Finnish T2D cases and 1174 Finnish normal glucose-tolerant (NGT) controls with >315,000 single-nucleotide polymorphisms (SNPs) and imputed genotypes for an additional >2 million autosomal SNPs. We carried out association analysis with these SNPs to identify genetic variants that predispose to T2D, compared our T2D association results with the results of two similar studies, and genotyped 80 SNPs in an additional 1215 Finnish T2D cases and 1258 Finnish NGT controls. We identify T2D-associated variants in an intergenic region of chromosome 11p12, contribute to the identification of T2D-associated variants near the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T2D risk. This brings the number of T2D loci now confidently identified to at least 10.     

利用全基因组关联分析挖掘粳稻直链淀粉含量调控基因

直链淀粉含量是评价稻米蒸煮食味品质关键指标,挖掘控制该性状QTLs/基因对于改良稻米品质具有重要意义.研究利用295份粳稻种质组成的自然群体为试验材料,测定2019年和2020年稻米直链淀粉含量,结合重测序得到788 396个高质量SNP,利用Tassel 5.0软件混合线性模型(MLM,Q+K)作全基因组关联分析.结果表明,两年共检测到12个与稻米直链淀粉含量相关QTL,分布在水稻第3、4、11和12染色体上,贡献率范围为8.78％～11.62％,其中qAAC4-2和qAAC12-2在两年中重复检测到.进一步针对这两个QTL区间内所有基因作单倍型分析,结合基因注释和前人研究结果,推测LOC_Os04g33640为影响稻米直链淀粉含量新候选基因.     

A genome-wide association study identifies IL23R as an inflammatory bowel disease gene

The inflammatory bowel diseases Crohn's disease and ulcerative colitis are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. To identify genetic factors that might contribute to these disorders, we performed a genome-wide association study. We found a highly significant association between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23. An uncommon coding variant (rs11209026, c.1142G>A, p.Arg381Gln) confers strong protection against Crohn's disease, and additional noncoding IL23R variants are independently associated. Replication studies confirmed IL23R associations in independent cohorts of patients with Crohn's disease or ulcerative colitis. These results and previous studies on the proinflammatory role of IL-23 prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.     

Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes

The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1924 diabetic cases and 2938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3757 additional cases and 5346 controls and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8. Our findings provide insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes.     

数量性状全基因组关联分析中上位效应遗传位点检测方法研究进展

数量性状的表型变异受到大量效应微小的遗传位点和诸多环境因素的共同作用,但在数量性状的遗传研究领域,关于不同遗传位点之间加性效应与上位效应相对重要性的认识却存在着分歧。近年来,伴随着全基因组关联分析在人类及家养动物数量性状研究中的发展,在全基因组关联分析的框架内进行上位效应遗传位点的检测越发受到重视。文章以遗传力失踪问题为出发点,首先综述了标记-QTL连锁分析和GWAS框架下传统上位效应遗传位点的检测方法,然后对基于表型方差同质性检验和广义线性混合模型方法的上位效应统计推断以及混杂因素的处理方法进行了总结与梳理,旨在为数量性状全基因规模上位效应的相关研究提供理论参考。     

滩羊毛色的全基因组关联分析

滩羊不仅肉质鲜美,其所产的二毛裘皮在国内外也享有盛誉,毛色是滩羊重要的经济性状。为检测影响滩羊毛色的基因组区域,利用美国Affymetrix绵羊600K基因分型芯片对宁夏盐池地区具有代表性毛色的96只滩羊个体(全白、白毛黑头、白毛褐或黄头)进行基因分型,并采用Logistic回归方法进行全基因组关联分析。通过Bonferroni校正,检测到5个与毛色显著关联的SNPs。这些SNPs分别位于或邻近2个已知基因(MC1R和TCF25)。其中MC1R基因参与调控黑色素的合成,研究表明其与绵羊毛色相关。而TCF25基因与MC1R基因距离很近,可能由于存在一定程度的连锁不平衡而被鉴定到。本研究进一步解析了滩羊毛色性状的遗传机理,为滩羊毛色性状的标记辅助选育提供科学依据。     

Genetic dissection of the grain-filling rate and related traits through linkage analysis and genome-wide association study in bread wheat

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 GFR₁, 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 QGFRmax2B.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.     

Integration of genome-wide association study and selection signatures reveals genetic determinants for skeletal muscle production traits in an F2 chicken population

Improving the production of broiler chicken meat has been a goal of broiler breeding programs worldwide for many years. However, the genetic architectures of skeletal muscle production traits in chickens have not yet been fully elucidated. In the present study, a total of 519 F₂ birds, derived from a cross of Arbor Acres broiler and Baier layer, were re-sequenced(26 F₀ individuals were re-sequenced at a 10-fold depth; 519 F₂ individuals were re-sequenced at a 3-f...     

Sequence variants in the RNF212 gene associate with genome-wide recombination rate

The genome-wide recombination rate varies between individuals, but the mechanism controlling this variation in humans has remained elusive. A genome-wide search identified sequence variants in the 4p16.3 region correlated with recombination rate in both males and females. These variants are located in the RNF212 gene, a putative ortholog of the ZHP-3 gene that is essential for recombinations and chiasma formation in Caenorhabditis elegans. It is noteworthy that the haplotype formed by two single-nucleotide polymorphisms (SNPs) associated with the highest recombination rate in males is associated with a low recombination rate in females. Consequently, if the frequency of the haplotype changes, the average recombination rate will increase for one sex and decrease for the other, but the sex-averaged recombination rate of the population can stay relatively constant.     

超级杂交稻杂种优势基因组水平的转录因子分析

本研究利用超级杂交稻组合两优培九及亲本(93-11、培矮64S)和已完成基因组测序的籼稻93-11和粳稻日本晴所配的籼粳杂交稻及亲本为材料,采用包含36926个单一基因的的寡聚核苷酸基因芯片进行亲本和杂交组合基因表达差异分析.结果表明在两优培九杂交组合中发现3488个差异表达基因,在Nipponbare/93-11组合中只发现有2416个差异表达基因.差异表达基因表现为多基因修饰模式,主要有加性效应,高或低亲本的显性效应,超显性和低显性.两优培九杂交组合中表现为加性效应有2317个主要差异基因,而Nipponbare/93-11组合中只有1055个主要差异基因表现为加性效应.两个杂交组合的差异表达基因的保守功能包括多个生物化学代谢途径的有关基因.比较亲本同源性基因调控区域发现大量的序列变化,这些变化在差异表达基因中更为丰富.上述发现证明了杂种优势产生的存在较复杂的分子机理.