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 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.     

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.     

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。     

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.     

A genome-wide screen identifies genes required for centromeric cohesion

During meiosis, two chromosome segregation phases follow a single round of DNA replication. We identified factors required to establish this specialized cell cycle by examining meiotic chromosome segregation in a collection of yeast strains lacking all nonessential genes. This analysis revealed Sgo1, Chl4, and Iml3 to be important for retaining centromeric cohesin until the onset of anaphase II. Consistent with this role, Sgo1 localizes to centromeric regions but dissociates at the onset of anaphase II. The screen described here provides a comprehensive analysis of the genes required for the meiotic cell cycle and identifies three factors important for the stepwise loss of sister chromatid cohesion.     

用主成分分析法进行数值分类的一些问题

讨论用协方差阵（Σ）和相关阵（Ｒ）进行主成分分析的关系，并初步探套了用主成分分析进行数值分类选用协方差阵和相关阵时应注意的问题     

Splice junctions: association with variation in protein structure

A comparison between eukaryotic gene sequences and protein sequences of homologous enzymes from bacterial and mammalian organisms shows that intron-exon junctions frequently coincide with variable surface loops of the protein structures. The altered surface structures can account for functional differences among the members of a family. Sliding of the intron-exon junctions may constitute one mechanism for generating length polymorphisms and divergent sequences found in protein families. Since intron-exon junctions map to protein surfaces, the alterations mediated by sliding of these junctions can be effected without disrupting the stability of the protein core.     

Visualization of cellulose synthase demonstrates functional association with microtubules

Expression of a functional yellow fluorescent protein fusion to cellulose synthase (CESA) in transgenic Arabidopsis plants allowed the process of cellulose deposition to be visualized in living cells. Spinning disk confocal microscopy revealed that CESA complexes in the plasma membrane moved at constant rates in linear tracks that were aligned and were coincident with cortical microtubules. Within each observed linear track, complex movement was bidirectional. Inhibition of microtubule polymerization changed the fine-scale distribution and pattern of moving CESA complexes in the membrane, indicating a relatively direct mechanism for guidance of cellulose deposition by the cytoskeleton.     

Natural selection shapes genome-wide patterns of copy-number polymorphism in Drosophila melanogaster

The role that natural selection plays in governing the locations and early evolution of copy-number mutations remains largely unexplored. We used high-density full-genome tiling arrays to create a fine-scale genomic map of copy-number polymorphisms (CNPs) in Drosophila melanogaster. We inferred a total of 2658 independent CNPs, 56% of which overlap genes. These include CNPs that are likely to be under positive selection, most notably high-frequency duplications encompassing toxin-response genes. The locations and frequencies of CNPs are strongly shaped by purifying selection, with deletions under stronger purifying selection than duplications. Among duplications, those overlapping exons or introns, as well as those falling on the X chromosome, seem to be subject to stronger purifying selection.