马铃薯致病疫霉(Phytophthora infestans)属卵菌纲(Oomycetes)霜霉目(Peronosporales)腐霉科(Pythiaceae)疫霉属(Phytophthora),是马铃薯和番茄晚疫病病原菌。由于晚疫病对马铃薯生产的毁灭性和严重性,对致病疫霉的研究一直是关注的重...马铃薯致病疫霉(Phytophthora infestans)属卵菌纲(Oomycetes)霜霉目(Peronosporales)腐霉科(Pythiaceae)疫霉属(Phytophthora),是马铃薯和番茄晚疫病病原菌。由于晚疫病对马铃薯生产的毁灭性和严重性,对致病疫霉的研究一直是关注的重点。本文首先对病害引起的症状、发生特点及流行规律进行阐述,对有性生殖发生的遗传规律和多种交配型共存的大环境下病原菌群体结构变异特点进行归纳总结。随着2009年致病疫霉基因组测序的完成,本文比对了疫霉属目前已完成测序各个种的基因组学特点,介绍了致病疫霉在效应子克隆方面的研究进展及线粒体基因组研究现状,阐述了功能基因组学的两个重要技术:高密度遗传连锁图谱(high density linkage mapping)和全基因组关联分析(genome-wide association study,GWAS),及其在挖掘致病疫霉重要功能基因上的应用。本文有助于了解致病疫霉研究热点及后续突破方向,可为深入解析致病疫霉的功能基因及致病机制提供参考,对开发马铃薯晚疫病菌药物靶标及预测病害的大规模流行趋势也具有重要意义。展开更多
Prostate cancer （PCa） research in China has been on a rocketing trend in recent years. The first genome-wide association study （GWAS） in China identified two new PCa risk associated single nucleotide polymorphisms...Prostate cancer （PCa） research in China has been on a rocketing trend in recent years. The first genome-wide association study （GWAS） in China identified two new PCa risk associated single nucleotide polymorphisms （SNPs）. Next generation sequencing is beginning to be used, yielding novel findings： gene fusions, long non-coding RNAs and other variations. Mechanisms of PCa progression have been illustrated while various diagnosis biomarkers have been investigated extensively. Personalized therapy based on genetic factors, nano-medicine and traditional Chinese medicine has been the focus of experimental therapeutic research for PCa. This review intends to shed light upon the recent progress in PCa research in China and points out the possible breakthroughs in the future.展开更多
全基因组关联研究(Genome-wide association study,GWAS)是人类复杂疾病研究的重要组成部分之一,在群体水平检测全基因组范围的遗传变异与可观测性状间的遗传关联。传统的GWAS是以芯片(Array)技术获得高密度的遗传变异,尽管硕果累累,但...全基因组关联研究(Genome-wide association study,GWAS)是人类复杂疾病研究的重要组成部分之一,在群体水平检测全基因组范围的遗传变异与可观测性状间的遗传关联。传统的GWAS是以芯片(Array)技术获得高密度的遗传变异,尽管硕果累累,但也存在不少问题。如:所谓的"缺失的遗传力",即利用关联分析检测达到全基因组水平显著的遗传变异位点只能解释小部分遗传力;在某些性状上不同研究的结果一致性较弱;显著关联的遗传变异位点的功能较难解释等。高通量测序技术,也称第二代测序(Next-generation sequencing,NGS)技术,可以快速、准确地产出高通量的变异位点数据,为解决以上问题提供了可行的方案。基于NGS技术的GWAS方法(NGS-GWAS)可在一定程度上弥补传统GWAS的不足。文章对NGS-GWAS策略和方法进行了系统性调研,提出了目前较为可行的NGS-GWAS的实施策略和方法,并对NGS-GWAS如何应用于个体化医疗(Personalized medicine,PM)进行了展望。展开更多
我国在精神分裂症的遗传学和生命组学研究方面取得了很大进展,如在全基因组关联分析(genome-wide association study,GWAS)方面工作获得了一系列成果.随着我国对重大疾病转化医学的逐步关注和重视,利用在精神分裂症上已经获得的广泛和...我国在精神分裂症的遗传学和生命组学研究方面取得了很大进展,如在全基因组关联分析(genome-wide association study,GWAS)方面工作获得了一系列成果.随着我国对重大疾病转化医学的逐步关注和重视,利用在精神分裂症上已经获得的广泛和深入的研究结果,寻找精神分裂症各种临床应用的生物标记物研究,系统性地建立适合于类似精神分裂症这类复杂疾病的早期诊断、干预和预防的临床咨询和应用体系等将是该疾病转化医学方面可实施的方法和案例.精神分裂症的转化医学方面还涉及精神分裂症患者的个体化用药方案建立.药物疗效和药物不良反应的个体差异具有较复杂的环境和遗传背景,结合精神分裂症的遗传学病因和药物作用的遗传学差异,将有效发挥治疗药物的功效,并降低重大不良反应在敏感个体上的发生.对精神分裂症这类给国家和社会带来极其重大负担的重大疾病,积极推动我国在此类疾病上的基础研究成果转化和转化医学的实施具有重要的社会效应和积极的带动作用.展开更多
玉米穗轴粗是一个影响玉米产量和穗轴产量的重要性状,其遗传机制的解析可以对高产育种提供指导。本研究以309份玉米自交系为材料,利用测序基因型分型技术对其进行基因型鉴定。采用FarmCPU(fixed and random model circulating probabili...玉米穗轴粗是一个影响玉米产量和穗轴产量的重要性状,其遗传机制的解析可以对高产育种提供指导。本研究以309份玉米自交系为材料,利用测序基因型分型技术对其进行基因型鉴定。采用FarmCPU(fixed and random model circulating probability unification)、MLMM(multiple loci mixed linear model)和CMLM(compressed mixed linear model)方法,对2017年和2019年河南原阳、河南郸城、河南虞城、海南三亚以及最佳线性无偏估计值环境的穗轴粗,进行全基因组关联分析,共鉴定12个与穗轴粗显著关联的SNP(single nucleotide polymorphisms)(P<8.60E-07)。其中,S4_29277313利用FarmCPU和MLMM方法在2017年原阳均检测到。S1_29006330、S2_170889116、S2_2046026464和S4_83821463的表型变异解释率介于10.23%~14.17%,为主效SNP。而且,S1_29006330位于已定位的穗轴粗QTL(quantitative trait loci)区间内。共挖掘17个候选基因,其中WAKL14(wall-associated receptor kinase-like 14)、转录因子ZIM35(zinc-finger protein expressed in inflorescence meristem 35)、HMGA(HMG-Y-related protein A)、组蛋白-赖氨酸N甲基转移酶ATX4(Arabidopsis trithorax 4)和XTH32(xyloglucan endotransglucosylase/hydrolase protein 32),可能是影响穗轴粗的重要基因。挖掘的4个穗轴粗主效SNP和5个候选基因可以为分子标记辅助育种、精细定位和基因克隆提供信息。展开更多
Glucosinolates(GSLs) and their hydrolytic products contribute to the quality traits of rapeseed flowering stalk tissues, such as taste, flavor and anticarcinogenic properties(Glucoraphanin). However, little is known a...Glucosinolates(GSLs) and their hydrolytic products contribute to the quality traits of rapeseed flowering stalk tissues, such as taste, flavor and anticarcinogenic properties(Glucoraphanin). However, little is known about the genetic mechanisms of GSL accumulation in rapeseed flowering stalks. In this study, the variation and genetic architecture of GSL metabolites in flowering stalk tissues were investigated for the first time among a panel of 107 accessions. All GSL compounds exhibited continuous and wide variations in the present population. Progoitrin,glucobrassicanapin and gluconapin were the most abundant GSL compounds. Five quantitative trait loci(QTL) significantly associated with three GSL compounds were identified by genome-wide association study. GRA_C04 was under selected during modern breeding, in which the ratio of lower GSL haplotype(HAP2) in the accessions bred before 1990(52.56%) was significantly lower than that after 1990(78.95%). Four candidate genes, BnaA01. SOT16, BnaA06. SOT17, Bna A06. MYB51a, and Bna A06. MYB51b, were identified in the GTL_A01 and 4OH_A06 regions.These findings provide new insights into GSL biosynthesis in flowering stalk tissues and facilitate quality improvement in rapeseed flowering stalks.展开更多
为了筛选华西牛和雪龙黑牛背最长肌重量相关的遗传标记和候选基因,试验以1478头华西牛和452头雪龙黑牛为研究对象,对其背最长肌重量性状进行全基因组关联分析(genome-wide association study,GWAS),即测定其屠宰后背最长肌重量表型数据...为了筛选华西牛和雪龙黑牛背最长肌重量相关的遗传标记和候选基因,试验以1478头华西牛和452头雪龙黑牛为研究对象,对其背最长肌重量性状进行全基因组关联分析(genome-wide association study,GWAS),即测定其屠宰后背最长肌重量表型数据,利用Illumina Bovine-HD(770K)芯片对其基因组进行基因分型,采用FarmCPU模型和GEMMA模型对质控后的芯片数据进行GWAS,挖掘与华西牛和雪龙黑牛背最长肌重量显著相关的单核苷酸多态性(single nucleotide polymorphism,SNP)位点和候选基因。结果表明:华西牛与雪龙黑牛群体背最长肌重量表型性状均符合正态分布,且二者芯片数据经过质控后分别得到607198,511320个SNP位点,这些SNP位点在二者各个染色体上的分布比较均匀;利用FarmCPU模型在华西牛与雪龙黑牛群体分别检测到12个和9个与其背最长肌重量显著相关的SNP位点,且华西牛群体的显著SNP位点分别位于1,5,7,11,12,13,15,16,22,23号染色体上,鉴定到KCNAB1、PFN2、RNF13、TTLL1、MCAT、CREB3L3、ZBTB7A、MAP2K2、CAMKMT、ZC3H13、OPTN、MCM10、UCMA、OVOL2、PET117、KAT14、MAML2、HHAT、FHIT和LY86共20个候选基因;雪龙黑牛群体的SNP位点分别位于4,16,27号染色体上,鉴定到PCLO、DCTD、WWC2共3个候选基因;利用GEMMA模型在华西牛与雪龙黑牛群体中分别检测到6个与其背最长肌重量显著相关的SNP位点,其中华西牛群体的SNP位点位于13号染色体上,鉴定到GATA3、TAF3、ODAD2、SNX5、MGME1、OVOL2、KAT14、PET117共8个候选基因;雪龙黑牛群体的SNP位点位于1,4,5,25号染色体上,但未鉴定到有效的候选基因。说明在华西牛和雪龙黑牛群体中分别检测到的18个和15个SNP位点与注释到的25个和3个候选基因可作为改良牛背最长肌重量的新的分子标记和候选基因。展开更多
文摘马铃薯致病疫霉(Phytophthora infestans)属卵菌纲(Oomycetes)霜霉目(Peronosporales)腐霉科(Pythiaceae)疫霉属(Phytophthora),是马铃薯和番茄晚疫病病原菌。由于晚疫病对马铃薯生产的毁灭性和严重性,对致病疫霉的研究一直是关注的重点。本文首先对病害引起的症状、发生特点及流行规律进行阐述,对有性生殖发生的遗传规律和多种交配型共存的大环境下病原菌群体结构变异特点进行归纳总结。随着2009年致病疫霉基因组测序的完成,本文比对了疫霉属目前已完成测序各个种的基因组学特点,介绍了致病疫霉在效应子克隆方面的研究进展及线粒体基因组研究现状,阐述了功能基因组学的两个重要技术:高密度遗传连锁图谱(high density linkage mapping)和全基因组关联分析(genome-wide association study,GWAS),及其在挖掘致病疫霉重要功能基因上的应用。本文有助于了解致病疫霉研究热点及后续突破方向,可为深入解析致病疫霉的功能基因及致病机制提供参考,对开发马铃薯晚疫病菌药物靶标及预测病害的大规模流行趋势也具有重要意义。
基金This work was supported by grants from the National Basic Research Program of China （No. 2012CD518300）, the National Natural Science Foundation of China （No. 81101946）, and the Prostate Cancer Foundation Young Investigator Award, and Shanghai Pujiang Program （12PJD008）.
文摘Prostate cancer （PCa） research in China has been on a rocketing trend in recent years. The first genome-wide association study （GWAS） in China identified two new PCa risk associated single nucleotide polymorphisms （SNPs）. Next generation sequencing is beginning to be used, yielding novel findings： gene fusions, long non-coding RNAs and other variations. Mechanisms of PCa progression have been illustrated while various diagnosis biomarkers have been investigated extensively. Personalized therapy based on genetic factors, nano-medicine and traditional Chinese medicine has been the focus of experimental therapeutic research for PCa. This review intends to shed light upon the recent progress in PCa research in China and points out the possible breakthroughs in the future.
文摘全基因组关联研究(Genome-wide association study,GWAS)是人类复杂疾病研究的重要组成部分之一,在群体水平检测全基因组范围的遗传变异与可观测性状间的遗传关联。传统的GWAS是以芯片(Array)技术获得高密度的遗传变异,尽管硕果累累,但也存在不少问题。如:所谓的"缺失的遗传力",即利用关联分析检测达到全基因组水平显著的遗传变异位点只能解释小部分遗传力;在某些性状上不同研究的结果一致性较弱;显著关联的遗传变异位点的功能较难解释等。高通量测序技术,也称第二代测序(Next-generation sequencing,NGS)技术,可以快速、准确地产出高通量的变异位点数据,为解决以上问题提供了可行的方案。基于NGS技术的GWAS方法(NGS-GWAS)可在一定程度上弥补传统GWAS的不足。文章对NGS-GWAS策略和方法进行了系统性调研,提出了目前较为可行的NGS-GWAS的实施策略和方法,并对NGS-GWAS如何应用于个体化医疗(Personalized medicine,PM)进行了展望。
文摘我国在精神分裂症的遗传学和生命组学研究方面取得了很大进展,如在全基因组关联分析(genome-wide association study,GWAS)方面工作获得了一系列成果.随着我国对重大疾病转化医学的逐步关注和重视,利用在精神分裂症上已经获得的广泛和深入的研究结果,寻找精神分裂症各种临床应用的生物标记物研究,系统性地建立适合于类似精神分裂症这类复杂疾病的早期诊断、干预和预防的临床咨询和应用体系等将是该疾病转化医学方面可实施的方法和案例.精神分裂症的转化医学方面还涉及精神分裂症患者的个体化用药方案建立.药物疗效和药物不良反应的个体差异具有较复杂的环境和遗传背景,结合精神分裂症的遗传学病因和药物作用的遗传学差异,将有效发挥治疗药物的功效,并降低重大不良反应在敏感个体上的发生.对精神分裂症这类给国家和社会带来极其重大负担的重大疾病,积极推动我国在此类疾病上的基础研究成果转化和转化医学的实施具有重要的社会效应和积极的带动作用.
文摘玉米穗轴粗是一个影响玉米产量和穗轴产量的重要性状,其遗传机制的解析可以对高产育种提供指导。本研究以309份玉米自交系为材料,利用测序基因型分型技术对其进行基因型鉴定。采用FarmCPU(fixed and random model circulating probability unification)、MLMM(multiple loci mixed linear model)和CMLM(compressed mixed linear model)方法,对2017年和2019年河南原阳、河南郸城、河南虞城、海南三亚以及最佳线性无偏估计值环境的穗轴粗,进行全基因组关联分析,共鉴定12个与穗轴粗显著关联的SNP(single nucleotide polymorphisms)(P<8.60E-07)。其中,S4_29277313利用FarmCPU和MLMM方法在2017年原阳均检测到。S1_29006330、S2_170889116、S2_2046026464和S4_83821463的表型变异解释率介于10.23%~14.17%,为主效SNP。而且,S1_29006330位于已定位的穗轴粗QTL(quantitative trait loci)区间内。共挖掘17个候选基因,其中WAKL14(wall-associated receptor kinase-like 14)、转录因子ZIM35(zinc-finger protein expressed in inflorescence meristem 35)、HMGA(HMG-Y-related protein A)、组蛋白-赖氨酸N甲基转移酶ATX4(Arabidopsis trithorax 4)和XTH32(xyloglucan endotransglucosylase/hydrolase protein 32),可能是影响穗轴粗的重要基因。挖掘的4个穗轴粗主效SNP和5个候选基因可以为分子标记辅助育种、精细定位和基因克隆提供信息。
基金supported by the Key Research and Development project of Hubei Province (Grant Nos. 2020BBB083, 2021BBA097 and 2021BBA102)the National Key Research and Development Program of China (Grant No. 2016YFD0100202)。
文摘Glucosinolates(GSLs) and their hydrolytic products contribute to the quality traits of rapeseed flowering stalk tissues, such as taste, flavor and anticarcinogenic properties(Glucoraphanin). However, little is known about the genetic mechanisms of GSL accumulation in rapeseed flowering stalks. In this study, the variation and genetic architecture of GSL metabolites in flowering stalk tissues were investigated for the first time among a panel of 107 accessions. All GSL compounds exhibited continuous and wide variations in the present population. Progoitrin,glucobrassicanapin and gluconapin were the most abundant GSL compounds. Five quantitative trait loci(QTL) significantly associated with three GSL compounds were identified by genome-wide association study. GRA_C04 was under selected during modern breeding, in which the ratio of lower GSL haplotype(HAP2) in the accessions bred before 1990(52.56%) was significantly lower than that after 1990(78.95%). Four candidate genes, BnaA01. SOT16, BnaA06. SOT17, Bna A06. MYB51a, and Bna A06. MYB51b, were identified in the GTL_A01 and 4OH_A06 regions.These findings provide new insights into GSL biosynthesis in flowering stalk tissues and facilitate quality improvement in rapeseed flowering stalks.
