基因组拷贝数变异(copy number variations,CNVs)是指与基因组参考序列相比,基因组中≥1kb的DNA片段插入、缺失和/或扩增,及其互相组合衍生出的复杂变异.由于其具有分布范围广、可遗传、相对稳定和高度异质性等特点,目前认为,CNVs是一...基因组拷贝数变异(copy number variations,CNVs)是指与基因组参考序列相比,基因组中≥1kb的DNA片段插入、缺失和/或扩增,及其互相组合衍生出的复杂变异.由于其具有分布范围广、可遗传、相对稳定和高度异质性等特点,目前认为,CNVs是一种新的可以作为疾病易感标志的基因组DNA多态性,其变异引起的基因剂量改变可以导致表型改变.最近,一种基于CNVs的新的疾病易感基因鉴定策略——CNV全基因组关联分析开始出现,这一策略和传统的基于单核苷酸多态性的关联分析具有互补性,通过认识基因组结构变异可以认识复杂疾病的分子机制和遗传基础.展开更多
2005年至今,全基因组关联研究(Genome-wide association study,GWAS)发现了大量复杂疾病/性状相关变异。近来,科学家们关注的焦点又集中在了如何利用GWAS数据进行深入分析,期待发现更多复杂疾病/性状的易感基因。一些新的策略和方法已...2005年至今,全基因组关联研究(Genome-wide association study,GWAS)发现了大量复杂疾病/性状相关变异。近来,科学家们关注的焦点又集中在了如何利用GWAS数据进行深入分析,期待发现更多复杂疾病/性状的易感基因。一些新的策略和方法已经被尝试应用到复杂疾病/性状GWAS的后续研究中,例如深入分析GWAS数据;鉴定新的复杂疾病/性状易感基因/位点;国际合作和Meta分析;易感区域精细定位及测序;多种疾病共同易感基因研究;以及基因型填补,基于通路的关联分析,基因-基因、基因-环境交互作用和上位研究等。这些策略和方法的应用弥补了经典GWAS的一些不足之处,进一步推动了人类对复杂疾病/性状遗传机制的认识。文章对上述研究的策略、方法以及所面临的问题和挑战进行了综述,为读者描绘了GWAS后期工作的一个简要框架。展开更多
全基因组关联研究(Genome-Wide Association Studies,GWAS)可以直接研究人类行为能力和基因型间的关联,为心理学研究者从全基因组层次探索人类行为能力的遗传基础提供了新的手段。GWAS中涉及大量位点和行为的关联检验,所以必须采用多重...全基因组关联研究(Genome-Wide Association Studies,GWAS)可以直接研究人类行为能力和基因型间的关联,为心理学研究者从全基因组层次探索人类行为能力的遗传基础提供了新的手段。GWAS中涉及大量位点和行为的关联检验,所以必须采用多重校正来控制整体虚报。尽管存在多种校正方法可供选择,但GWAS研究中不同校正方法的适用性,目前尚缺少系统研究,使得GWAS中多重校正方法的选择缺少理论和经验依据。GWAS中常用的校正方法有基于族错误率(Family-Wise Error Rate,FWER)标准的Bonferroni校正法,Holm递减调整法,排列检验法和基于错误发现率(False Discovery Rate,FDR)标准的BH法。对这4种多重校正方法的原理和流程进行了详细阐述;提出了一种GWAS数据仿真方法,并基于仿真数据对不同多重校正方法进行了定量比较。结果显示,前3种基于FWER的方法差别很小,它们对虚报的控制最为严格,但是检测出的真实关联的位点数却显著低于基于FDR的BH法。独立数据上,BH法所报告的SNPs对行为具有最高的解释率,即相对于其它方法,BH方法更好的平衡了虚报和击中。未来研究中可以考虑用BH法来对结果进行校正。展开更多
本研究旨在利用全基因组关联分析方法(genome-wide association studies,GWAS)挖掘影响绵羊体重性状的遗传标记和功能基因。采用Illumina OvineSNP50BeadChip中密度商业化羊芯片,对3个品种(苏尼特羊、德国肉用美利奴羊和杜泊羊)共计329...本研究旨在利用全基因组关联分析方法(genome-wide association studies,GWAS)挖掘影响绵羊体重性状的遗传标记和功能基因。采用Illumina OvineSNP50BeadChip中密度商业化羊芯片,对3个品种(苏尼特羊、德国肉用美利奴羊和杜泊羊)共计329只绵羊的体重性状(初生重、断奶重、6月龄重、断奶前日增重、断奶后日增重、日增重)进行GWAS分析。统计分析和基因注释基于TASSEL软件、混合线性模型和2012年10月公布的最新版绵羊基因组Ovis_aries_v3.1序列信息。结果表明,有10个SNPs位点在全基因组显著水平上与断奶后日增重相关,部分位点分布在羊注释基因内(MEF2B、RFXANK等);除此之外还检测到22个SNPs在染色体显著水平上与其他体重性状存在相关性,获得一批重要的候选基因。这些基因对绵羊体重性状功能基因的挖掘具有重要的理论意义和参考价值。展开更多
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/CDKN2...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.展开更多
全基因组关联分析(genome-wide association studies,GWAS)是一种利用大规模群体的DNA样本进行全基因组高密度基因型分型,探究与目标性状相关联的遗传变异的研究方法。GWAS在揭示猪重要经济性状的变异规律和推动基因组选择在猪育种中的...全基因组关联分析(genome-wide association studies,GWAS)是一种利用大规模群体的DNA样本进行全基因组高密度基因型分型,探究与目标性状相关联的遗传变异的研究方法。GWAS在揭示猪重要经济性状的变异规律和推动基因组选择在猪育种中的实际应用等方面有着重要作用。本综述主要围绕GWAS的基本原理、GWAS的分析方法、GWAS在猪育种方面取得研究进展和其未来展望进行综述,以期为利用GWAS进行猪重要经济性状遗传基础的研究提供参考。展开更多
Several factors influence the clinical course of hepatitis B virus(HBV)and hepatitis C virus(HCV)infection.The human leukocyte antigen(HLA)system,the major histocompatibility complex(MHC)in humans,has been considered ...Several factors influence the clinical course of hepatitis B virus(HBV)and hepatitis C virus(HCV)infection.The human leukocyte antigen(HLA)system,the major histocompatibility complex(MHC)in humans,has been considered one of the most important host factors with respect to outcomes.To date,conventional genotyping studies have shown that HLA classⅡloci are mainly associated with spontaneous clearance of HBV and HCV.However,the specific HLA locus associated with the outcomes of hepatitis virus infection remains unclear.A recent genome-wide association study(GWAS)using a comprehensive approach for human genotyping demonstrated single nucleotide polymorphisms(SNPs)associated with the outcomes of hepatitis virus infection.Examination of large numbers of cohorts revealed that several SNPs in both HLA-DPA1 and HLADPB1 loci are associated with persistent HBV infection in Asian populations.To date,however,few studies have focused on HLA-DP because polymorphisms of HLA-DP haplotype do not vary greatly as compared with other loci of HLA.There are not enough studies to reveal the function of HLA-DP.GWAS additionally detected candidate SNPs within HLA loci associated with chronic HBV or HCV hepatitis,hepatic fibrosis,and the development of hepatocellular carcinoma.The results of one cohort were not always consistent with those of other cohorts.To solve several controversial issues,it is necessary to validate reported SNPs on HLA loci in global populations and to elucidate the HLA-allele-regulated molecular response to hepatitis virus infection.展开更多
文摘基因组拷贝数变异(copy number variations,CNVs)是指与基因组参考序列相比,基因组中≥1kb的DNA片段插入、缺失和/或扩增,及其互相组合衍生出的复杂变异.由于其具有分布范围广、可遗传、相对稳定和高度异质性等特点,目前认为,CNVs是一种新的可以作为疾病易感标志的基因组DNA多态性,其变异引起的基因剂量改变可以导致表型改变.最近,一种基于CNVs的新的疾病易感基因鉴定策略——CNV全基因组关联分析开始出现,这一策略和传统的基于单核苷酸多态性的关联分析具有互补性,通过认识基因组结构变异可以认识复杂疾病的分子机制和遗传基础.
文摘2005年至今,全基因组关联研究(Genome-wide association study,GWAS)发现了大量复杂疾病/性状相关变异。近来,科学家们关注的焦点又集中在了如何利用GWAS数据进行深入分析,期待发现更多复杂疾病/性状的易感基因。一些新的策略和方法已经被尝试应用到复杂疾病/性状GWAS的后续研究中,例如深入分析GWAS数据;鉴定新的复杂疾病/性状易感基因/位点;国际合作和Meta分析;易感区域精细定位及测序;多种疾病共同易感基因研究;以及基因型填补,基于通路的关联分析,基因-基因、基因-环境交互作用和上位研究等。这些策略和方法的应用弥补了经典GWAS的一些不足之处,进一步推动了人类对复杂疾病/性状遗传机制的认识。文章对上述研究的策略、方法以及所面临的问题和挑战进行了综述,为读者描绘了GWAS后期工作的一个简要框架。
文摘本研究旨在利用全基因组关联分析方法(genome-wide association studies,GWAS)挖掘影响绵羊体重性状的遗传标记和功能基因。采用Illumina OvineSNP50BeadChip中密度商业化羊芯片,对3个品种(苏尼特羊、德国肉用美利奴羊和杜泊羊)共计329只绵羊的体重性状(初生重、断奶重、6月龄重、断奶前日增重、断奶后日增重、日增重)进行GWAS分析。统计分析和基因注释基于TASSEL软件、混合线性模型和2012年10月公布的最新版绵羊基因组Ovis_aries_v3.1序列信息。结果表明,有10个SNPs位点在全基因组显著水平上与断奶后日增重相关,部分位点分布在羊注释基因内(MEF2B、RFXANK等);除此之外还检测到22个SNPs在染色体显著水平上与其他体重性状存在相关性,获得一批重要的候选基因。这些基因对绵羊体重性状功能基因的挖掘具有重要的理论意义和参考价值。
基金Supported by A Wellcome Trust Capacity Strengthening Strategic Award to the Public Health Foundation of India and a consortium of UK universities(to Jeemon P)Research grants from National Heart Lung and Blood Institute,United States of America (HHSN286200900026C)National Institute of Health,United States of America(1D43HD065249)(to Prabhakaran D)
文摘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.
文摘全基因组关联分析(genome-wide association studies,GWAS)是一种利用大规模群体的DNA样本进行全基因组高密度基因型分型,探究与目标性状相关联的遗传变异的研究方法。GWAS在揭示猪重要经济性状的变异规律和推动基因组选择在猪育种中的实际应用等方面有着重要作用。本综述主要围绕GWAS的基本原理、GWAS的分析方法、GWAS在猪育种方面取得研究进展和其未来展望进行综述,以期为利用GWAS进行猪重要经济性状遗传基础的研究提供参考。
文摘Several factors influence the clinical course of hepatitis B virus(HBV)and hepatitis C virus(HCV)infection.The human leukocyte antigen(HLA)system,the major histocompatibility complex(MHC)in humans,has been considered one of the most important host factors with respect to outcomes.To date,conventional genotyping studies have shown that HLA classⅡloci are mainly associated with spontaneous clearance of HBV and HCV.However,the specific HLA locus associated with the outcomes of hepatitis virus infection remains unclear.A recent genome-wide association study(GWAS)using a comprehensive approach for human genotyping demonstrated single nucleotide polymorphisms(SNPs)associated with the outcomes of hepatitis virus infection.Examination of large numbers of cohorts revealed that several SNPs in both HLA-DPA1 and HLADPB1 loci are associated with persistent HBV infection in Asian populations.To date,however,few studies have focused on HLA-DP because polymorphisms of HLA-DP haplotype do not vary greatly as compared with other loci of HLA.There are not enough studies to reveal the function of HLA-DP.GWAS additionally detected candidate SNPs within HLA loci associated with chronic HBV or HCV hepatitis,hepatic fibrosis,and the development of hepatocellular carcinoma.The results of one cohort were not always consistent with those of other cohorts.To solve several controversial issues,it is necessary to validate reported SNPs on HLA loci in global populations and to elucidate the HLA-allele-regulated molecular response to hepatitis virus infection.
