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 histolo...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.展开更多
Rheumatoid arthritis(RA) is a chronic, inflammatory autoimmune disease sustained by genetic factors. Various aspects of the genetic contribution to the pathogenetics and outcome of RA are still unknown. Several genes ...Rheumatoid arthritis(RA) is a chronic, inflammatory autoimmune disease sustained by genetic factors. Various aspects of the genetic contribution to the pathogenetics and outcome of RA are still unknown. Several genes have been indicated so far in the pathogenesis of RA. Apart from human leukocyte antigen, large genome wide association studies have identified many loci involved in RA pathogenesis. These genes include protein tyrosine phosphatase, nonreceptor type 22, Peptidyl Arginine Deiminase type Ⅳ, signal transducer and activator of transcription 4, cytotoxic T-lymphocyte-associated protein 4, tumor necrosis factor-receptor associated factor 1/complement component 5, tumor necrosis factor and others. It is important to determine whether a combination of RA risk alleles are able to identify patients who will develop certain clinical outcomes, such myocardium infarction, severe infection or lymphoma, as well as to identify patients who will respond to biological medication therapy.展开更多
Diseases are a potential threat to global food security but plants have evolved an extensive array of methodologies to cope with the invading pathogens. Non-host resistance and quantitative re- sistance are broad spec...Diseases are a potential threat to global food security but plants have evolved an extensive array of methodologies to cope with the invading pathogens. Non-host resistance and quantitative re- sistance are broad spectrum forms of resistance, and all kinds of resistances are controlled by extremely diverse genes called ＂R- genes＂. R-genes follow different mechanisms to defend plants and PAMP-induced defenses in susceptible host plants are referred to as basal resistance. Genetic and phenotypic diversity are vital in maize （Zea mays L.）; as such, genome wide association study （GWAS） along with certain other methodologies can explore the maximum means of genetic diversity. Exploring the complete genetic archi- tecture to manipulate maize genetically reduces the losses from hazardous diseases. Genomic studies can reveal the interaction be- tween different genes and their pathways. By confirming the specific role of these genes and protein-protein interaction （proteomics） via advanced molecular and bioinformatics tools, we can shed a light on the most complicated and abstruse phenomena of resistance.展开更多
【目的】玉米穗部性状是产量的重要构成因子,利用全基因组关联分析(genome-wide association study,GWAS)方法解析玉米杂交种穗部性状的遗传基础、挖掘与穗部性状相关的位点,为功能基因克隆和高产玉米品种培育提供参考。【方法】选用11...【目的】玉米穗部性状是产量的重要构成因子,利用全基因组关联分析(genome-wide association study,GWAS)方法解析玉米杂交种穗部性状的遗传基础、挖掘与穗部性状相关的位点,为功能基因克隆和高产玉米品种培育提供参考。【方法】选用115份来源于陕A群和陕B群的优良玉米自交系和4份国内骨干作为亲本,以基于NCⅡ遗传交配设计获得的442份玉米杂交种为材料构建关联群体,调查2个环境中群体材料的穗长、穗粗、穗行数等8个穗部性状;利用tGBS技术检测亲本基因型,推测出F1杂交种的19461个高质量SNP,结合杂交种表型和基因型开展基于加性、显性及上位性模型的穗部性状的全基因组关联分析,并利用公共数据库中玉米穗发育相关组织的转录组数据和基因的注释信息预测候选基因。【结果】表型数据分析结果显示,试验群体的8个穗部性状均符合正态分布,表型变异为3.78%—45.25%。方差分析表明,8个穗部性状的环境效应和基因型效应均呈现极显著水平(P<0.001),广义遗传力为54.15%—68.89%。同时玉米杂交种穗部性状间呈现显著正相关或显著负相关。利用加性和显性模型分别检测到16个和3个显著SNP,上位性模型检测到79个上位性位点。3种模型检测的显著位点累积解释各性状38.21%—60.69%的表型变异,其中,加性模型检测到的显著SNP累积解释的表型变异为0.00—41.26%,上位性模型检测到的位点累积解释的表型变异为15.18%—45.36%。基于加性和显性模型检测的显著SNP的效应分析发现多数位点呈现加性和部分显性效应,仅2个为超显性。进一步分析发现,7个单SNP和5个上位性位点能够解释5%以上的表型变异。根据SNP的位置以及基因的表达信息预测了17个候选基因。【结论】玉米杂交种穗部性状主要受加性、上位性效应影响,显性效应影响较小;加性和显性模型检测的SNP主要表现为加性和部展开更多
全基因组关联研究(Genome wide association study,GWAS)已经在国内外的医学遗传学研究中得到广泛应用,但是GWAS数据中所蕴含的与多基因复杂性状疾病机制相关的丰富信息尚未得到深度挖掘。近年来,研究者采用生物网络分析和生物通路分析...全基因组关联研究(Genome wide association study,GWAS)已经在国内外的医学遗传学研究中得到广泛应用,但是GWAS数据中所蕴含的与多基因复杂性状疾病机制相关的丰富信息尚未得到深度挖掘。近年来,研究者采用生物网络分析和生物通路分析等生物信息学和生物统计学手段分析GWAS数据,并探索潜在的疾病机制。生物网络分析和生物通路分析主要是以基因为单位进行的,因此必须在分析前将基因上全部或者部分单个单核苷酸多态性(Single nucleotide polymorphism,SNP)的遗传关联结果综合起来,即基因水平的关联分析。基因水平的关联分析需要考虑单个SNP的遗传关联、基因上SNP数量和SNP之间的连锁不平衡结构等多种因素,因此不仅在遗传学的概念上也在统计方法方面具有一定的复杂性和挑战性。文章对基因水平的关联分析的研究进展、原理和应用进行了综述。展开更多
文摘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.
文摘Rheumatoid arthritis(RA) is a chronic, inflammatory autoimmune disease sustained by genetic factors. Various aspects of the genetic contribution to the pathogenetics and outcome of RA are still unknown. Several genes have been indicated so far in the pathogenesis of RA. Apart from human leukocyte antigen, large genome wide association studies have identified many loci involved in RA pathogenesis. These genes include protein tyrosine phosphatase, nonreceptor type 22, Peptidyl Arginine Deiminase type Ⅳ, signal transducer and activator of transcription 4, cytotoxic T-lymphocyte-associated protein 4, tumor necrosis factor-receptor associated factor 1/complement component 5, tumor necrosis factor and others. It is important to determine whether a combination of RA risk alleles are able to identify patients who will develop certain clinical outcomes, such myocardium infarction, severe infection or lymphoma, as well as to identify patients who will respond to biological medication therapy.
基金supported by the National Natural Science Foundation of China (31161140347)
文摘Diseases are a potential threat to global food security but plants have evolved an extensive array of methodologies to cope with the invading pathogens. Non-host resistance and quantitative re- sistance are broad spectrum forms of resistance, and all kinds of resistances are controlled by extremely diverse genes called ＂R- genes＂. R-genes follow different mechanisms to defend plants and PAMP-induced defenses in susceptible host plants are referred to as basal resistance. Genetic and phenotypic diversity are vital in maize （Zea mays L.）; as such, genome wide association study （GWAS） along with certain other methodologies can explore the maximum means of genetic diversity. Exploring the complete genetic archi- tecture to manipulate maize genetically reduces the losses from hazardous diseases. Genomic studies can reveal the interaction be- tween different genes and their pathways. By confirming the specific role of these genes and protein-protein interaction （proteomics） via advanced molecular and bioinformatics tools, we can shed a light on the most complicated and abstruse phenomena of resistance.
文摘【目的】玉米穗部性状是产量的重要构成因子,利用全基因组关联分析(genome-wide association study,GWAS)方法解析玉米杂交种穗部性状的遗传基础、挖掘与穗部性状相关的位点,为功能基因克隆和高产玉米品种培育提供参考。【方法】选用115份来源于陕A群和陕B群的优良玉米自交系和4份国内骨干作为亲本,以基于NCⅡ遗传交配设计获得的442份玉米杂交种为材料构建关联群体,调查2个环境中群体材料的穗长、穗粗、穗行数等8个穗部性状;利用tGBS技术检测亲本基因型,推测出F1杂交种的19461个高质量SNP,结合杂交种表型和基因型开展基于加性、显性及上位性模型的穗部性状的全基因组关联分析,并利用公共数据库中玉米穗发育相关组织的转录组数据和基因的注释信息预测候选基因。【结果】表型数据分析结果显示,试验群体的8个穗部性状均符合正态分布,表型变异为3.78%—45.25%。方差分析表明,8个穗部性状的环境效应和基因型效应均呈现极显著水平(P<0.001),广义遗传力为54.15%—68.89%。同时玉米杂交种穗部性状间呈现显著正相关或显著负相关。利用加性和显性模型分别检测到16个和3个显著SNP,上位性模型检测到79个上位性位点。3种模型检测的显著位点累积解释各性状38.21%—60.69%的表型变异,其中,加性模型检测到的显著SNP累积解释的表型变异为0.00—41.26%,上位性模型检测到的位点累积解释的表型变异为15.18%—45.36%。基于加性和显性模型检测的显著SNP的效应分析发现多数位点呈现加性和部分显性效应,仅2个为超显性。进一步分析发现,7个单SNP和5个上位性位点能够解释5%以上的表型变异。根据SNP的位置以及基因的表达信息预测了17个候选基因。【结论】玉米杂交种穗部性状主要受加性、上位性效应影响,显性效应影响较小;加性和显性模型检测的SNP主要表现为加性和部
文摘以100份玉米自交系为材料,通过对2019-2020年山西榆次和太谷两地百粒重数据的测定,计算最佳线性无偏差预测值,结合均匀分布于玉米基因组的44935个SNP标记,基于GLM模型和FarmCPU模型对百粒重进行全基因组关联分析(Genome-wide association study,GWAS)。关联分析结果表明,共鉴定到25个与百粒重显著关联的SNP(P<2.324e^(-5)),其中,关联位点1_274302441、1_298518163和9_32699254位于已定位粒重QTL(Quantitative trait loci)的bin内。在显著SNP位点的连锁不平衡范围内共挖掘出28个候选基因,其中,GRMZM2G116640(乙酰氨基葡萄糖转移酶)、GRMZM2G048733(ABA受体蛋白)、GRMZM2G106424(14-3-3类蛋白)和GRMZM2G024104(谷氨酰胺合成酶)等是重要的百粒重候选基因。
