Understanding the relationship between genotype and phenotype is a major biological question and being able to predict phenotypes based on molecular genotypes is integral to molecular breeding. Whole- genome duplicati...Understanding the relationship between genotype and phenotype is a major biological question and being able to predict phenotypes based on molecular genotypes is integral to molecular breeding. Whole- genome duplications have shaped the history of all flowering plants and present challenges to elucidating the relationship between genotype and phenotype, especially in neopolyploid species. Although single nucleotide polymorphisms （SNPs） have become popular tools for genetic mapping, discovery and appli- cation of SNPs in polyploids has been difficult. Here, we summarize common experimental approaches to SNP calling, highlighting recent polyploid successes. To examine the impact of software choice on these analyses, we called SNPs among five peanut genotypes using different alignment programs （BWA-mem and Bowtie 2） and variant callers （SAMtools, GATK, and Freebayes）. Alignments produced by Bowtie 2 and BWA-mem and analyzed in SAMtools shared 24.5% concordant SNPs, and SAMtools, GATK, and Freebayes shared 1.4% concordant SNPs. A subsequent analysis of simulated Brassica napus chromosome 1A and 1C genotypes demonstrated that, of the three software programs, SAMtools performed with the highest sensitivity and specificity on Bowtie 2 alignments. These results, however, are likely to vary among species, and we therefore propose a series of best practices for SNP calling in polyploids.展开更多
自提出全基因组关联研究(genome-wide association study,GWAS)设想以来,在人类复杂疾病和水稻农艺性状关联研究方面,GWAS已得到广泛运用。但作为一种典型的单标记研究方法,GWAS不能检测小效应的遗传变异,而稀有变异间的联合效应往往与...自提出全基因组关联研究(genome-wide association study,GWAS)设想以来,在人类复杂疾病和水稻农艺性状关联研究方面,GWAS已得到广泛运用。但作为一种典型的单标记研究方法,GWAS不能检测小效应的遗传变异,而稀有变异间的联合效应往往与表型密切相关,因此,需对GWAS结果进行深入的数据挖掘。基于通路的分析方法(pathway-based analysis,PBA)就是利用基因功能、生物代谢通路等相关信息建立的对GWAS结果进行二次挖掘的方法。该方法能从GWAS结果挖掘出与性状、疾病相关联的通路及具有相同功能的基因集等数据,从而获得更多的遗传信息。现对PBA的出现、计算方法和相关软件进行简要综述,以期为人们进行通路分析提供参考。展开更多
为探讨中国汉族人群肿瘤坏死因子受体超家族成员1A基因(tumor necrosis factor receptor superfamily member 1A,TNFRSF1A)rs767455位点多态性(T>C)与脊柱关节病(spondyloarthritides,SpA)患病风险及部分临床指标的关系,采用实时荧...为探讨中国汉族人群肿瘤坏死因子受体超家族成员1A基因(tumor necrosis factor receptor superfamily member 1A,TNFRSF1A)rs767455位点多态性(T>C)与脊柱关节病(spondyloarthritides,SpA)患病风险及部分临床指标的关系,采用实时荧光侵入探针法检测112例SpA患者和82例健康对照的基因型并做关联分析。统计结果显示rs767455位点与SpA患病无显著性关联,但联合中性粒细胞和HLA-B27比单用HLA-B27对SpA发病预测效果更佳(中性粒细胞+HLA-B27 vs HLA-B27,AUC=0.972 vs AUC=0.944,P=0.009)。此外,以本研究样本临床指标均值或中位数作为平均水平分组比较显示,TC型或CC型SpA患者血小板升高的风险显著高于TT型患者(TC+CC vs TT,OR=3.572,95%CI 1.207~10.574,P=0.022),TC型患者血小板高于平均水平的风险同样高于TT型患者(TC vs TT,OR=3.907,95%CI 1.195~12.778,P=0.024)。相对于携带T等位基因患者,C等位基因携带者血小板数目(C vs T,OR=3.000,95%CI 1.143~7.871,P=0.026)、单核细胞数目(C vs T,OR=2.794,95%CI 1.110~7.033,P=0.029)和中性粒细胞数目(C vs T,OR=2.794,95%CI 1.110~7.033,P=0.029)高于平均水平的风险显著升高。在不同组织或细胞样本中的连锁分析显示rs767455是TNFRSF1A的剪接数量性状位点(splicing quantitative trait locus,sQTL)。该研究提示,中性粒细胞可能独立于HLA-B27参与SpA的发病,rs767455位点C等位基因可能通过影响可变剪接参与TNFRSF1A的调控,引起SpA患者中性粒细胞水平升高为代表的免疫失衡,对SpA的致病机制研究和临床精准治疗具有一定指导意义。展开更多
文摘Understanding the relationship between genotype and phenotype is a major biological question and being able to predict phenotypes based on molecular genotypes is integral to molecular breeding. Whole- genome duplications have shaped the history of all flowering plants and present challenges to elucidating the relationship between genotype and phenotype, especially in neopolyploid species. Although single nucleotide polymorphisms （SNPs） have become popular tools for genetic mapping, discovery and appli- cation of SNPs in polyploids has been difficult. Here, we summarize common experimental approaches to SNP calling, highlighting recent polyploid successes. To examine the impact of software choice on these analyses, we called SNPs among five peanut genotypes using different alignment programs （BWA-mem and Bowtie 2） and variant callers （SAMtools, GATK, and Freebayes）. Alignments produced by Bowtie 2 and BWA-mem and analyzed in SAMtools shared 24.5% concordant SNPs, and SAMtools, GATK, and Freebayes shared 1.4% concordant SNPs. A subsequent analysis of simulated Brassica napus chromosome 1A and 1C genotypes demonstrated that, of the three software programs, SAMtools performed with the highest sensitivity and specificity on Bowtie 2 alignments. These results, however, are likely to vary among species, and we therefore propose a series of best practices for SNP calling in polyploids.
文摘自提出全基因组关联研究(genome-wide association study,GWAS)设想以来,在人类复杂疾病和水稻农艺性状关联研究方面,GWAS已得到广泛运用。但作为一种典型的单标记研究方法,GWAS不能检测小效应的遗传变异,而稀有变异间的联合效应往往与表型密切相关,因此,需对GWAS结果进行深入的数据挖掘。基于通路的分析方法(pathway-based analysis,PBA)就是利用基因功能、生物代谢通路等相关信息建立的对GWAS结果进行二次挖掘的方法。该方法能从GWAS结果挖掘出与性状、疾病相关联的通路及具有相同功能的基因集等数据,从而获得更多的遗传信息。现对PBA的出现、计算方法和相关软件进行简要综述,以期为人们进行通路分析提供参考。
文摘为探讨中国汉族人群肿瘤坏死因子受体超家族成员1A基因(tumor necrosis factor receptor superfamily member 1A,TNFRSF1A)rs767455位点多态性(T>C)与脊柱关节病(spondyloarthritides,SpA)患病风险及部分临床指标的关系,采用实时荧光侵入探针法检测112例SpA患者和82例健康对照的基因型并做关联分析。统计结果显示rs767455位点与SpA患病无显著性关联,但联合中性粒细胞和HLA-B27比单用HLA-B27对SpA发病预测效果更佳(中性粒细胞+HLA-B27 vs HLA-B27,AUC=0.972 vs AUC=0.944,P=0.009)。此外,以本研究样本临床指标均值或中位数作为平均水平分组比较显示,TC型或CC型SpA患者血小板升高的风险显著高于TT型患者(TC+CC vs TT,OR=3.572,95%CI 1.207~10.574,P=0.022),TC型患者血小板高于平均水平的风险同样高于TT型患者(TC vs TT,OR=3.907,95%CI 1.195~12.778,P=0.024)。相对于携带T等位基因患者,C等位基因携带者血小板数目(C vs T,OR=3.000,95%CI 1.143~7.871,P=0.026)、单核细胞数目(C vs T,OR=2.794,95%CI 1.110~7.033,P=0.029)和中性粒细胞数目(C vs T,OR=2.794,95%CI 1.110~7.033,P=0.029)高于平均水平的风险显著升高。在不同组织或细胞样本中的连锁分析显示rs767455是TNFRSF1A的剪接数量性状位点(splicing quantitative trait locus,sQTL)。该研究提示,中性粒细胞可能独立于HLA-B27参与SpA的发病,rs767455位点C等位基因可能通过影响可变剪接参与TNFRSF1A的调控,引起SpA患者中性粒细胞水平升高为代表的免疫失衡,对SpA的致病机制研究和临床精准治疗具有一定指导意义。
