Objective: Several genome-wide screens have been performed in autism spectrum disorders resulting in the identification of numerous putative susceptibility loci. Analyses of pooled primary data should result in an inc...Objective: Several genome-wide screens have been performed in autism spectrum disorders resulting in the identification of numerous putative susceptibility loci. Analyses of pooled primary data should result in an increased sample size and the different study samples have a potential to strengthen the evidence for some earlier identified loci, reveal novel loci, and even to provide information of the general significance of the locus. The objective of this study was to search for potential susceptibility loci for autism, which are supported by two independent samples. Methods: We performed a combined analysis of the primary genome scan data of the Autism Genetic Resource Exchange (AGRE)and Finnish autism samples to reveal susceptibility loci potentially shared by these study samples. Results: In the initial combined data analysis, the best loci (p < 0.05) were observed at 1p12- q25, 3p24- 26, 4q21- 31, 5p15- q12, 6q14- 21, 7q33- 36, 8q22- 24, 17p12q21, and 19p13- q13. The combined analysis of Finnish and AGRE families showed the most promising shared locus on 3p24- 26 with nonparametric logarithm of odds (NPL) score of 2.20 (p = 0.011). The combined data analysis did not provide increased linkage evidence for the earlier identified loci on 3q25- 27 or 17p12- q21. However, the 17pl2- q21 locus remained promising also in the combined sample (NPLall = 2.38, p = 0.0076). Interpretation: Our study of 314 autism families highlights the importance of further analyses on 3p24- 26 locus involving comprehensive molecular genetic analyses of oxytocin receptor gene (OXTR), a positional and functional candidate gene for autism.展开更多
目的 探讨基于二代测序的染色体拷贝数变异技术(CNV-seq)在流产物染色体异常检测中的应用效果和临床意义未明的CNVs变异在流产物病因中的作用。方法 选取2020年1月至2022年12月在沈阳市妇幼保健院因胚胎停育或自然流产,自愿行流产物分...目的 探讨基于二代测序的染色体拷贝数变异技术(CNV-seq)在流产物染色体异常检测中的应用效果和临床意义未明的CNVs变异在流产物病因中的作用。方法 选取2020年1月至2022年12月在沈阳市妇幼保健院因胚胎停育或自然流产,自愿行流产物分析的患者178例,对绒毛或皮肤组织进行DNA提取和CNV-seq检测。对临床意义未明的CNVs变异涉及的基因进行富集分析。结果 178例流产物样本中,致病性CNVs 93例(93/178,52.25%),其中染色体数目异常占46.63%,结构异常占5.62%。不同年龄段患者的致病性CNV与非致病性CNV差异有统计学意义(P=0.046)。染色体数目异常中45,X (16.87%)、69,XNN (12.05%)和47,XN,+16 (12.05%)的发病率位列前三位,双重三体7例,三重三体1例,结构异常中共检出综合征10例。KEGG显著富集的是Pantothenate and CoA biosynthesis (P=0.001),GO显著富集的是MHC class I protein binding I (GO:0042288,P=9.04E-05)。结论 半数以上流产是由染色体异常引起的,CNV-seq利于发现罕见的综合征。对临床意义未明的CNVs涉及的基因进行富集可为寻找流产物标记基因提供新的思路。展开更多
目的运用基因集富集分析(GSEA)探索人表皮生长因子受体2(HER2)基因表达状态对胃癌代谢通路影响情况。方法下载癌症基因组图谱(TCGA)、基因表达综合数据库(GEO)和欧洲生物信息研究所(ArrayExpress)数据库的胃癌转录表达数据库,根据Her2...目的运用基因集富集分析(GSEA)探索人表皮生长因子受体2(HER2)基因表达状态对胃癌代谢通路影响情况。方法下载癌症基因组图谱(TCGA)、基因表达综合数据库(GEO)和欧洲生物信息研究所(ArrayExpress)数据库的胃癌转录表达数据库,根据Her2拷贝数或者表达水平选取高低表达组,应用GSEA软件进行富集分析,取错误发现率q值(FDR q val)<25%和/或名义P值(nom P val)<0.01的代谢通路作为有意义的代谢基因集,结果绘制热图寻找共性。结果在癌症基因组图谱胃腺癌集(TCGA STAD)、GEO数据集(GSE66229)等10个数据库中,Her2的高低表达对对过氧物酶体、N-聚糖生物合成和嘧啶代谢通路基因集有影响(FDR q val<25%且nom P val<0.01),糖基磷脂酰肌醇、甘油磷脂、鞘脂类代谢差异有统计学意义(nom P val<0.01)。结论多个数据库GSEA分析结果提示癌基因Her2的状态与多个代谢通路基因集有相关性。展开更多
文摘Objective: Several genome-wide screens have been performed in autism spectrum disorders resulting in the identification of numerous putative susceptibility loci. Analyses of pooled primary data should result in an increased sample size and the different study samples have a potential to strengthen the evidence for some earlier identified loci, reveal novel loci, and even to provide information of the general significance of the locus. The objective of this study was to search for potential susceptibility loci for autism, which are supported by two independent samples. Methods: We performed a combined analysis of the primary genome scan data of the Autism Genetic Resource Exchange (AGRE)and Finnish autism samples to reveal susceptibility loci potentially shared by these study samples. Results: In the initial combined data analysis, the best loci (p < 0.05) were observed at 1p12- q25, 3p24- 26, 4q21- 31, 5p15- q12, 6q14- 21, 7q33- 36, 8q22- 24, 17p12q21, and 19p13- q13. The combined analysis of Finnish and AGRE families showed the most promising shared locus on 3p24- 26 with nonparametric logarithm of odds (NPL) score of 2.20 (p = 0.011). The combined data analysis did not provide increased linkage evidence for the earlier identified loci on 3q25- 27 or 17p12- q21. However, the 17pl2- q21 locus remained promising also in the combined sample (NPLall = 2.38, p = 0.0076). Interpretation: Our study of 314 autism families highlights the importance of further analyses on 3p24- 26 locus involving comprehensive molecular genetic analyses of oxytocin receptor gene (OXTR), a positional and functional candidate gene for autism.
文摘目的 探讨基于二代测序的染色体拷贝数变异技术(CNV-seq)在流产物染色体异常检测中的应用效果和临床意义未明的CNVs变异在流产物病因中的作用。方法 选取2020年1月至2022年12月在沈阳市妇幼保健院因胚胎停育或自然流产,自愿行流产物分析的患者178例,对绒毛或皮肤组织进行DNA提取和CNV-seq检测。对临床意义未明的CNVs变异涉及的基因进行富集分析。结果 178例流产物样本中,致病性CNVs 93例(93/178,52.25%),其中染色体数目异常占46.63%,结构异常占5.62%。不同年龄段患者的致病性CNV与非致病性CNV差异有统计学意义(P=0.046)。染色体数目异常中45,X (16.87%)、69,XNN (12.05%)和47,XN,+16 (12.05%)的发病率位列前三位,双重三体7例,三重三体1例,结构异常中共检出综合征10例。KEGG显著富集的是Pantothenate and CoA biosynthesis (P=0.001),GO显著富集的是MHC class I protein binding I (GO:0042288,P=9.04E-05)。结论 半数以上流产是由染色体异常引起的,CNV-seq利于发现罕见的综合征。对临床意义未明的CNVs涉及的基因进行富集可为寻找流产物标记基因提供新的思路。
文摘目的运用基因集富集分析(GSEA)探索人表皮生长因子受体2(HER2)基因表达状态对胃癌代谢通路影响情况。方法下载癌症基因组图谱(TCGA)、基因表达综合数据库(GEO)和欧洲生物信息研究所(ArrayExpress)数据库的胃癌转录表达数据库,根据Her2拷贝数或者表达水平选取高低表达组,应用GSEA软件进行富集分析,取错误发现率q值(FDR q val)<25%和/或名义P值(nom P val)<0.01的代谢通路作为有意义的代谢基因集,结果绘制热图寻找共性。结果在癌症基因组图谱胃腺癌集(TCGA STAD)、GEO数据集(GSE66229)等10个数据库中,Her2的高低表达对对过氧物酶体、N-聚糖生物合成和嘧啶代谢通路基因集有影响(FDR q val<25%且nom P val<0.01),糖基磷脂酰肌醇、甘油磷脂、鞘脂类代谢差异有统计学意义(nom P val<0.01)。结论多个数据库GSEA分析结果提示癌基因Her2的状态与多个代谢通路基因集有相关性。
