Background: Esophageal squamous cell carcinoma(ESCC) is a leading cause of cancer death worldwide and is char?acterized by numerous genetic mutations. TNM staging is not sufficient for predicting patient outcomes. Add...Background: Esophageal squamous cell carcinoma(ESCC) is a leading cause of cancer death worldwide and is char?acterized by numerous genetic mutations. TNM staging is not sufficient for predicting patient outcomes. Addition?ally, ESCC shows poor responsiveness to chemotherapy and radiation. Thus, there is an urgent need to find efficient therapy targets. Previous ESCC high?throughput genomic studies have lacked intensive survival analysis, particularly for copy number variation(CNV) and the genes involved.Main body: In the study "Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis" recently published in the American Journal of Human Genetics, we comprehensively analyzed the effects of CNVs, mutations, and relative gene expression on patient outcomes. To validate our findings for our 67 sequencing samples, we collected a 321?patient retrospective cohort with detailed 5?year follow?up information and carried out univariate and multivariate survival analyses. In addition, the biological functions of the survival predictors in ESCC were investigated both in vitro and in vivo.Conclusions: We found the independent ESCC survival predictors and potential therapy targets. Nevertheless, the effects of numerous low?frequency mutations need to be explored using larger sample sequencing. Overall, con?structing multi?gene prognostic signatures will remain a great challenge in the future.展开更多
Copy number variations have been found in patients with neural tube abnormalities.In this study,we performed genome-wide screening using high-resolution array-based comparative genomic hybridization in three children ...Copy number variations have been found in patients with neural tube abnormalities.In this study,we performed genome-wide screening using high-resolution array-based comparative genomic hybridization in three children with tethered spinal cord syndrome and two healthy parents.Of eight copy number variations,four were non-polymorphic.These non-polymorphic copy number variations were associated with Angelman and Prader-Willi syndromes,and microcephaly.Gene function enrichment analysis revealed that COX8 C,a gene associated with metabolic disorders of the nervous system,was located in the copy number variation region of Patient 1.Our results indicate that array-based comparative genomic hybridization can be used to diagnose tethered spinal cord syndrome.Our results may help determine the pathogenesis of tethered spinal cord syndrome and prevent occurrence of this disease.展开更多
In the past few years, genome-wide association study （GWAS） has made great successes in identifying genetic susceptibility loci underlying many complex diseases and traits. The findings provide important genetic ins...In the past few years, genome-wide association study （GWAS） has made great successes in identifying genetic susceptibility loci underlying many complex diseases and traits. The findings provide important genetic insights into understanding pathogenesis of diseases. In this paper, we present an overview of widely used approaches and strategies for analysis of GWAS, offered a general consideration to deal with GWAS data. The issues regarding data quality control, population structure, association analysis, multiple comparison and visual presentation of GWAS results are discussed; other advanced topics including the issue of missing heritability, meta-analysis, setbased association analysis, copy number variation analysis and GWAS cohort analysis are also briefly introduced.展开更多
目的分析高龄孕妇介入性产前诊断胎儿染色体异常结果的特征。方法回顾性选取2020年1月至2023年6月于唐山市妇幼保健院产前诊断遗传病诊断中心就诊的行羊膜腔穿刺术的638例高龄孕妇作为研究对象,按照孕妇预产年龄分为A组(35~<40岁,n=4...目的分析高龄孕妇介入性产前诊断胎儿染色体异常结果的特征。方法回顾性选取2020年1月至2023年6月于唐山市妇幼保健院产前诊断遗传病诊断中心就诊的行羊膜腔穿刺术的638例高龄孕妇作为研究对象,按照孕妇预产年龄分为A组(35~<40岁,n=463)和B组(≥40岁,n=175),统计2组高龄孕妇羊水细胞染色体核型分析结果和全基因组拷贝数变异测序(copy number variation sequencing,CNV-seq)检测结果。统计学方法采用χ^(2)检验。结果638例高龄孕妇中,羊水细胞染色体异常核型检出率为8.3%(53/638),其中A组和B组的检出率分别为6.9%(32/463)和12.0%(21/175),B组高于A组(χ^(2)=15.241,P<0.05)。CNV-seq检测结果显示,羊水细胞染色体异常拷贝数变异(copy number variation,CNV)检出率为10.2%(65/638),其中A组和B组的检出率分别为8.9%(41/463)和13.7%(24/175),B组高于A组(χ^(2)=13.634,P<0.05)。结论在高龄孕妇中,胎儿染色体异常发生率随着孕妇年龄增长而上升,行产前诊断羊水细胞染色体核型分析及CNV-seq检测可提高胎儿染色体遗传病的检出率。展开更多
通过DNA从头测序分析人胸膜间皮瘤发生的高关联度突变基因。提取恶性胸膜间皮瘤(MPM)组织和正常胸膜组织DNA,构建基因文库,用Illumina HiSeqX Ten PE 150平台测序,将测序结果与人类基因组数据库的参考序列进行比对、注释,并对测序结果...通过DNA从头测序分析人胸膜间皮瘤发生的高关联度突变基因。提取恶性胸膜间皮瘤(MPM)组织和正常胸膜组织DNA,构建基因文库,用Illumina HiSeqX Ten PE 150平台测序,将测序结果与人类基因组数据库的参考序列进行比对、注释,并对测序结果进行过滤、错误率分布检查、GC含量分布检查分析。MPM组织DNA平均过滤37829946 bp,错误率小于0.12%,GC含量占41.17%,而正常胸膜组织DNA平均过滤39089681 bp,错误率小于0.1%,GC含量占41.7%,两者测序质量均在Q 30(≥80%)以上,MPM为87.43%,正常胸膜为88.36%。以上高质量测序数据通过BWA比对到参考基因组(GRCh 37/hg 19),得到最初比对序列,利用重复标记后的比对序列进行覆盖度、深度等统计,覆盖深度达到10 X以上该突变位点可信。结果显示,实验病例XL14覆盖深度达到10 X的占98.59%,覆盖率达到99.83%;对照病例Z5占98.50%,覆盖率达到99.79%。对该序列进行基因注释分析,发现一系列单核苷酸多态性、基因插入缺失、基因结构变异、基因拷贝数变异,筛选出总变异位点数29277个,可能致病的变异位点数22个,致病性的变异位点数5个,不确定变异有害性的位点数为3353个,其余变异位点均为良性。进一步对突变基因进行富集、关联性分析,预测出突变基因TXNDC2与人胸膜间皮瘤的发生高度相关,相关系数达到0.8以上;突变基因PIEN、ABCC1、UGT1A7、UGT1A3、UGT1A4、UGT1A9、ALDH3B1、UGT1A5等与人胸膜间皮瘤有一定关联性,关联度在0~0.2之间。基因TXNDC2、PIEN、ABCC1、UGT1A7、UGT1A3、UGT1A4、UGT1A9、ALDH3B1、UGT1A5的变异可能与人胸膜间皮瘤的发生发展有关。本实验为人胸膜间皮瘤分子诊断提供了参考。展开更多
文摘Background: Esophageal squamous cell carcinoma(ESCC) is a leading cause of cancer death worldwide and is char?acterized by numerous genetic mutations. TNM staging is not sufficient for predicting patient outcomes. Addition?ally, ESCC shows poor responsiveness to chemotherapy and radiation. Thus, there is an urgent need to find efficient therapy targets. Previous ESCC high?throughput genomic studies have lacked intensive survival analysis, particularly for copy number variation(CNV) and the genes involved.Main body: In the study "Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis" recently published in the American Journal of Human Genetics, we comprehensively analyzed the effects of CNVs, mutations, and relative gene expression on patient outcomes. To validate our findings for our 67 sequencing samples, we collected a 321?patient retrospective cohort with detailed 5?year follow?up information and carried out univariate and multivariate survival analyses. In addition, the biological functions of the survival predictors in ESCC were investigated both in vitro and in vivo.Conclusions: We found the independent ESCC survival predictors and potential therapy targets. Nevertheless, the effects of numerous low?frequency mutations need to be explored using larger sample sequencing. Overall, con?structing multi?gene prognostic signatures will remain a great challenge in the future.
文摘Copy number variations have been found in patients with neural tube abnormalities.In this study,we performed genome-wide screening using high-resolution array-based comparative genomic hybridization in three children with tethered spinal cord syndrome and two healthy parents.Of eight copy number variations,four were non-polymorphic.These non-polymorphic copy number variations were associated with Angelman and Prader-Willi syndromes,and microcephaly.Gene function enrichment analysis revealed that COX8 C,a gene associated with metabolic disorders of the nervous system,was located in the copy number variation region of Patient 1.Our results indicate that array-based comparative genomic hybridization can be used to diagnose tethered spinal cord syndrome.Our results may help determine the pathogenesis of tethered spinal cord syndrome and prevent occurrence of this disease.
基金supported by National Natural Science Foundation of China(No.81072389,81373102,81473070 and 81402765)Research Found for the Doctoral Program of Higher Education of China(No.20113234110002)+4 种基金Key Grant of Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.10KJA330034)College Philosophy and Social Science Foundation from Education Department of Jiangsu Province of China(No.2013SJB790059,2013SJD790032)Research Foundation from Xuzhou Medical College(No.2012KJ02)Research and Innovation Project for College Graduates of Jiangsu Province of China(No.CXLX13_574)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘In the past few years, genome-wide association study （GWAS） has made great successes in identifying genetic susceptibility loci underlying many complex diseases and traits. The findings provide important genetic insights into understanding pathogenesis of diseases. In this paper, we present an overview of widely used approaches and strategies for analysis of GWAS, offered a general consideration to deal with GWAS data. The issues regarding data quality control, population structure, association analysis, multiple comparison and visual presentation of GWAS results are discussed; other advanced topics including the issue of missing heritability, meta-analysis, setbased association analysis, copy number variation analysis and GWAS cohort analysis are also briefly introduced.
文摘目的分析高龄孕妇介入性产前诊断胎儿染色体异常结果的特征。方法回顾性选取2020年1月至2023年6月于唐山市妇幼保健院产前诊断遗传病诊断中心就诊的行羊膜腔穿刺术的638例高龄孕妇作为研究对象,按照孕妇预产年龄分为A组(35~<40岁,n=463)和B组(≥40岁,n=175),统计2组高龄孕妇羊水细胞染色体核型分析结果和全基因组拷贝数变异测序(copy number variation sequencing,CNV-seq)检测结果。统计学方法采用χ^(2)检验。结果638例高龄孕妇中,羊水细胞染色体异常核型检出率为8.3%(53/638),其中A组和B组的检出率分别为6.9%(32/463)和12.0%(21/175),B组高于A组(χ^(2)=15.241,P<0.05)。CNV-seq检测结果显示,羊水细胞染色体异常拷贝数变异(copy number variation,CNV)检出率为10.2%(65/638),其中A组和B组的检出率分别为8.9%(41/463)和13.7%(24/175),B组高于A组(χ^(2)=13.634,P<0.05)。结论在高龄孕妇中,胎儿染色体异常发生率随着孕妇年龄增长而上升,行产前诊断羊水细胞染色体核型分析及CNV-seq检测可提高胎儿染色体遗传病的检出率。
