Objective:To summarize the application value of copy number variant sequencing(CNV-seq)in the detection of fetal chromosome and cytomegalovirus load.Methods:The study analyzed the clinical basic data,relevant laborato...Objective:To summarize the application value of copy number variant sequencing(CNV-seq)in the detection of fetal chromosome and cytomegalovirus load.Methods:The study analyzed the clinical basic data,relevant laboratory tests,treatment process,and outcomes of three patients with positive cytomegalovirus load detected by CNV-seq for fetal chromosomes and cytomegalovirus load,and literature review was done simutaneoubly.Results:In all three cases,the amniotic fluid cytomegalovirus load was less than 105 Copies/ml,and there were no significant neurological abnormalities observed during pregnancy or postpartum follow-up.There is no literature review on the application of CNV-seq technology in the detection of cytomegalovirus infection,only literature reports on genome analysis of CMV-DNA in confirmed patients were available.Conclusion:CNV-seq can be used to detect cytomegalovirus load,which may have a certain degree of predictive value for fetal outcome.CNV-seq can simultaneously detect fetal chromosomes and pathogenic microorganisms,which is of great significance for the prevention and control of birth defects.展开更多
AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was i...AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was included in the study.Whole-exome sequencing(WES)was initially used to locate copy number variations(CNVs)on 7q31.31-31.32,but failed to detect the precise breakpoint.The long-read sequencing,Oxford Nanopore sequencing Technology(ONT)was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction(QPCR)and Sanger Sequencing.RESULTS:The proband,along with her father and younger brother,were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32,which included the FEVRrelated gene TSPAN12.The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del.The proband exhibited a phase 2A FEVR phenotype,characterized by a falciform retinal fold,macular dragging,and peripheral neovascularization with leaking of fluorescence.These symptoms led to a significant decrease in visual acuity in both eyes.On the other hand,the affected father and younger brother showed a milder phenotype.CONCLUSION:The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype.The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.展开更多
Background:Reproductive performance of livestock is an economically important aspect of global food production.The Chinese Meishan pig is a prolific breed,with an average of three to five more piglets per litter than ...Background:Reproductive performance of livestock is an economically important aspect of global food production.The Chinese Meishan pig is a prolific breed,with an average of three to five more piglets per litter than European breeds;however,the genetic basis for this difference is not well understood.Results:In this study,we investigated copy number variations(CNVs)of 32 Meishan pigs and 29 Duroc pigs by nextgeneration sequencing.A genome-wide analysis of 61 pigs revealed 12,668 copy number variable regions(CNVRs)that were further divided into three categories based on copy number(CN)of the whole population,i.e.,gain(n=7,638),and loss(n=5,030)CNVRs.We then compared Meishan and Duroc pigs and identified 17.17Mb of 6,387 CNVRs that only existing in Meishan pigs CNVRs that overlapped the reproduction-related gene encoding the aryl hydrocarbon receptor(AHR)gene.We found that normal AHR CN was more frequent than CN loss in four different pig breeds.An association analysis showed that AHR CN had a positive effect on litter size(P<0.05)and that a higher CN was associated with higher total number born(P<0.05),number born alive(P<0.05),number of weaned piglets,and birth weight.Conclusions:The present study provides comprehensive CNVRs for Meishan and Duroc pigs through large-scale population resequencing.Our results provide a supplement for the high-resolution map of copy number variation in the porcine genome and valuable information for the investigation of genomic structural variation underlying traits of interest in pig.In addition,the association results provide evidence for AHR as a candidate gene associated with reproductive traits that can be used as a genetic marker in pig breeding programs.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
基金Hainan Natural Science Foundation(821RC699)Hainan Natural Science Foundation(822RC825)+1 种基金Hainan Provincial Health Industry Research Project(22A200242)Key R&D Plan of Hainan Province(ZDYF2020225)。
文摘Objective:To summarize the application value of copy number variant sequencing(CNV-seq)in the detection of fetal chromosome and cytomegalovirus load.Methods:The study analyzed the clinical basic data,relevant laboratory tests,treatment process,and outcomes of three patients with positive cytomegalovirus load detected by CNV-seq for fetal chromosomes and cytomegalovirus load,and literature review was done simutaneoubly.Results:In all three cases,the amniotic fluid cytomegalovirus load was less than 105 Copies/ml,and there were no significant neurological abnormalities observed during pregnancy or postpartum follow-up.There is no literature review on the application of CNV-seq technology in the detection of cytomegalovirus infection,only literature reports on genome analysis of CMV-DNA in confirmed patients were available.Conclusion:CNV-seq can be used to detect cytomegalovirus load,which may have a certain degree of predictive value for fetal outcome.CNV-seq can simultaneously detect fetal chromosomes and pathogenic microorganisms,which is of great significance for the prevention and control of birth defects.
基金Supported by the National Natural Science Foundation of China(No.82060183)Ningxia Natural Science Foundation(No.2022AAC03388)the Key Research and Development Project of Ningxia Hui Autonomous Region(No.2021BEG02045,No.2020BEG03044).
文摘AIM:To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32.METHODS:A family with familial exudative vitreoretinopathy(FEVR)phenotype was included in the study.Whole-exome sequencing(WES)was initially used to locate copy number variations(CNVs)on 7q31.31-31.32,but failed to detect the precise breakpoint.The long-read sequencing,Oxford Nanopore sequencing Technology(ONT)was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction(QPCR)and Sanger Sequencing.RESULTS:The proband,along with her father and younger brother,were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32,which included the FEVRrelated gene TSPAN12.The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del.The proband exhibited a phase 2A FEVR phenotype,characterized by a falciform retinal fold,macular dragging,and peripheral neovascularization with leaking of fluorescence.These symptoms led to a significant decrease in visual acuity in both eyes.On the other hand,the affected father and younger brother showed a milder phenotype.CONCLUSION:The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype.The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.
基金This work was financially supported by National Natural Science Foundations of China(31661143013)National Natural Science Foundation of China(No.31790414)+1 种基金National Key R&D Program of China(2018YFD0501200)and Jinxinnong Animal Science Development Foundation.
文摘Background:Reproductive performance of livestock is an economically important aspect of global food production.The Chinese Meishan pig is a prolific breed,with an average of three to five more piglets per litter than European breeds;however,the genetic basis for this difference is not well understood.Results:In this study,we investigated copy number variations(CNVs)of 32 Meishan pigs and 29 Duroc pigs by nextgeneration sequencing.A genome-wide analysis of 61 pigs revealed 12,668 copy number variable regions(CNVRs)that were further divided into three categories based on copy number(CN)of the whole population,i.e.,gain(n=7,638),and loss(n=5,030)CNVRs.We then compared Meishan and Duroc pigs and identified 17.17Mb of 6,387 CNVRs that only existing in Meishan pigs CNVRs that overlapped the reproduction-related gene encoding the aryl hydrocarbon receptor(AHR)gene.We found that normal AHR CN was more frequent than CN loss in four different pig breeds.An association analysis showed that AHR CN had a positive effect on litter size(P<0.05)and that a higher CN was associated with higher total number born(P<0.05),number born alive(P<0.05),number of weaned piglets,and birth weight.Conclusions:The present study provides comprehensive CNVRs for Meishan and Duroc pigs through large-scale population resequencing.Our results provide a supplement for the high-resolution map of copy number variation in the porcine genome and valuable information for the investigation of genomic structural variation underlying traits of interest in pig.In addition,the association results provide evidence for AHR as a candidate gene associated with reproductive traits that can be used as a genetic marker in pig breeding programs.
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。
