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
Objective:Histology grade,subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival.The aim of the study was to investigate the relationship between chromosomal instability,morphol...Objective:Histology grade,subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival.The aim of the study was to investigate the relationship between chromosomal instability,morphological subtypes and the grading system used in lung non-mucinous adenocarcinoma(LNMA).Methods:We developed a whole genome copy number variation(WGCNV)scoring system and applied next generation sequencing to evaluate CNVs present in 91 LNMA tumor samples.Results:Higher histological grades,aggressive subtypes and more advanced TNM staging were associated with an increased WGCNV score,particularly in CNV regions enriched for tumor suppressor genes and oncogenes.In addition,we demonstrate that 24-chromosome CNV profiling can be performed reliably from specific cell types(<100 cells)isolated by sample laser capture microdissection.Conclusions:Our findings suggest that the WGCNV scoring system we developed may have potential value as an adjunct test for predicting the prognosis of patients diagnosed with LNMA.展开更多
Many of our major crop species are polyploids, containing more than one genome or set of chromosomes. Polyploid crops present unique challenges, including difficulties in genome assembly, in discriminating between mul...Many of our major crop species are polyploids, containing more than one genome or set of chromosomes. Polyploid crops present unique challenges, including difficulties in genome assembly, in discriminating between multiple gene and sequence copies, and in genetic mapping, hindering use of genomic data for genetics and breeding. Polyploid genomes may also be more prone to containing structural variation, such as loss of gene copies or sequences(presence–absence variation) and the presence of genes or sequences in multiple copies(copynumber variation). Although the two main types of genomic structural variation commonly identified are presence–absence variation and copy-number variation, we propose that homeologous exchanges constitute a third major form of genomic structural variation in polyploids. Homeologous exchanges involve the replacement of one genomic segment by a similar copy from another genome or ancestrally duplicated region, and are known to be extremely common in polyploids. Detecting all kinds of genomic structural variation is challenging, but recent advances such as optical mapping and long-read sequencing offer potential strategies to help identify structural variants even in complex polyploid genomes. All three major types of genomic structural variation(presence–absence, copy-number, and homeologous exchange) are now known to influence phenotypes in crop plants, with examples of flowering time, frost tolerance, and adaptive and agronomic traits. In this review,we summarize the challenges of genome analysis in polyploid crops, describe the various types of genomic structural variation and the genomics technologies and data that can be used to detect them, and collate information produced to date related to the impact of genomic structural variation on crop phenotypes. We highlight the importance of genomic structural variation for the future genetic improvement of polyploid crops.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
The application of microarray-based techniques for the diagnosis of genomic rearrangements has been steadily growing in popularity since its introduction in 2004.Given the many advantages of these techniques over conv...The application of microarray-based techniques for the diagnosis of genomic rearrangements has been steadily growing in popularity since its introduction in 2004.Given the many advantages of these techniques over conventional cytogenetics,there is increasing pressure towards their application in prenatal diagnosis.However,there remain several important issues that must be addressed.For example,microarray-based techniques(comparative genomic hybridization-based arrays and single nucleotide polymorphism-based arrays) allow detection of even very small genomic imbalances that can determine pathological clinical conditions.In addition,there are other copy number variations which represent normal variation,with no detectable effects on phenotype.Given the still incomplete knowledge of the changes in our genome and the associated phenotypes,microarray-based diagnosis is likely to find variants of uncertain and unknown clinical significance.The interpretation of these variants is now a major challenge for the medical geneticist,who often find it difficult to establish precise correlations between genotype and phenotype.There is sufficient available evidence to justify the use of microarray-based diagnostics for a select number of specific conditions,but there is also an inevitable trend towards ever wider application.It is very important that this drift does not progress in an unchecked and uncontrolled manner under the thrust of commercial interests.Therefore,we recommend that scientific societies be vigilant and take an advisory role in the adopting of these technologies as new scientific knowledge becomes available.展开更多
AIM:To investigate the prognostic role of genomic stability and copy number alterations(CNAs)pancreatic neuroendocrine tumors(Pan NETs).METHODS:A high-resolution array-based comparative genomic hybridization approach ...AIM:To investigate the prognostic role of genomic stability and copy number alterations(CNAs)pancreatic neuroendocrine tumors(Pan NETs).METHODS:A high-resolution array-based comparative genomic hybridization approach was utilized in order to investigate and quantify chromosomal aberrations in a panel of 37 primary Pan NET and 11 metastatic samples.DNA samples were extracted from formalinfixed and paraffin-embedded tumor specimen.Genomic findings were correlated with histopathological and immunohistochemical data.Moreover,the dataset was subjected to employing an unsupervised hierarchical clustering analysis approach utilizing Euclidean distance and average linkage and associations between genomically defined tumor groups and recurrent CNAs or clinicopathological features of the study group were assessed.RESULTS:Numerous chromosomal aberrations were recurrently detected in both,primary tumor samples and metastases.Copy number gains were most frequently observed at 06p22.2-p22.1(27.1%),17p13.1(20.8%),07p21.3-p21.2(18.8%),09q34.11(18.8%).Genomic losses were significantly less frequent and the only recurrent aberration affected 08q24.3(6.3%).Moreover,we detected a high degree of genomic heterogeneity between primary tumors and metastatic lesions.Unsupervised hierarchical clustering of loci affected by CNAs in more than 3 primary tumor samples revealed two genetically distinct tumor groups as well as two chromosomal clusters of genomic imbalances indicating a small subset of tumors with common molecular features(13.5%).Aberrations affecting6p22.2-22.1,8q24.3,9q34.11 and 17p13.1(P=0.011;0.003;0.003;0.001),were significantly associated with a poorer survival prognosis.CONCLUSION:This study suggests that several frequent CNAs in numerous candidate regions are involved in the pathogenesis and metastatic progression of PanNET.展开更多
Rapeseed(Brassica napus,AACC)was formed by hybridization between progenitor species Brassica rapa(AA)and Brassica oleracea(CC).As a result of a limited number of hybridization events between specific progenitor genoty...Rapeseed(Brassica napus,AACC)was formed by hybridization between progenitor species Brassica rapa(AA)and Brassica oleracea(CC).As a result of a limited number of hybridization events between specific progenitor genotypes and strong breeding selection for oil quality traits,rapeseed has limited genetic diversity.The production of resynthesized B.napus lines via interspecific hybridization of the diploid progenitor species B.rapa and B.oleracea is one possible way to increase genetic variation in rapeseed.However,most resynthesized lines produced so far have been reported to be meiotically unstable and infertile,in contrast to established B.napus cultivars.This hinders both maintenance and use of this germplasm in breeding programs.We characterized a large set of 140 resynthesized lines produced by crosses between B.rapa and B.oleracea,as well as between B.rapa and wild C genome species(B.incana,B.hilarionis,B.montana,B.Bourgeaui,B.villosa and B.cretica)for purity(homozygosity),fertility,and genome stability.Self-pollinated seed set,seeds per ten pods as well as percentage pollen viability were used to estimate fertility.SNP genotyping was performed using the Illumina Infinium Brassica 60K array for 116 genotypes,with at least three individuals per line.Most of the material which had been advanced through multiple generations was no longer pure,with heterozygosity detected corresponding to unknown parental contributions via outcrossing.Fertility and genome stability were both genotypedependent.Most lines had high numbers of copy number variants(CNVs),indicative of meiotic instability,and high numbers of CNVs were significantly associated with reduced fertility.Eight putatively stable resynthesized B.napus lines were observed.Further investigation of these lines may reveal the mechanisms underlying this effect.Our results suggest that selection of stable resynthesized lines for breeding purposes is possible.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
Premenstrual dysphoric disorder(PMDD) affects nearly 5% of women of reproductive age. Symptomatic heterogeneity, together with largely unknown genetics, has greatly hindered its effective treatment. In the present stu...Premenstrual dysphoric disorder(PMDD) affects nearly 5% of women of reproductive age. Symptomatic heterogeneity, together with largely unknown genetics, has greatly hindered its effective treatment. In the present study, analysis of genomic sequencing-based copy number variations(CNVs) called from 100 kb white blood cell DNA sequence windows by means of semisupervized clustering led to the segregation of patient genomes into the D and V groups, which correlated with the depression and invasion clinical types,respectively, with 89.0% consistency. Application of diagnostic CNV features selected using the correlation-based machine learning method enabled the classification of the CNVs obtained into the D group, V group, total patient group, and control group with an average accuracy of 83.0%. The power of the diagnostic CNV features was 0.98 on average, suggesting that these CNV features could be used for the molecular diagnosis of the major clinical types of PMDD. This demonstrated concordance between the CNV profiles and clinical types of PMDD supported the validity of symptom-based diagnosis of PMDD for differentiating between its two major clinical types, as well as the predominantly genetic nature of PMDD with a host of overlaps between multiple susceptibility genes/pathways and the diagnostic CNV features as indicators of involvement in PMDD etiology.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:对1例X连锁隐性遗传鱼鳞病合并隐睾的患儿及其家系成员进行遗传学分析,探讨其致病原因。方法:对患儿及其家庭成员进行常规染色体G显带核型分析和低深度全基因组拷贝数变异测序分析(CNV-seq)。结果:染色体核型分析未见明显异常。CNV...目的:对1例X连锁隐性遗传鱼鳞病合并隐睾的患儿及其家系成员进行遗传学分析,探讨其致病原因。方法:对患儿及其家庭成员进行常规染色体G显带核型分析和低深度全基因组拷贝数变异测序分析(CNV-seq)。结果:染色体核型分析未见明显异常。CNV-seq检测发现患儿及哥哥和母亲的X染色体p22.33-p22.31处缺失5.28Mb区域,该片段包含Xp22.31 recurrent region (includes STS)全部。结论:患儿X染色体拷贝数变异遗传自其母亲,Xp22.31缺失是该患儿异常表型的遗传学病因。展开更多
目的:总结拷贝数变异测序(copy number variant sequencing,CNV‐seq)对检测胎儿染色体及巨细胞病毒载量的应用价值。方法:分析CNV‐seq检测胎儿染色体及巨细胞病毒载量的3例巨细胞病毒载量阳性患者的临床基础资料、相关实验室检查、治...目的:总结拷贝数变异测序(copy number variant sequencing,CNV‐seq)对检测胎儿染色体及巨细胞病毒载量的应用价值。方法:分析CNV‐seq检测胎儿染色体及巨细胞病毒载量的3例巨细胞病毒载量阳性患者的临床基础资料、相关实验室检查、治疗过程及转归并文献复习。结果:3例病例中患者羊水巨细胞病毒载量均小于105 Copies/mL,且其孕期临床表现、产后随访均未见明显神经系统异常。文献复习未见有关CNV‐seq技术应用于巨细胞病毒感染的检测,仅有对已确诊患者进行CMV‐DNA的基因组分析的文献报道。结论:CNV‐seq可用于巨细胞病毒载量的检测,其病毒载量对胎儿的结局可能具有一定程度的预判价值。CNV‐seq可同时检测胎儿染色体及病原微生物,对于出生缺陷防控有着重要意义。展开更多
旨在鉴别与鸭重要经济性状潜在相关的拷贝数变异(copy number variations,CNVs),为解析CNVs对鸭经济性状的影响提供前期研究基础。本研究利用从美国国家生物技术信息中心(National Center for Biotechnology Information,NCBI)公共数据...旨在鉴别与鸭重要经济性状潜在相关的拷贝数变异(copy number variations,CNVs),为解析CNVs对鸭经济性状的影响提供前期研究基础。本研究利用从美国国家生物技术信息中心(National Center for Biotechnology Information,NCBI)公共数据库中下载的8个鸭品种共78个个体的全基因组重测序数据,采用CNVnator和CNVcaller软件进行全基因组CNVs检测,同时只保留两个软件检测结果中存在至少1 bp重叠的同类型CNVRs,以消除假阳性对试验结果的影响。结果显示,8个鸭品种的CNVs合并后共检测出7550个CNV regions(CNVRs),其中包括7098个duplications和452个deletions。这些CNVRs在鸭29条常染色体上呈不均匀分布,总长度为16111.2 kb,平均长度为2134 bp,约占鸭基因组的1.51%。此外,本研究在8个鸭品种共筛选到4304个潜在的品种特异性CNVRs,覆盖1230个注释基因。通过基因功能Gene Ontology(GO)富集分析,鉴别到38个可能与生长和繁殖相关的CNVRs。本研究共发现7550个CNVRs,筛选出4304个潜在的品种特异性CNVRs,并鉴别到38个与鸭生长和繁殖潜在相关的CNVRs,为深入探究CNVs对鸭重要经济性状的影响提供了必要的研究基础。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grants from Beijing Hospital Key Research Program(121 Research Program,No.BJ2019-195)。
文摘Objective:Histology grade,subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival.The aim of the study was to investigate the relationship between chromosomal instability,morphological subtypes and the grading system used in lung non-mucinous adenocarcinoma(LNMA).Methods:We developed a whole genome copy number variation(WGCNV)scoring system and applied next generation sequencing to evaluate CNVs present in 91 LNMA tumor samples.Results:Higher histological grades,aggressive subtypes and more advanced TNM staging were associated with an increased WGCNV score,particularly in CNV regions enriched for tumor suppressor genes and oncogenes.In addition,we demonstrate that 24-chromosome CNV profiling can be performed reliably from specific cell types(<100 cells)isolated by sample laser capture microdissection.Conclusions:Our findings suggest that the WGCNV scoring system we developed may have potential value as an adjunct test for predicting the prognosis of patients diagnosed with LNMA.
基金supported by the Deutsche Forschungsgemeinschaft(MA6473/1-1,MA6473/2-1)
文摘Many of our major crop species are polyploids, containing more than one genome or set of chromosomes. Polyploid crops present unique challenges, including difficulties in genome assembly, in discriminating between multiple gene and sequence copies, and in genetic mapping, hindering use of genomic data for genetics and breeding. Polyploid genomes may also be more prone to containing structural variation, such as loss of gene copies or sequences(presence–absence variation) and the presence of genes or sequences in multiple copies(copynumber variation). Although the two main types of genomic structural variation commonly identified are presence–absence variation and copy-number variation, we propose that homeologous exchanges constitute a third major form of genomic structural variation in polyploids. Homeologous exchanges involve the replacement of one genomic segment by a similar copy from another genome or ancestrally duplicated region, and are known to be extremely common in polyploids. Detecting all kinds of genomic structural variation is challenging, but recent advances such as optical mapping and long-read sequencing offer potential strategies to help identify structural variants even in complex polyploid genomes. All three major types of genomic structural variation(presence–absence, copy-number, and homeologous exchange) are now known to influence phenotypes in crop plants, with examples of flowering time, frost tolerance, and adaptive and agronomic traits. In this review,we summarize the challenges of genome analysis in polyploid crops, describe the various types of genomic structural variation and the genomics technologies and data that can be used to detect them, and collate information produced to date related to the impact of genomic structural variation on crop phenotypes. We highlight the importance of genomic structural variation for the future genetic improvement of polyploid crops.
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.
文摘The application of microarray-based techniques for the diagnosis of genomic rearrangements has been steadily growing in popularity since its introduction in 2004.Given the many advantages of these techniques over conventional cytogenetics,there is increasing pressure towards their application in prenatal diagnosis.However,there remain several important issues that must be addressed.For example,microarray-based techniques(comparative genomic hybridization-based arrays and single nucleotide polymorphism-based arrays) allow detection of even very small genomic imbalances that can determine pathological clinical conditions.In addition,there are other copy number variations which represent normal variation,with no detectable effects on phenotype.Given the still incomplete knowledge of the changes in our genome and the associated phenotypes,microarray-based diagnosis is likely to find variants of uncertain and unknown clinical significance.The interpretation of these variants is now a major challenge for the medical geneticist,who often find it difficult to establish precise correlations between genotype and phenotype.There is sufficient available evidence to justify the use of microarray-based diagnostics for a select number of specific conditions,but there is also an inevitable trend towards ever wider application.It is very important that this drift does not progress in an unchecked and uncontrolled manner under the thrust of commercial interests.Therefore,we recommend that scientific societies be vigilant and take an advisory role in the adopting of these technologies as new scientific knowledge becomes available.
基金Supported by Thorns C and Brabant G received research funding from IPSEN Pharma Gmb H(Ettlingen),Germany and Novartis Pharma Gmb H,Nürnberg,Germany
文摘AIM:To investigate the prognostic role of genomic stability and copy number alterations(CNAs)pancreatic neuroendocrine tumors(Pan NETs).METHODS:A high-resolution array-based comparative genomic hybridization approach was utilized in order to investigate and quantify chromosomal aberrations in a panel of 37 primary Pan NET and 11 metastatic samples.DNA samples were extracted from formalinfixed and paraffin-embedded tumor specimen.Genomic findings were correlated with histopathological and immunohistochemical data.Moreover,the dataset was subjected to employing an unsupervised hierarchical clustering analysis approach utilizing Euclidean distance and average linkage and associations between genomically defined tumor groups and recurrent CNAs or clinicopathological features of the study group were assessed.RESULTS:Numerous chromosomal aberrations were recurrently detected in both,primary tumor samples and metastases.Copy number gains were most frequently observed at 06p22.2-p22.1(27.1%),17p13.1(20.8%),07p21.3-p21.2(18.8%),09q34.11(18.8%).Genomic losses were significantly less frequent and the only recurrent aberration affected 08q24.3(6.3%).Moreover,we detected a high degree of genomic heterogeneity between primary tumors and metastatic lesions.Unsupervised hierarchical clustering of loci affected by CNAs in more than 3 primary tumor samples revealed two genetically distinct tumor groups as well as two chromosomal clusters of genomic imbalances indicating a small subset of tumors with common molecular features(13.5%).Aberrations affecting6p22.2-22.1,8q24.3,9q34.11 and 17p13.1(P=0.011;0.003;0.003;0.001),were significantly associated with a poorer survival prognosis.CONCLUSION:This study suggests that several frequent CNAs in numerous candidate regions are involved in the pathogenesis and metastatic progression of PanNET.
基金funded by the German Research Council(DFG grant MA6473/2-1,awarded to AM)The Mason lab is partially funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)under Germany’s Excellence Strategy-EXC 2070-390732324.
文摘Rapeseed(Brassica napus,AACC)was formed by hybridization between progenitor species Brassica rapa(AA)and Brassica oleracea(CC).As a result of a limited number of hybridization events between specific progenitor genotypes and strong breeding selection for oil quality traits,rapeseed has limited genetic diversity.The production of resynthesized B.napus lines via interspecific hybridization of the diploid progenitor species B.rapa and B.oleracea is one possible way to increase genetic variation in rapeseed.However,most resynthesized lines produced so far have been reported to be meiotically unstable and infertile,in contrast to established B.napus cultivars.This hinders both maintenance and use of this germplasm in breeding programs.We characterized a large set of 140 resynthesized lines produced by crosses between B.rapa and B.oleracea,as well as between B.rapa and wild C genome species(B.incana,B.hilarionis,B.montana,B.Bourgeaui,B.villosa and B.cretica)for purity(homozygosity),fertility,and genome stability.Self-pollinated seed set,seeds per ten pods as well as percentage pollen viability were used to estimate fertility.SNP genotyping was performed using the Illumina Infinium Brassica 60K array for 116 genotypes,with at least three individuals per line.Most of the material which had been advanced through multiple generations was no longer pure,with heterozygosity detected corresponding to unknown parental contributions via outcrossing.Fertility and genome stability were both genotypedependent.Most lines had high numbers of copy number variants(CNVs),indicative of meiotic instability,and high numbers of CNVs were significantly associated with reduced fertility.Eight putatively stable resynthesized B.napus lines were observed.Further investigation of these lines may reveal the mechanisms underlying this effect.Our results suggest that selection of stable resynthesized lines for breeding purposes is possible.
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。
基金supported by grants to HX from University Grants Council(SRF116SC01UROP18SC06+10 种基金UROP20SC07)Innovation and Technology Commission(ITS/085/10ITS113/15FPITCPD/17-9ITT/023/17GPITT/026/18GP)of Hong Kong SARShenzhen Municipal Council of Science and Technology,Guangdong(JCYJ20170818113656988)Guangdong Province Basic and Applied Basic Research Fund(2021A1515011169)Shandong Province First Class Disciple Development Grant and Tai-Shan Scholar Program,Shandongand Ministry of Science and Technology(National Science and Technology Major Project,No.2017ZX09301064,2017ZX09301064004)People’s Republic of China,as well as grants from National Natural Science Foundation of China to M.Q.(8157151623)and J.W.(81603510)。
文摘Premenstrual dysphoric disorder(PMDD) affects nearly 5% of women of reproductive age. Symptomatic heterogeneity, together with largely unknown genetics, has greatly hindered its effective treatment. In the present study, analysis of genomic sequencing-based copy number variations(CNVs) called from 100 kb white blood cell DNA sequence windows by means of semisupervized clustering led to the segregation of patient genomes into the D and V groups, which correlated with the depression and invasion clinical types,respectively, with 89.0% consistency. Application of diagnostic CNV features selected using the correlation-based machine learning method enabled the classification of the CNVs obtained into the D group, V group, total patient group, and control group with an average accuracy of 83.0%. The power of the diagnostic CNV features was 0.98 on average, suggesting that these CNV features could be used for the molecular diagnosis of the major clinical types of PMDD. This demonstrated concordance between the CNV profiles and clinical types of PMDD supported the validity of symptom-based diagnosis of PMDD for differentiating between its two major clinical types, as well as the predominantly genetic nature of PMDD with a host of overlaps between multiple susceptibility genes/pathways and the diagnostic CNV features as indicators of involvement in PMDD etiology.
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:对1例X连锁隐性遗传鱼鳞病合并隐睾的患儿及其家系成员进行遗传学分析,探讨其致病原因。方法:对患儿及其家庭成员进行常规染色体G显带核型分析和低深度全基因组拷贝数变异测序分析(CNV-seq)。结果:染色体核型分析未见明显异常。CNV-seq检测发现患儿及哥哥和母亲的X染色体p22.33-p22.31处缺失5.28Mb区域,该片段包含Xp22.31 recurrent region (includes STS)全部。结论:患儿X染色体拷贝数变异遗传自其母亲,Xp22.31缺失是该患儿异常表型的遗传学病因。
文摘目的:总结拷贝数变异测序(copy number variant sequencing,CNV‐seq)对检测胎儿染色体及巨细胞病毒载量的应用价值。方法:分析CNV‐seq检测胎儿染色体及巨细胞病毒载量的3例巨细胞病毒载量阳性患者的临床基础资料、相关实验室检查、治疗过程及转归并文献复习。结果:3例病例中患者羊水巨细胞病毒载量均小于105 Copies/mL,且其孕期临床表现、产后随访均未见明显神经系统异常。文献复习未见有关CNV‐seq技术应用于巨细胞病毒感染的检测,仅有对已确诊患者进行CMV‐DNA的基因组分析的文献报道。结论:CNV‐seq可用于巨细胞病毒载量的检测,其病毒载量对胎儿的结局可能具有一定程度的预判价值。CNV‐seq可同时检测胎儿染色体及病原微生物,对于出生缺陷防控有着重要意义。
文摘旨在鉴别与鸭重要经济性状潜在相关的拷贝数变异(copy number variations,CNVs),为解析CNVs对鸭经济性状的影响提供前期研究基础。本研究利用从美国国家生物技术信息中心(National Center for Biotechnology Information,NCBI)公共数据库中下载的8个鸭品种共78个个体的全基因组重测序数据,采用CNVnator和CNVcaller软件进行全基因组CNVs检测,同时只保留两个软件检测结果中存在至少1 bp重叠的同类型CNVRs,以消除假阳性对试验结果的影响。结果显示,8个鸭品种的CNVs合并后共检测出7550个CNV regions(CNVRs),其中包括7098个duplications和452个deletions。这些CNVRs在鸭29条常染色体上呈不均匀分布,总长度为16111.2 kb,平均长度为2134 bp,约占鸭基因组的1.51%。此外,本研究在8个鸭品种共筛选到4304个潜在的品种特异性CNVRs,覆盖1230个注释基因。通过基因功能Gene Ontology(GO)富集分析,鉴别到38个可能与生长和繁殖相关的CNVRs。本研究共发现7550个CNVRs,筛选出4304个潜在的品种特异性CNVRs,并鉴别到38个与鸭生长和繁殖潜在相关的CNVRs,为深入探究CNVs对鸭重要经济性状的影响提供了必要的研究基础。