Relationship Between Gene-Phenotype and Clinical Manifestations of Chromosomal Copy Number Variations Indicated by Non-Invasive Prenatal Testing

Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of chromosomal copy number variations.Methods:3551 naturally conceived singleton pregnant women who underwent NIPT were included in this study.The NIPT revealed abnormalities other than sex chromosome abnormalities and trisomy 13,18,and 21.Pregnant women with chromosome copy number variations underwent genetic counseling and prenatal ultrasound examination.Interventional prenatal diagnosis and chromosome microarray analysis(CMA)were performed.The clinical phenotypes and pregnancy outcomes of different prenatal diagnoses were analyzed.Additionally,a follow-up was conducted by telephone to track fetal development after birth,at six months,and one year post-birth.Results:A total of 53 cases among 3551 cases showed chromosomal copy number variation.Interventional prenatal diagnosis was performed in 36 cases:27 cases were negative and 8 were consistent with the NIPT test results.This indicates that NIPT’s positive predictive value(PPV)in CNVs is 22.22%.Conclusion:NIPT has certain clinical significance in screening chromosome copy number variations and is expected to become a routine screening for chromosomal microdeletions and microduplications.However,further interventional prenatal diagnosis is still needed to identify fetal CNVs.

Low-depth whole genome sequencing reveals copy number variations associated with higher pathologic grading and more aggressive subtypes of lung non-mucinous adenocarcinoma

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.

Scan of the endogenous retrovirus sequences across the swine genome and survey of their copy number variation and sequence diversity among various Chinese and Western pig breeds

In pig-to-human xenotransplantation,the transmission risk of porcine endogenous retroviruses(PERVs)is of great concern.However,the distribution of PERVs in pig genomes,their genetic variation among Eurasian pigs,and their evolutionary history remain unclear.We scanned PERVs in the current pig reference genome(assembly Build 11.1),and identified 36 long complete or near-complete PERVs(lc PERVs)and 23 short incomplete PERVs(si PERVs).Besides three known PERVs(PERV-A,-B,and-C),four novel types(PERV-JX1,-JX2,-JX3,and-JX4)were detected in this study.According to evolutionary analyses,the newly discovered PERVs were more ancient,and PERV-Bs probably experienced a bottleneck~0.5 million years ago(Ma).By analyzing63 high-quality porcine whole-genome resequencing data,we found that the PERV copy numbers in Chinese pigs were lower(32.0±4.0)than in Western pigs(49.1±6.5).Additionally,the PERV sequence diversity was lower in Chinese pigs than in Western pigs.Regarding the lc PERV copy numbers,PERV-A and-JX2 in Western pigs were higher than in Chinese pigs.Notably,Bama Xiang(BMX)pigs had the lowest PERV copy number(27.8±5.1),and a BMX individual had no PERV-C and the lowest PERV copy number(23),suggesting that BMX pigs were more suitable for screening and/or modification as xenograft donors.Furthermore,we identified 451 PERV transposon insertion polymorphisms(TIPs),of which 86 were shared by all 10 Chinese and Western pig breeds.Our findings provide systematic insights into the genomic distribution,variation,evolution,and possible biological function of PERVs.

Association between TLR7 copy number variations and hepatitis B virus infection outcome in Chinese

AIM To explore whether copy number variations (CNVs) of toll-like receptor 7 (TLR7) are associated with susceptibility to chronic hepatitis B virus (HBV) infection. METHODS This study included 623 patients (495 males and 128 females) with chronic hepatitis B virus infection (CHB) and 300 patients (135 females and 165 males) with acute hepatitis B virus infection (AHB) as controls. All CHB patients were further categorized according to disease progression after HBV infection (CHB, liver cirrhosis, or hepatocellular carcinoma). Copy numbers of the TLR7 gene were measured using the AccuCopy method chi(2) tests were used to evaluate the association between TLR7 CNVs and infection type. P values, odds ratios, and 95% confidence intervals (CIs) were used to estimate the effects of risk. RESULTS Among male patients, there were significant differences between the AHB group and CHB group in the distribution of TLR7 CNVs. Low copy numberof TLR7 was significantly associated with chronic HBV infection (OR = 0.329, 95% CI: 0.229-0.473, P > 0.001). Difference in TLR7 copy number was also found between AHB and CHB female patients, with low copy number again associated with an increased risk of chronic HBV infection (OR = 0.292, 95% CI: 0.173- 0.492, P < 0.001). However, there were no significant differences in TLR7 copy number among the three types of chronic HBV infection (CHB, liver cirrhosis, or hepatocellular carcinoma). In addition, there was no association between TLR7 copy number and titer of the HBV e antigen. CONCLUSION Low TLR7 copy number is a risk factor for chronic HBV infection but is not associated with later stages of disease progression.

Copy number variation of B1 controls awn length in wheat

Wheat awns contribute to photosynthesis and grain production.In this study,an F2population and F2:3families from a cross between the awned line 7D12 and the Chinese awnless variety Shiyou 20(SY20)were used to identify loci associated with awn length.Bulked-segregant RNA sequencing and linkage mapping identified a single dominant locus in a 0.3 cM interval on chromosome 5AL.Five genes were in the interval,including the recently cloned awn inhibitor B1.Although a single copy of the B1 gene was detected in 7D12,SY20 carried five copies of the gene.Increased copy number of B1 in SY20enhanced gene expression.Based on sequence variation among the promoter regions of five B1 gene copies in SY20,two dominant markers were developed and found to cosegregate with B1 in a population of 931 wheat accessions.All 77 awnless accessions harbored sequence variations in the B1 promoter regions similar to those of SY20 and thus carried multiple copies of the gene,whereas 15 randomly selected awned wheats carried only one copy.These results suggest that an increase in copy number of the B1 gene is associated with inhibition of awn length.

AB015.The relationship between copy number variations and high myopia in Chinese:a case-control study

As a complex disease,myopia is the most common eye disease worldwide.Many myopia susceptibility genes or variants have been successfully identified in the past years by genome-wide genetic association studies(GWAS),which focus mainly on the single-nucleotide polymorphisms.Little attention has been paid to examine the role of copy number variations(CNVs)in refractive error and myopia.This study adopted a systematic strategy to investigate the role of CNVs in high myopia.In the discovery phase,a pilot GWAS suggests putative CNVs for follow-up.Multiplex ligation-dependent probe amplification was then used to quantify the copy number of 89 CNV segments in 737 case-control samples in the second phase and then 24 top-ranking CNVs in a second group of 1,029 case-control samples in the final validation phase.This validation phase identified 22 significant CNVs.Further work is needed to examine the role of these few CNVs in myopia development.

SMARCC1 copy number variation is related to metastatic colon cancer:an investigation based on TCGA data

Objective There are no well-defined genetic indicators for distant metastatic illness in patients with colon cancer(CC).The discovery of genetic changes linked to metastatic CC might aid in the development of systemic and local therapeutic approaches.Using The Cancer Genome Atlas(TCGA),we examined the relationship between copy number variation(CNV)of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily C member 1(SMARCC1)and distant metastatic illness in patients with CC.Methods Genetic sequencing data of all relevant CC patients and clinical features were collected from TCGA using R.There were 506 CC patients with CNV and clinical outcome data.The CNV of SMARCC1 was examined for its correlation with distant metastatic disease using the TCGA CC dataset(M1 vs.M0).After adjusting for age,sex,T stage,N stage,adjuvant chemotherapy,microsatellite instability(MSI),and surgical margin status,univariate and multivariate logistic regression analyses were performed.Results SMARCC1 CNV was linked to distant metastatic disease(P=0.012 and 0.008 in univariate and multivariate analysis,respectively);positive lymph nodes and margin status were also associated with distal metastases(all P<0.01).MSI,T stage,N stage,adjuvant treatment,sex,race,and MSI were not associated with metastases(all P>0.05).Conclusion SMARCC1 CNV is associated with distant metastatic disease in patients with CC.In individuals with CC,such genetic profiles might be utilized therapeutically to support optimal systemic treatment options against local treatments for CC,such as radiation therapy,pending additional confirmation.

Copy number variation sequencing for diagnosis of cytomegalovirus infection based low-depth whole-genome sequencing technology in fetus:Three cases and literature review

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.

A proteomic approach to investigate the qualitative and quantitative polymorphism of <i>β</i>-lactoglobulin in ovine milk: Inference on gene copy-number variations

The rationale of this work is based on recent evidences suggesting that: 1) both qualitative and quantitative β-lactoglobulin (β-LG) polymorphism may be found in bovine milk;2) quantitative polymorphisms are often the result of expression gradients in multiple copies of a gene;3) the β-LG gene is duplicated in the dog and bovine genome;4) mammary genes are highly conserved across Mammalia. Thus, an investigation was conducted on ovine β-LG polymorphism checking phenotypic evidence for copy-number variants of β-LG in sheep. To the purpose, 206 milk samples were collected, during a small-scale survey within sheep farms breeding Southern Italian breeds. PAGIF screening of the samples revealed that approximately 50% individuals exhibited β-LG polymorphism and 4 different quantitative patterns, which were characterized in detail by a proteomic approach relying on combined chromatographic and mass spectrometric techniques. The expected figures based on the expression gradient models were compared with well-established α-globin gene arrangements in sheep. The different phenotypes suggest the presence of both duplicate and triplicate BLG haplotypes. The occurrence of a triplicate haplotype was supported by population data. The current study supports the helpfulness of up-to-date proteomics for inferring copy number polymorphisms through the characterization of the phenotypic expression.

Genetic Copy Number Variations in Colon Mucosa Indicating Risk for Colorectal Cancer

Background: Sporadic colorectal tumors probably carry genetic alterations that may be related to familiar clusters according to risk loci visualized by SNP arrays on normal tissues. The aim of the present study was therefore to search for DNA regions (copy number variations, CNVs) as biomarkers associated to genetic susceptibility for early risk predictions of colorectal cancer. Such sequence alterations could provide additional information on phenotypic grouping of patients. Material and Methods: High resolution 105K oligonucleotide microarrays were used in search for CNV loci in DNA from tumor-free colon mucosa at primary operations for colon cancer in 60 unselected patients in comparison to DNA in buffy coat cells from 44 confirmed tumor-free and healthy blood donors. Array-detected CNVs were confirmed by Multiplex ligation-dependent probe amplification (MLPA). Results: A total number of 205 potential CNVs were present in DNA from colon mucosa. 184 (90%) of the 205 potential CNVs had been identified earlier in mucosa DNA from healthy individuals as reported to the Database of Genomic Variants. Remaining 21 (10%) CNVs were potentially novel sites. Two CNVs (3q23 and 10q21.1) were significantly related to colon cancer, but not confirmed in buffy coat DNA from the cancer patients. Conclusion: Our study reveals two CNVs that indicate increased risk for colon cancer;These DNA alterations may have? been acquired by colon stem cells with subsequent appearance among epithelial mucosa cells. Impact: Certain mucosa CNV alterations may indicate individual susceptibility for malignant transformation in relationship to intestinal toxins and bacterial growth.

胎儿末端染色体非平衡易位遗传方式的CNV-seq联合G显带核型分析

目的:通过拷贝数变异检测(CNV-seq)联合G显带核型分析对产前诊断和流产的胎儿末端染色体非平衡易位发生频率以及遗传方式进行分析。方法:选取2018年6月至2021年12月在郑州大学第一附属医院经CNV-Seq判定为末端染色体非平衡易位的病例,采用外周血G显带核型分析或FISH检测对胎儿父母进行溯源分析。结果:17248例产前诊断和流产病例中,88例检出末端染色体非平衡易位,检出率为0.51%。其中59例行父母G显带核型分析或FISH检测,32例(54.24%)是由于父母为平衡易位导致,27例(45.76%)为新发变异。结论:诊断为末端染色体非平衡易位的病例,父母行G显带核型分析或FISH检测可提高染色体平衡易位携带者的检出率。

CNV-seq结合STR技术在稽留流产遗传学病因分析中的应用

目的 本研究旨在评估将低深度全基因组拷贝数变异测序(copy number variation sequencing, CNV-seq)技术与短串联重复序列(short tandem repeat, STR)技术联合应用于稽留流产患者流产组织遗传学病因分析的效果。方法 收集2019年1月至2022年11月期间因“胚胎停育”而终止妊娠的49例稽留流产患者进行CNV-seq技术和STR分型技术的联合检测。结果 研究发现孕妇流产次数≥2次组的胚胎染色体异常率明显高于流产次数<2次组,差异有统计学意义(62.1%vs 30.0%,P<0.05),而高龄孕妇组与非高龄孕妇组的胚胎染色体的异常率差异无统计学意义(70%vs 66.7%,P>0.05)。在49例流产物中,CNV-seq结合STR技术共检出34例染色体异常,检出率为69.4%(34/49)。其中染色体数目异常的有20例,包括13例非整倍体,5例多倍体(STR技术)和2例嵌合体;染色体结构异常共有14例,其中5例检出为致病性CNV。此外,还检测到了10例临床意义不明(variants of uncertain significance,VUS)的CNV。结论 将低深度CNV-seq技术与STR技术相结合,可以有效地弥补稽留流产的染色体核型分辨率低和培养难度大等缺点,并提高检测稽留流产胚胎异常染色体的能力,明确稽留流产的遗传学病因,为再次妊娠提供更准确的指导。

Variation_91720拷贝数变异与食管鳞癌易感性的关联研究

目的探讨PIK3CA基因中Variation_91720拷贝数变异（copy number variation,CNV）与中国西南地区汉族人群食管鳞状细胞癌（esophageal squamous cell carcinoma,ESCC）易感性的关联。方法选取149例中国西南地区ESCC患者和205例年龄、性别相匹配的健康人群作为研究对象,采用基于Taq Man实时定量PCR检测外周血中Variation_91720拷贝数;基于SYBR Green实时定量PCR检测34例ESCC患者癌及癌旁组织中PIK3CA基因mRNA表达量。结果Variation_91720拷贝数在ESCC患者和对照人群中分布有显著差异（P〈0.01）,ESCC患者中Variation_91720拷贝数减少频率显著高于对照人群（P〈0.01,OR=5.617,95%CI=2.750-11.470）,是ESCC发生的危险因素;Variation_91720拷贝数增加显著低于对照人群（P=0.028,OR=0.419,95%CI=0.193-0.911）,是ESCC发生的保护因素。34例ESCC患者中癌组织的PIK3CA基因mRNA表达量显著高于癌旁组织（P=0.038）,基因表达差异与相应的外周血基因组Variation_91720拷贝数变异之间无显著统计学差异（P=0.066）。结论 Variation_91720拷贝数变异与中国西南地区汉族人群ESCC的易感性相关联;其拷贝数减少与增加ESCC的易感性相关而其拷贝数增加与降低ESCC的易感性相关,可能成为ESCC的高危人群筛选和早期诊断生物标记物。

The role of genomic structural variation in the genetic improvement of polyploid crops

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.

Identification of chloroquine resistance Pfcrt-K76T and determination of Pfmdr1-N86Y copy number by SYBR Green I qPCR

Objective:To identify prevalence of chloroquine resistance point mutation at(Pfcrt,K76T)and(Pfindr1.N86Y) copy number variation.Methods:SYBR Green I based real time PCR was used.One hundred and thirty-three samples were analyzed for(Pfcrt,K76T) and(Pfmdr1.N86Y) copy number from dried blood spot.Parasite DNA was extracted using high pure DNA preparation kit.The amplification of DNA was done by using AccuPower 2* GreenStar '' qPCR Master mix.For quantification purpose a new primer pair was designed for 178 base pair template from complete genome sequence of Plasmodium falciparum strain 3D7 at NCBI.Absolute quantification method was used to determine the Pfmdr1-N86 Y copy number variations.Standard curve was built from strain3D7 gDNA since it has single copy of Pfindr1 per haploid genome.The known positive controls with single and multi-copy number of Pfindr1 gene were included in each experiment.The copy number ratio of the samples to the standard calibrator was made to obtain the fold difference among the samples with respect to copy number variation.Results:Out of 133 samples 73(54.89%) were confirmed as mutant(Pfcrt,76T) and the remaining 60(45.11%) were genotyped as wild type(Pfcrt,K76).The(Pfindr1.N86Y) copy number variation was determined for 133 clinical samples.Out of these samples 61(45.86%)had single copy and the remaining 72(54.14%) had multi-copy numbers higher than 1.5 copies per genome.Thirty-four(25.56%) multi-copies were between 1.5 and 2.5 copies per genome while 38(28.57%) were more than 2.5 copies per genome.The minimum and maximum copies per genome were 0.474 and 4.741.respectively.Conclusions:The study showed high prevalence level and fixation of Pfcrt.76 T mutation after chloroquine withdrawal.The prevalence of Pfindr1 copy number variant suggested that the presence of modulating factor for emergence of Plasmodium falciparum strains with higher copy numbers.However,the prevalence level was not statistically significant.

应用脑脊液mNGS-CNV分析辅助诊断合并脑积水的脑膜癌病1例报告

本文报道1例脑膜癌病患者的诊疗过程,患者老年男性,慢性病程,进行性加重,主要临床表现为进行性加重的头痛、恶心、呕吐30 d,加重9 d。头部影像学提示脑积水、脑室扩张,对脑脊液进行病原宏基因组二代测序(mNGS)结合人源序列的染色体拷贝数变异(CNV)分析,结果提示病原检测阴性,而人源序列中存在异常非整倍体,高度提示恶性肿瘤;后给予患者脑室留置Ommaya囊,反复送检脑脊液细胞学检测数次提示异型细胞;根据临床表现、脑脊液细胞学以及拷贝数变异分析结果,确诊脑膜癌病。提示mNGS-CNV分析对于诊断脑膜癌病具有重要意义。希望本例患者诊疗过程的梳理,可为脑膜癌病的诊断和治疗等提供参考。

CNV-seq结合染色体核型分析技术在产前诊断胎儿染色体异常中的价值观察

目的探讨基因组拷贝数变异测序(CNV-seq)结合染色体核型分析技术在产前诊断胎儿染色体异常中的价值。方法回顾性选取2019年6月至2022年6月于绵阳市人民医院产前诊断科行羊膜腔穿刺术且拷贝数变异(CNV)提示异常的107例孕妇为研究对象,分别行CNV-seq检测和染色体核型分析。结果在107例孕妇的羊水样本中,染色体核型分析检出58例(54.21%)胎儿核型异常,包括染色体数目异常36例(62.07%),染色体结构异常11例(18.97%),嵌合体11例(18.97%)。CNV-seq检测对染色体核型分析中的58例核型异常者均成功确诊,变异类型包括54例(93.10%)致病性,4例(6.90%)临床意义不明;CNV-seq检出13例嵌合体病例,其中2例(低于10%)染色体核型分析未检出。在49例核型未见异常羊水样本中,CNV-seq检出致病性变异类型20例(40.82%)、临床意义不明23例(46.94%)、可能良性2例(4.08%)、可能致病性1例(2.04%)、良性变异3例(6.12%)。染色体核型分析产前诊断胎儿染色体异常的阳性率均明显低于CNV-seq检测及二者联合检测的阳性率(χ^(2)=115.654,P<0.05);三种检测方法产前诊断胎儿染色体数目异常、染色体结构异常和嵌合体的检出率比较差异均无统计学意义(P>0.05)。结论在胎儿染色体异常的产前诊断中,CNV-seq可高效、特异地检出染色体核型分析技术无法检出的致病性基因组CNVs,可为产前遗传咨询提供更详细的参考信息。

De novel heterozygous copy number deletion on 7q31.31-7q31.32 involving TSPAN12 gene with familial exudative vitreoretinopathy in a Chinese family

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.

Integrated Analysis of the Gene Expression Profiling and Copy Number Aberration of the Ovarian Cancer

Objective: DNA copy number alterations and difference expression are frequently observed in ovarian cancer. The purpose of this way was to pinpoint gene expression change that was associated with alterations in DNA copy number and could therefore enlighten some potential oncogenes and stability genes with functional roles in cancers, and investigated the bioinformatics significance for those correlated genes. Method: We obtained the DNA copy number and mRNA expression data from the Cancer Genomic Atlas and identified the most statistically significant copy number alteration regions using the GISTIC. Then identified the significance genes between the tumor samples within the copy number alteration regions and analyzed the correlation using a binary matrix. The selected genes were subjected to bioinformatics analysis using GSEA tool. Results: GISTIC analysis results showed there were 45 significance copy number amplification regions in the ovarian cancer, SAM and Fisher’s exact test found there have 40 genes can affect the expression level, which located in the amplification regions. That means we obtained 40 genes which have a correlation between copy number amplification and drastic up- and down-expression, which p-value < 0.05 (Fisher’s exact test) and an FDR < 0.05. GSEA enrichment analysis found these genes were overlapped with the several published studies which were focused on the gene study of tumorigenesis. Conclusion: The use of statistics and bioinformatics to analyze the microarray data can found an interaction network involved. The combination of the copy number data and expression has provided a short list of candidate genes that are consistent with tumor driving roles. These would offer new ideas for early diagnosis and treat target of ovarian cancer.

染色体核型分析联合CNV-Seq检测在高龄孕妇产前诊断中的应用

目的探讨染色体核型分析与全基因组拷贝数变异测序(CNV-Seq)技术在高龄孕妇产前诊断中联合应用的意义。方法对2020年1月至2022年12月该院收治的723例高龄孕妇的羊水细胞染色体核型分析、CNV-Seq检测结果进行回顾性分析。结果723例高龄孕妇中检出染色体异常共29例,异常检出率为4.0%。723例高龄孕妇中检出核型异常21例,异常检出率为2.9%,其中染色体非整倍体13例,包括21-三体7例,18-三体1例,性染色体非整倍体5例;染色体嵌合3例,包括性染色体嵌合2例,常染色体嵌合1例;染色体结构异常5例,包括染色体倒位3例,染色体易位2例;检出CNV-Seq异常24例,异常检出率为3.3%,其中染色体非整倍体13例,包括21-三体7例,18-三体1例,性染色体非整倍体5例;染色体嵌合3例,包括性染色体嵌合2例,常染色体嵌合1例;致病性染色体拷贝数变异8例,包括染色体微重复1例,染色体微缺失7例。其中染色体非整倍体异常中染色体核型分析和CNV-Seq检测结果一致。结论染色体核型分析联合CNV-Seq检测可提高染色体异常检出率,两种方法各自有独特的优势,可以相互验证,互补不足,染色体核型分析可比较直观地检测出染色体结构变异,而CNV-Seq可检测出染色体微缺失、微重复。