Genome-wide investigation to assess copy number variants in the Italian local chicken population

Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure of livestock.High-density chips have enabled the detection of CNV with increased resolution,leading to the identification of even small CNV.This study aimed to identify CNV in local Italian chicken breeds and investigate their distribution across the genome.Results Copy number variants were mainly distributed across the first six chromosomes and primarily associated with loss type CNV.The majority of CNV in the investigated breeds were of types 0 and 1,and the minimum length of CNV was significantly larger than that reported in previous studies.Interestingly,a high proportion of the length of chromosome 16 was covered by copy number variation regions(CNVR),with the major histocompatibility complex being the likely cause.Among the genes identified within CNVR,only those present in at least five animals across breeds(n=95)were discussed to reduce the focus on redundant CNV.Some of these genes have been associated to functional traits in chickens.Notably,several CNVR on different chromosomes harbor genes related to muscle development,tissue-specific biological processes,heat stress resistance,and immune response.Quantitative trait loci(QTL)were also analyzed to investigate potential overlapping with the identified CNVR:54 out of the 95 gene-containing regions overlapped with 428 QTL associated to body weight and size,carcass characteristics,egg production,egg components,fat deposition,and feed intake.Conclusions The genomic phenomena reported in this study that can cause changes in the distribution of CNV within the genome over time and the comparison of these differences in CNVR of the local chicken breeds could help in preserving these genetic resources.

Diagnostic yield of third eye retroscope on adenoma detection during colonoscopy:A systematic review and meta-analysis

AIM： To determine the diagnostic yield of the “third eye retroscope”, on adenoma detection rate during screening colonoscopy.METHODS： The “third eye retroscope” when used with standard colonoscopy provides an additional retro-grade view to visualize lesions on the proximal aspects of folds and fexures. We searched MEDLINE （PubMed and Ovid）, SCOPUS （including MEDLINE and EMBASE databases）, Cochrane Database of Systemic Reviews, Google Scholar, and CINAHL Plus databases to identify studies that evaluated diagnostic yield of “third eye retroscope” during screening colonoscopy. DerSimonian Laird random effects model was used to generate the overall effect for each outcome. We evaluated statistical heterogeneity among the studies by using the Cochran Q statistic and quantifed by I2 statistics.RESULTS： Four distinct studies with a total of 920 pa-tients, mean age 59.83 （95%CI： 56.77-62.83） years, were included in the review. The additional adenoma detection rate （AADR） defined as the number of ad-ditional adenomas identified due to “third eye retro-scope” device in comparison to standard colonoscopy alone was 19.9% （95%CI： 7.3-43.9）. AADR for right and left colon were 13.9% （95%CI： 9.4-20） and 10.7 （95%CI： 1.9-42）, respectively. AADR for polyps ≥ 6 mm and ≥ 10 mm were 24.6% （95%CI： 16.6-34.9） and 24.2% （95%CI： 12.9-40.8）, respectively. The ad-ditional polyp detection rate defined as the number of additional polyps identifed due to “third eye retro-scope” device in comparison to standard colonoscopyalone was 19.8% （95%CI： 7.9-41.8）. There were no complications reported with use of “third eye retro-scope” device.CONCLUSION： The “third eye retroscope” device when used with standard colonoscopy is safe and de-tects 19.9% additional adenomas, compared to stan-dard colonoscopy alone.

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.

图像抠图与copy-paste结合的数据增强方法

提出一种基于图像抠图与copy-paste结合的数据增强方法(matting-paste),采用图像抠图法获取单个垃圾实例的准确轮廓,并对单个实例进行旋转和亮度变换.根据物体轮廓信息,把实例粘贴到背景图上,无需额外的人工标注即可生成新的带有标注的数据,从而提高数据集的多样性和复杂性.结果表明:数据集扩充后的mask比数据集扩充前的识别精度提高了0.039,matting-paste能在已有数据集上有效地扩充数据,进一步提高模型的识别精度.

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.

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.

Benchmark Dose Assessment for Coke Oven Emissions-Induced Mitochondrial DNA Copy Number Damage Effects

Objective The study aimed to estimate the benchmark dose(BMD)of coke oven emissions(COEs)exposure based on mitochondrial damage with the mitochondrial DNA copy number(mtDNAcn)as a biomarker.Methods A total of 782 subjects were recruited,including 238 controls and 544 exposed workers.The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction.Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95%confidence lower limit(BMDL).Results The mtDNAcn of the exposure group was lower than that of the control group(0.60±0.29 vs.1.03±0.31;P<0.001).A dose-response relationship was shown between the mtDNAcn damage and COEs.Using the Benchmark Dose Software,the occupational exposure limits(OELs)for COEs exposure in males was 0.00190 mg/m^(3).The OELs for COEs exposure using the BBMD were 0.00170 mg/m^(3)for the total population,0.00158 mg/m^(3)for males,and 0.00174 mg/m^(3)for females.In possible risk obtained from animal studies(PROAST),the OELs of the total population,males,and females were 0.00184,0.00178,and 0.00192 mg/m^(3),respectively.Conclusion Based on our conservative estimate,the BMDL of mitochondrial damage caused by COEs is0.002 mg/m^(3).This value will provide a benchmark for determining possible OELs.

Metaheuristics with Optimal Deep Transfer Learning Based Copy-Move Forgery Detection Technique

The extensive availability of advanced digital image technologies and image editing tools has simplified the way of manipulating the image content.An effective technique for tampering the identification is the copy-move forgery.Conventional image processing techniques generally search for the patterns linked to the fake content and restrict the usage in massive data classification.Contrast-ingly,deep learning(DL)models have demonstrated significant performance over the other statistical techniques.With this motivation,this paper presents an Optimal Deep Transfer Learning based Copy Move Forgery Detection(ODTL-CMFD)technique.The presented ODTL-CMFD technique aims to derive a DL model for the classification of target images into the original and the forged/tampered,and then localize the copy moved regions.To perform the feature extraction process,the political optimizer(PO)with Mobile Networks(MobileNet)model has been derived for generating a set of useful vectors.Finally,an enhanced bird swarm algorithm(EBSA)with least square support vector machine(LS-SVM)model has been employed for classifying the digital images into the original or the forged ones.The utilization of the EBSA algorithm helps to properly modify the parameters contained in the Multiclass Support Vector Machine(MSVM)technique and thereby enhance the classification performance.For ensuring the enhanced performance of the ODTL-CMFD technique,a series of simulations have been performed against the benchmark MICC-F220,MICC-F2000,and MICC-F600 datasets.The experimental results have demonstrated the improvised performance of the ODTL-CMFD approach over the other techniques in terms of several evaluation measures.

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.

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。

“Mimēsis”的辩证法:阿多诺对“技术”的媒介美学批判

在阿多诺针对大众媒介技术展开的现代美学批判中,“Mimēsis”(摹仿)的辩证法是核心向度之一。在对本雅明关于技术复制与现代艺术命运关系之思考的容受中,通过指认技术复制是“摹仿的绝对化”而真正艺术是“摹仿行为的庇护所”,阿多诺揭示了“摹仿”在技术时代的美学中仍然能够作为一个批判概念得以存留的可能性和必要性。其根本原因在于:作为摹仿绝对化的技术复制无论其表面上多么繁荣多样,其实质只是“重复”;但如果媒介技术的“复制”功能成为技术时代艺术的重要摹仿对象,在生产差异之“重复”的“摹仿辩证法”中,复制的技术便可以被艺术的摹仿技艺所吸收转化,从而实现技术的美学“救赎”。

基于改进显著图和局部特征匹配的copy-move窜改检测

检测整幅窜改图像的方法增加了许多非必要的计算量,为了降低计算复杂度和进一步提高检测精确率,提出了一种基于改进显著图和局部特征匹配的copy-move窜改检测方法。首先,结合图像梯度改进显著图,分离出包含图像高纹理信息的局部显著区域;其次,只对该局部区域采用SIFT(scale invariant feature transform)算法提取特征点;然后,对显著性小的图像采用密度聚类和二阶段匹配策略,对显著性大的图像采用超像素分割和显著块特征匹配的策略;最后,结合PSNR和形态学操作来定位窜改区域。在两个公开数据集上进行实验,该方法的平均检测时间小于10 s,平均检测精确率大于97%,均优于所对比的方法。实验结果表明,该方法能够大幅缩减检测时间、有效提高检测精确率,并且对几何变换和后处理操作也都具有较好的鲁棒性。

基于知识增强的开放域多轮对话模型

如何减轻安全回复和重复回复一直是开放域多轮对话模型的两大挑战性难题.然而,现有开放域对话模型往往忽略了对话目标的引导性作用,以及如何在对话历史和对话目标中引入和选择更精确的知识信息.鉴于此,提出基于知识增强的多轮对话模型.所提模型首先将对话历史中实词进行义原及领域词替换,达到消除歧义和丰富对话文本表示的效果.然后将经过知识增强后的对话历史、扩充的三元组世界知识、知识管理和知识拷贝加以集成,以融合知识、词汇、对话历史和对话目标多种信息,生成多样性回复.通过两个国际基准开放域汉语对话语料库上的实验结果及可视化验证所提模型同时在自动评测和人工评测上的有效性.

简易应对方式量表在女性尿失禁患者中的信效度检验

目的探讨简易应对方式量表(SCSQ)在女性尿失禁(UI)患者人群中的信效度。方法招募社区女性UI居民316人,进行SCSQ等量表的评估,用题总相关系数分析量表的项目,采用Cronbach'sα系数进行信度分析,相关分析检验校标效度,因子分析检验结构效度、聚敛效度、区分效度。结果SCSQ在女性UI患者中应用时,需要做适当修订,修订版SCSQ总量表Cronbach'sα为0.89,积极应对分量表Cronbach'sα为090,消极应对分量表Cronbach's α为0.75。积极应对维度分量表得分与SSRS得分成正相关(r=0.16,P<0.01);消极应对维度分量表得分与HAMD-24得分成正相关(r=0.18,P<0.01)、与HAMA-14得分成正相关(r=0.23,P<0.01)、与SSRS成负相关(r=-0.18,P<0.01)。模型适配良好(2/df=1.71,RMSEA=0.07,GFI=0.87,CFI=0.91,IFI=0.91,TLI=0.90)、聚敛效度达标(AVE=0.43/0.38,CR=0.90/0.78)、区分效度理想(两维度间具有显著的相关性,但相关性系数小于0.5,且小于AVE的平方根)。结论适当修订后的SCSQ在女性UI患者中信效度良好,可以用于女性UI患者应对方式的评估。

101例胎儿性染色体非整倍体异常核型分布特征及妊娠结局分析

目的分析101例胎儿性染色体非整倍体(sex chromosome aneuploidy,SCA)异常核型分布特征及妊娠结局。方法回顾性收集2016年1月~2021年12月7821例于广西壮族自治区人民医院成功进行产前核型诊断孕妇的临床资料,均行细胞培养染色体核型分析与拷贝数变异测序(copy number variation sequencing,CNV-seq)检测,对检出的101例SCA异常胎儿病历进行分析。结果SCA共检出101例,检出率为1.29%。其中克氏综合征占比33.66%,超雌综合征占比17.82%,超雄综合征占比12.87%,特纳综合征占比10.89%,其他非整倍体异常(包括:48,XXXY 1例,69,XXY[80%]/68,XXY,-22[20%]1例)占比1.98%,嵌合体占比22.77%。101例SCA产前指征结果为:年龄≥35周岁占比53.47%(54/101),血清生化指标筛查高/临界风险占比4.95%(5/101),胎儿超声检测异常占比17.82%(18/101),无创产前基因检测(non-invasive prenatal testing,NIPT)异常占比51.49%(52/101),不良孕产史占比12.87%(13/101),其他原因(孕妇脑瘫1例、双方珠蛋白生成障碍性贫血4例)5例行产前诊断,占比4.95%(5/101),部分病例并发多项产前诊断指征。23例诊断为性染色体嵌合体的胎儿,其中有22例通过核型与CNV-seq双向验证,11例孕妇选择终止妊娠,其余选择继续妊娠。结论产前核型诊断联合血清学检测、孕期超声等不同产前筛查手段,有利于提高SCA检出率。而CNV-seq可对性染色体嵌合体孕妇的遗传咨询提供更多临床依据。

22q11.2微缺失综合征的产前诊断回顾性研究

目的 回顾性分析52例22q11.2微缺失综合征(22q11.2deletion syndrome,22q11.2DS)胎儿孕期超声及遗传学特点,探讨22q11.2DS产前可能的影像学表型特征。方法 回顾性分析2018年1月至2022年12月在云南省第一人民医院进行孕中期(孕18~26周)产前诊断为22q11.2DS的52例胎儿孕期超声、染色体核型分型及拷贝数变异检测(copy number variation,CNV)结果及遗传学特点,统计分析并随访妊娠结局。结果 (1)胎儿超声:82.7%(43/52)有异常表现,最常见的是心脏异常(65.4%,34/52)其中12例合并心外异常(12/52);心脏异常最常见的是法洛四联症、右位主动脉弓、右锁骨下动脉迷走;心外系统异常23例(23/52)出现频率:NT增厚(9/52)、肾脏异常(7/52)、鼻骨发育不良(2/52)、头颅异常(2/52)、胸腺发育不良(3/52)、胃肠道(3/52)、肢体异常(2/52)、羊水多(1/52)。(2)胎儿染色体CNVs结果:46例(46/52)CNVs缺失片段位置在:LCR22A-D18850002150004经典缺失区域,大小在2.65~2.89Mb之间;胎儿表型外显不全、表现度不一致。(3)32例(32/52)亲代溯源检查,结果提示(27/52)新发突变,8例(6个家系)系母系遗传。(4)遗传咨询:45例(45/52)要求终止妊娠;继续妊娠的7例(7/52)中4例目前情况良好,1例(母系遗传)出生后5个月心脏手术治疗,1例拒绝随访,1例发病。结论 22q11.2DS胎儿大多有超声结构异常,主要涉及心脏结构异常,心外异常主要NT增厚及肾积水;有表型胎儿CNVs缺失片段主要在LCR22A-D经典缺失区域但表型外显不全,表现度差异大。

高龄孕妇产前诊断胎儿染色体异常结果特征分析

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。

全外显子测序联合基因组拷贝数变异测序在儿科遗传病诊断中的应用

目的探讨全外显子测序(whole exome sequencing,WES)联合基因组拷贝数变异测序(copy number variation sequencing,CNVseq)在儿科遗传病诊断中的应用价值。方法选取2019年8月至2023年7月郑州市妇幼保健院新生儿科及儿科收治的怀疑患有遗传性疾病或临床诊断不明确的患儿为研究对象,采集患儿及其父母外周血进行WES及CNVseq检测,对检出的变异进行分类及评级,并进行一代测序或qPCR验证。结果共纳入患儿33例,其中男性18例,女性15例,年龄范围为1 d~8岁。WES的阳性检出率为36.4%(12/33),CNVseq阳性检出率为9.1%(3/33),两者联合阳性检出率为45.5%(15/33)。结论WES联合CNVseq是儿童遗传性疾病分子诊断的有力工具,可作为一线检测手段在临床大力推广。

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。

侵犯著作权罪与销售侵权复制品罪的冲突及教义学构建

侵犯著作权罪与销售侵权复制品罪的区分是刑事司法实践中长期存在的疑难问题。《刑法修正案(十一)》的出台在一定程度上解决了发行的“瘦身”问题,但两罪的关系依旧悬而未决。两高近期出台的《关于办理侵犯知识产权刑事案件适用法律若干问题的解释(征求意见稿)》试图再次解决这一难题,但依旧存在诸多不足之处。发行含义的界定不清导致两罪名的关系不明,引发司法实践中的适用混乱。民刑两大部门法的不同思维模式及概念体系的混用是导致这一问题的根本原因。传统理论存在方法论上的缺陷,应在法秩序统一的教义学立场上,以类型思维为工具,准确描述发行的类型,将两罪定位为法条竞合关系并从一重罪适用,同时杜绝数罪并罚的做法,体系性地消除适用冲突。