Genomic polymorphisms come in various forms including single nucleotide variations, translocations, insertions and copy number variations (CNVs). As a form of structural variation, the CNVs comprise common and rare forms based on their populational frequencies. Studies have demonstrated that certain CNVs are associated with risks for neuro-developmental diseases, viral infections, chronic inflammations, and cancers. With the development of high-resolution genome typing technologies such as microarrays and whole genome sequencing, the human genomic CNVs map has been continuously improved and refined. In-depth study of CNVs not only can provide comprehensive understanding for their structural variations and genetic evolution, but also provide new insights into genetic factors contributing to such diseases. In this paper, the general characteristics, pathogenesis and detection methods for the CNVs, as well as their association with human diseases are reviewed.
DNA Copy Number Variations ; Genetic Predisposition to Disease ; Humans

OBJECTIVETo investigate the genome copy number variation (CNV) related with keloid using the whole-gene resequencing technology.

METHODSA keloid pedigree containing 4 generation of 27 people was studied. Five people (4 cases of keloid patients, and 1 case of normal) were selected to extract the genomic DNA. Then the whole-gene resequencing technique was used to check the variations based on the Illumina Hiseq 2000.

RESULTSThrough database comparison and variation annotation analysis, 15 CNVs associated with scar hyperplasia were obtained. DAVID software was used to do the Gene Ontology and pathway analysis. Five CNVs were closely related to the keloid formation. They were growth factor receptor-bound 7 (Grb7), mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), mitogen-activated protein kinase kinase kinase 15 (MAP3K15), kruppel-like factors 7 (KLF7) and NK2 homeobox 2 (NKX2-2). These CNVs were involved in the process of epidermal cells formation and differentiation, cell exocrine and cell adhesion.

CONCLUSIONSThere are 5 CNVs associated with scar hyperplasia. Especially MAP3K15 and MAP4K4 deserve more research to find their function in keloid formation.

Copy number variation (CNV) is an important type of genomic structural variation and plays a crucial role in genomic disorders imposed by diseases. Most of the current bioinformatic researches focus on developing algorithms and tools for detecting CNVs from single or paired datasets, but the analysis of such CNVs is not sufficient from a family-based genetic point of view. We performed a trio-sample family based parents-offspring CNV analysis using the 1000G data. We found a number of CNVs that the offsprings inherited from their parents and inferred through hierarchical analysis how they were generated. In addition, we also discovered several de novo CNV candidates.
Algorithms ; Computational Biology ; DNA Copy Number Variations ; Genomics ; Humans

OBJECTIVE: To analyze the clinical phenotype and genetic variant of a child with Snijders Blok-Campeau syndrome (SBCS). METHODS: A child who was diagnosed with SBCS in June 2017 at Henan Children's Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and the extraction of genomic DNA, which was subjected to trio-whole exome sequencing (trio-WES) and genome copy number variation (CNV) analysis. Candidate variant was verified by Sanger sequencing of his pedigree members. RESULTS: The main clinical manifestations of the child have included language delay, intellectual impairment and motor development delay, which were accompanied with facial dysmorphisms (broad forehead, inverted triangular face, sparse eyebrows, widely spaced eyes, narrow palpebral fissures, broad nose bridge, midface hypoplasia, thin upper lip, pointed jaw, low-set ears and posteriorly rotated ears). Trio-WES and Sanger sequencing revealed that the child has harbored a heterozygous splicing variant of the CHD3 gene, namely c.4073-2A>G, for which both of his parents were of wild-type. No pathogenic variant was identified by CNV testing. CONCLUSION The c.4073-2A>G splicing variant of the CHD3 gene probably underlay the SBCS in this patient.
DNA Copy Number Variations ; Heterozygote ; Pedigree ; Phenotype ; RNA Splicing ; Mutation

Neonatal screening is one of the crucial parts of the tertiary prevention strategy to reduce congenital disability. Traditional neonatal screening, mainly focusing on genetic metabolic diseases, has limitations in disease types and requires genetic testing for further validation and accurate typing. Currently, conducting genetic screening based on biochemical metabolite screening has become the trend in neonatal screening. This article synthesizes the current state of neonatal genome screening at home and abroad. Herein, the comprehensive concepts of "SNV Plus" (single nucleotide variation plus) and "CNV Plus" (copy number variation plus) have been proposed to develop a new technology that can detect the gene structure of SNV and CNV simultaneously and improve the level of neonatal genome screening based on characteristics of the pathogenic gene structure.
DNA Copy Number Variations ; Humans ; Infant, Newborn ; Neonatal Screening ; Nucleotides

DNA Copy Number Variations ; Heart Defects, Congenital/genetics* ; Humans

Recently, researches on copy number variation （CNV） have extended to every field, such as etiological exploration and precise treatment of complex diseases, as well as genetic breeding and evolution. The unique genetic characteristics of CNV have made people gradually believe that it could be used as a biological genetic marker to solve related problems. With the development of detection technology, application of CNV in forensic medicine will increase gradually. In this paper, the concept and development of CNV, as well as its application in forensic medicine are summarized, to provide new ideas for the practical application of CNV in the future.
DNA Copy Number Variations ; Forensic Medicine ; Genetic Markers

DNA Copy Number Variations ; Epilepsy ; genetics ; Genetic Variation ; Humans ; Sequence Analysis, DNA

OBJECTIVE: To assess the value of next-generation sequencing-based copy number variation sequencing (CNV-seq) for the detection of copy number variations (CNVs) in prenatal diagnosis. METHODS: The results of single nucleotide polymorphism array (SNP-array) for prenatal diagnosis from May 2018 to December 2020 were reviewed. Selected cases of CNVs of clinical significance or low-percentage mosaic aneuploidies were included. Preserved DNA samples of amniotic fluid DNA were detected by CNV-seq. The results of CNV-seq and CMA were analyzed. RESULTS: A total of 16 488 data of SNP-array were re-analyzed, and 343 DNA samples were selected for the CNV-seq assay. All samples were successfully analyzed. Compared with the SNP-array, the proportion of full concordance, partial concordance and missed detection was 91.5% (314/343), 1.2% (4/343) and 7.3% (25/343), respectively. The non-detection zones of CNV-seq were confirmed, which have encompassed the SHOX gene and AZFc region. CONCLUSION With a high accuracy and wide genome-wide coverage, CNV-seq is worthy for a wide application in prenatal diagnosis, though the limitation of testing should be taken into consideration, and the appropriate prenatal diagnosis method should be selected for different populations to reduce the occurrence of birth defects.
Aneuploidy ; DNA ; DNA Copy Number Variations ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Pregnancy ; Prenatal Diagnosis/methods*

Objective: To investigate the association between peripheral blood mitochondrial DNA copy number (mtDNAcn) and incident risk of liver cancer. Methods: At the baseline of Dongfeng-Tongji (DFTJ) cohort, 27 009 retirees were recruited from Dongfeng Motor Corporation in 2008. After excluding people without baseline DNA, with current malignant tumor and loss of follow-up, 1 173 participants were randomly selected into a sub-cohort by age-and gender-stratified sampling method at a proportion of 5% among all retirees. A total of 154 incident liver cancer cases identified from the cohort before December 31, 2018 (4 cases had been selected into the sub-cohort) were selected to form the case cohort of liver cancer. For the above 1 323 participants, their baseline levels of mtDNAcn in peripheral blood cells were measured by using quantitative real-time PCR method. The restricted cubic spline analysis was used to fit the shape of the association between baseline mtDNAcn and incident risk of liver cancer. The weighted Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95%CI. Results: In this case-cohort study, the median follow-up time was 10.3 years. The restricted cubic spline analysis indicated that the relationship between peripheral blood mtDNAcn and incident risk of liver cancer followed a U-shaped pattern (P_non-linear<0.05). All case-cohort population were divided into four subgroups by sex-specific quartiles of mtDNAcn levels among sub-cohort participants, when compared to participants in the Q₂ subgroup of mtDNAcn, those in the Q₁ subgroup (HR=2.00,95%CI:1.08-3.70) and Q₄ subgroup (HR=4.11,95%CI:2.32-7.26) both had a significantly elevated risk of liver cancer, while those in the Q₃ subgroup (HR=1.05,95%CI:0.54-2.05) had not. There were no significant multiply interaction effects of aging, gender, tobacco smoking, alcohol drinking and history of chronic hepatitis on the above association (P_interaction>0.05). Conclusion: Both extremely low and high baseline level of mtDNAcn in peripheral blood cells are associated with an increased risk of incident liver cancer, but the underlying mechanisms need to be further clarified.
Cohort Studies ; DNA Copy Number Variations ; DNA, Mitochondrial/genetics* ; Female ; Humans ; Liver Neoplasms/genetics* ; Male ; Mitochondria