• Genomics & Informatics
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• 제12권4호
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• pp.136-144
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• 2014

Besides single-nucleotide variants in the human genome, large-scale genomic variants, such as copy number variations (CNVs), are being increasingly discovered as a genetic source of human diversity and the pathogenic factors of diseases. Recent experimental findings have shed light on the links between different genome architectures and CNV mutagenesis. In this review, we summarize various genomic features and discuss their contributions to CNV formation. Genomic repeats, including both low-copy and high-copy repeats, play important roles in CNV instability, which was initially known as DNA recombination events. Furthermore, it has been found that human genomic repeats can also induce DNA replication errors and consequently result in CNV mutations. Some recent studies showed that DNA replication timing, which reflects the high-order information of genomic organization, is involved in human CNV mutations. Our review highlights that genome architecture, from DNA sequence to high-order genomic organization, is an important molecular factor in CNV mutagenesis and human genomic instability.

• Genomics & Informatics
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• 제10권1호
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• pp.65-67
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• 2012

We have discovered copy number variations (CNVs) in 3,578 Korean individuals with the Affymetrix Genome-Wide SNP array 5.0, and 4,003 copy number variation regions (CNVRs) were defined in a previous study. To explore the details of the variants easily in related studies, we built a database, cataloging the CNVs and related information. This system helps researchers browsing these variants with gene and structure variant annotations. Users can easily find specific regions with search options and verify them from system-integrated genome browsers with annotations.

• Journal of Genetic Medicine
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• 제20권2호
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• pp.46-51
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• 2023

Exonic copy number variation (CNV), involving deletions and duplications at the gene's exon level, presents challenges in detection due to their variable impact on gene function. The study delves into the complexities of identifying large CNVs and investigates less familiar but recurrent exonic CNVs, notably enriched in East Asian populations. Examining specific cases like DRC1, STX16, LAMA2, and CFTR highlights the clinical implications and prevalence of exonic CNVs in diverse populations. The review addresses diagnostic challenges, particularly for single exon alterations, advocating for a strategic, multi-method approach. Diagnostic methods, including multiplex ligation-dependent probe amplification, droplet digital PCR, and CNV screening using next-generation sequencing data, are discussed, with whole genome sequencing emerging as a powerful tool. The study underscores the crucial role of ethnic considerations in understanding specific CNV prevalence and ongoing efforts to unravel subtle variations. The ultimate goal is to advance rare disease diagnosis and treatment through ethnically-specific therapeutic interventions.

• Genomics & Informatics
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• 제6권1호
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• pp.1-7
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• 2008

The widespread presence of large-scale genomic variations, termed copy number variation (CNVs), has been recently recognized in phenotypically normal individuals. Judging by the growing number of reports on CNVs, it is now evident that these variants contribute significantly to genetic diversity in the human genome. Like single nucleotide polymorphisms (SNPs), CNVs are expected to serve as potential biomarkers for disease susceptibility or drug responses. However, the technical and practical concerns still remain to be tackled. In this review, we examine the current status of CNV DBs and research, including the ongoing efforts of CNV screening in the human genome. We also discuss the characteristics of platforms that are available at the moment and suggest the potential of CNVs in clinical research and application.

• Animal cells and systems
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• 제15권4호
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• pp.301-309
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• 2011

Charcot-Marie-Tooth disease (CMT) is clinically heterogeneous hereditary motor and sensory neuropathies with genetic heterogeneity, age-dependent penetrance, and variable expressivity. Rare copy number variations by nonrecurrent rearrangements have recently been suggested to be associated with Charcot-Marie-Tooth 1A (CMT1A) neuropathy. In our previous study, we found three Korean CMT1A families with rare copy number variations (CNVs) on 17p12 by nonrecurrent rearrangement. Careful clinical examinations were performed in all the affected individuals with rare CNVs (n=19), which may be the first full study of a subject from a large CMT1A family with nonrecurrent rearrangement. The clinical phenotype showed no significant difference compared with common CMT1A patients, but with variable phenotypes. In particular, a broad intrafamilial phenotypic spectrum was observed within the same family, which may suggest the existence of a genetic modifier. This study may broaden the understanding of the role of CNVs in the pathogenesis of CMT.

• 응용통계연구
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• 제24권5호
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• pp.847-859
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• 2011

cDNA microarray-based comparative genomic hybridization(CGH) data includes low-intensity spots and thus a statistical strategy is needed to detect subtle differences between different cancer classes. In this study, genes displaying a high frequency of alteration in one of the different classes were selected among the pre-selected genes that show relatively large variations between genes compared to total variations. Utilizing copy-number changes of the selected genes, this study suggests a statistical approach to predict patients' classes with increased performance by pre-classifying patients with similar genetic alteration scores. Two-stage logistic regression model(TLRM) was suggested to pre-classify homogeneous patients and predict patients' classes for cancer prediction; a decision tree(DT) was combined with logistic regression on the set of informative genes. TLRM was constructed in cDNA microarray-based CGH data from the Cancer Metastasis Research Center(CMRC) at Yonsei University; it predicted the patients' clinical diagnoses with perfect matches (except for one patient among the high-risk and low-risk classified patients where the performance of predictions is critical due to the high sensitivity and specificity requirements for clinical treatments. Accuracy validated by leave-one-out cross-validation(LOOCV) was 83.3% while other classification methods of CART and DT performed as comparisons showed worse performances than TLRM.

• Communications for Statistical Applications and Methods
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• 제16권6호
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• pp.1037-1046
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• 2009

Copy number variations(CNVs) are known as one of the most important factors in susceptibility to genetic disorders because they affect expression levels of genes. In previous studies, pyrosequencing, mini-sequencing real-time polymerase chain reaction(PCR), invader assays and other techniques have been used to detect CNVs. However, the higher the copy number in a genome, the more difficult it is to resolve the copies, so a more accurate method for measuring CNVs and assigning genotype is needed. PCR followed by a quantitative oligonucleotide ligation assay(qOLA) was developed for quantifying CNVs. The aim of this study was to compare the two methods for detecting and quantifying the CNVs of duplicated gene: the published pyrosequencing assay(pyro_CNV) and the newly developed qOLA_CNV. The accuracy and precision of the assay were evaluated for porcine KIT, which was selected as a model locus. Overall, the root mean squares(RMSs) of bias and standard deviation of qOLA_CNV were 2.09 and 0.45, respectively. These values are less than half of those of pyro CNV.

• Genomics & Informatics
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• 제18권1호
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• pp.3.1-3.8
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• 2020

Patient-derived xenograft (PDX) mouse models are frequently used to test the drug efficacy in diverse types of cancer. They are known to recapitulate the patient characteristics faithfully, but a systematic survey with a large number of cases is yet missing in lung cancer. Here we report the comparison of genomic characters between mouse and patient tumor tissues in lung cancer based on exome sequencing data. We established PDX mouse models for 132 lung cancer patients and performed whole exome sequencing for trio samples of tumor-normal-xenograft tissues. Then we computed the somatic mutations and copy number variations, which were used to compare the PDX and patient tumor tissues. Genomic and histological conclusions for validity of PDX models agreed in most cases, but we observed eight (~7%) discordant cases. We further examined the changes in mutations and copy number alterations in PDX model production and passage processes, which highlighted the clonal evolution in PDX mouse models. Our study shows that the genomic characterization plays complementary roles to the histological examination in cancer studies utilizing PDX mouse models.

• Journal of Genetic Medicine
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• 제18권1호
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• pp.31-37
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• 2021

Purpose: To summarize the results of chromosomal microarray analysis (CMA) for copy number variants (CNVs) detection and clinical utility in a single tertiary hospital. Materials and Methods: We performed CMA in 46 patients over the course of two years. Detected CNVs were classified into five categories according to the American College of Medical Genetics and Genomics guidelines and correlated with clinical manifestations. Results: A total of 31 CNVs were detected in 19 patients, with a median CNV number per patient of two CNVs. Among these, 16 CNVs were classified as pathogenic (n=3) or likely pathogenic (LP) (n=11) or variant of uncertain significance (n=4). The 16p11.2 deletion and 16p13.11 deletion classified as LP were most often detected in 6.5% (3/46), retrospectively. CMA diagnostic yield was 24.3% (9/37 patients) for symptomatic patients. The CNVs results of the commercial newborn screening test using next generation sequencing platforms showed high concordance with CMA results. Conclusion: CMA seems useful as a first-tier test for developmental delay with or without congenital anomalies. However, the classification and interpretation of CMA still remained a challenge. Further research is needed for evidence-based interpretation.

• 한국가금학회지
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• 제41권4호
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• pp.305-311
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• 2014

복제수변이(Copy number variation, CNV)는 DNA 다양한 구조적 변화의 한 형태이다. 복제수변이는 인간의 질병 및 농업의 생산성에 영향을 미치는 것으로 알려져 있다. 이전 우리나라의 닭의 품종은 유럽에서 유입되어진 품종을 기반으로 구축되어져 있었다. 따라서 농촌진흥청 국립축산과학원에서는 20년 동안 재래품종을 복원하려고 노력하였고, 5품종 12계통으로 복원하였다. 최근 염기서열분석 기술의 발달로, 해상도가 좋은 게놈 전체의 복제수변이를 발굴할 수 있게 되었다. 그러나 한국 재래닭 품종에 대해서는 체계적인 연구가 이루어지지 않고 있다. 본 연구에서는 한국 재래 닭(계통 L)에 대해서 게놈 전체의 염기서열을 분석하고 닭의 참고서열과 비교하여 재래닭에서 확인된 복제수 변이를 보고하였다. 닭의 28개 염색체에서 총 501개의 복제수 변이를 확인하였고, 이를 Gain과 Loss로 나누어서 표시하였다. 또한 우리는 501개의 복제수 변이를 포함하고 있는 유전자의 기능을 분류하였다. 그 결과, 전사 및 유전자 조절에 관련된 유전자들이 많이 분류되었다. 본 연구의 결과는 복제수 변이와 한국 재래닭의 경제형질 간의 연관성을 설명할 수 있는 기초자료로 활용될 것으로 사료된다.