• 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.

• 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.

• 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.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제30권2호
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• pp.205-212
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• 2008

인간 게놈의 DNA서열의 차이는 개개인의 특이성을 의미하기 때문에 염기서열의 변화는 질병에 대한 감수성, 약물에 대한 반응 등 개인의 성향에 큰 영향을 미치게 된다. 인간 게놈에는 여러 가지 형태의 유전적 변이가 존재하지만 그 중 단일염기다형성이 인간의 유전적, 표현형의 다양성을 설명하는 주된 유전적 변이로 생각되었으나 최근 유전체 전체 분석법의 발전으로 1 kb 이상 크기의 CNV의 발견으로 개체간의 유전적 다양성에 대한 더 많은 이해가 가능하게 되었고, 진화와 유전 질환에 대한 CNV의 역할을 조사하는 연구의 기초를 제공하게 되었다. 현재 인간게놈의 CNV를 찾아내고 특성화 작업을 목표로 하는 The Copy Number Variation Project를 위해 The Wellcome Trust Institute (Hinxton, United Kingdom), Hospital for Sick Children (Toronto), University of Tokyo (Tokyo), Affymetrix (Santa Clara, CA), 그리고 Harvard Medical School/Brigham and Women's Hospital (Boston, MA) 등이 참여하는 international consortium이 구성되어 보다 심도 있는 연구가 진행되고, 또한 향후 진보된 DNA microarray-based technology와 서열화 기술의 개발로 인간 게놈 상의 모든 유전적 변이를 발견하게 되고 포괄적인 CNV 지도를 완성하고 인간 유전자 다양성 인간의 진화, 유전적 질환 개인 맞춤형 의학에 대한 새로운 이해와 연구가 가능하게 될 것으로 기대된다.

• 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.

• 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.

• Genomics & Informatics
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• 제12권1호
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• pp.42-47
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• 2014

Asian populations contain a variety of ethnic groups that have ethnically specific genetic differences. Ethnic variants may be highly relevant in disease and human differentiation studies. Here, we identified ethnically specific variants and then investigated their distribution across Asian ethnic groups. We obtained 58,960 Pan-Asian single nucleotide polymorphisms of 1,953 individuals from 72 ethnic groups of 11 Asian countries. We selected 9,306 ethnic variant single nucleotide polymorphisms (ESNPs) and 5,167 ethnic variant copy number polymorphisms (ECNPs) using the nearest shrunken centroid method. We analyzed ESNPs and ECNPs in 3 hierarchical levels: superpopulation, subpopulation, and ethnic population. We also identified ESNP- and ECNP-related genes and their features. This study represents the first attempt to identify Asian ESNP and ECNP markers, which can be used to identify genetic differences and predict disease susceptibility and drug effectiveness in Asian ethnic populations.

• 정보처리학회논문지D
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• 제16D권5호
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• pp.661-672
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• 2009

인간의 유전체 서열에는 유전체 단위반복변위(copy number variation, CNV)를 포함하는 다양한 유전적 구조 변이(genetic structural variation)가 존재하며, 이는 기능적으로 질병에 대한 감수성, 치료에 대한 반응, 유전적 특성 등과 밀접한 관련이 있다. 본 논문에서는 기가 시퀀싱(giga sequencing)의 결과 산출되는 대량의 짧은 길이의 DNA 서열 데이터를 이용한 새로운 CNV 검색 방식을 제안한다. 제안하는 알고리즘에서는 레퍼런스 시퀀스에 DNA 서열 데이터를 서열 정렬시켜 각 레퍼런스 시퀀스의 위치에 대한 서열 데이터의 출현 빈도 정보를 얻은 후, 출현 빈도 정보의 패턴을 분석하여 통계적 유의성을 갖는 1kbp 이상의 연속 영역을 CNV 후보 영역으로 추출한다. 또한 제안된 알고리즘을 효율적으로 지원하기 위한 서열 정렬 방식에 대한 비교 및 분석을 수행한다. 제안된 기법의 유용성을 규명하기 위하여 다양한 실험을 수행하였다. 실험 결과에 의하면, 제안된 기법은 비교적 낮은 커버리지의 기가 시퀀싱 데이터를 이용하여 반복되거나 결실되는 다양한 형태의 CNV 영역을 효율적으로 검출하며, 또한 작은 사이즈의 CNV 영역에서부터 큰 사이즈의 CNV 영역까지 다양한 크기의 CNV 영역을 효율적으로 검출 할 수 있는 것으로 나타났다.

• Genomics & Informatics
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• 제14권4호
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• pp.216-221
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• 2016

Osteoporotic fractures (OFs) are critical hard outcomes of osteoporosis and are characterized by decreased bone strength induced by low bone density and microarchitectural deterioration in bone tissue. Most OFs cause acute pain, hospitalization, immobilization, and slow recovery in patients and are associated with increased mortality. A variety of genetic studies have suggested associations of genetic variants with the risk of OF. Genome-wide association studies have reported various single-nucleotide polymorphisms and copy number variations (CNVs) in European and Asian populations. To identify CNV regions associated with OF risk, we conducted a genome-wide CNV study in a Korean population. We performed logistic regression analyses in 1,537 Korean subjects (299 OF cases and 1,238 healthy controls) and identified a total of 8 CNV regions significantly associated with OF (p < 0.05). Then, one CNV region located on chromosome 20q13.12 was selected for experimental validation. The selected CNV region was experimentally validated by quantitative polymerase chain reaction. The CNV region of chromosome 20q13.12 is positioned upstream of a family of long non-coding RNAs, LINC01260. Our findings could provide new information on the genetic factors associated with the risk of OF.

• 한국작물학회:학술대회논문집
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• 한국작물학회 1999년도 춘계 학술대회지
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• pp.162-163
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• 1999

The goal of this research was (1) to describe the conditions and parameters required for the cell cycle synchronization and the accumulation of large number of metaphase cells in maize and other cereal root tips, (2) to isolate intact metaphase chromosomes from root tips suitable for characterization by flow cytometry, and (3) to construct chromosome-specific libraries from maize. Plant metaphase chromosomes have been successfully synchronized and isolated from many cereal root-tips. DNA synthesis inhibitor (hydroxyurea) was used to synchronize cell cycle, follwed by treatement with trifluralin to accumulate metaphase chromosomes. Maize flow karyotypes show substantial variation among inbred lines. thish variation should be sueful in isolating individual chromosome types. In addition, flow cytometry is a useful method to measure DNA content of individual chromosomes in a genotyps, and to detect chromosomal variations. Individual chromosome peaks have been sorted from the maize hybrid B73/Mol7. Libraries were generated form the DOP-PCR amplification product from each peak. To date, we have analyzed clones from a library constructed from the maize chromosome 1 peak. Hybridization of labeled genomic DNA to clone inserts indicated that $24\%,\;18\%,\;and\;58\%$ of the clones were highly repetitive, medium repetitive, and low copy, respectively. Fifty percent of putative low cpoy clones showed single bands on inbred screening, blots, and the remaining $50\%$ were low copy repeats. Single copy clones showing polymorphism will be mapped using recombinant inbred mapping populations. Repetitive clones are being characterized by Southern blot analysis, and will be screened by in situ hybridization for their potential utility as chromosome specific markers.