• Journal of Chest Surgery
• /
• 제44권2호
• /
• pp.123-130
• /
• 2011

Background: The aim of the present study was to identify chromosomal loci that contribute to the pathogenesis of aortic dissection (AD) in a Korean population using array comparative genomic hybridization (CGH) and to confirm the results using real-time polymerase chain reaction (PCR). Materials and Methods: Eighteen patients with ADs were enrolled in this study. Genomic DNA was extracted from individual blood samples, and array CGH analyses were performed. Four corresponding genes with obvious genomic changes were analyzed using real-time PCR in order to assess the level of genomic imbalance identified by array CGH. Results: Genomic gains were most frequently detected at 8q24.3 (56%), followed by regions 7q35, 11q12.2, and 15q25.2 (50%). Genomic losses were most frequently observed at 4q35.2 (56%). Real-time PCR confirmed the results of the array CGH studies of the COL6A2, DGCR14, PCSK6, and SDHA genes. Conclusion: This is the first study to identify candidate regions by array CGH in patients with ADs. The identification of genes that may predispose an individual to AD may lead to a better understanding of the mechanism of AD formation. Further multicenter studies comparing cohorts of patients of different ethnicities are warranted.

• Genomics & Informatics
• /
• 제5권3호
• /
• pp.137-139
• /
• 2007

RAN-aCGH is an R GUI tool for the analysis and visualization of array comparative genomic hybridization (array-CGH) experiments. The tool consists of data-loading, preprocessing for missing data, several methods for statistical identification of DNA copy number aberration, and visualization of the copy number change. RAN-aCGH requires a single input format, provides various visualizations, and allows the addition of a new statistical method, all in a user-friendly graphic user interface (GUI).

• Journal of Genetic Medicine
• /
• 제8권1호
• /
• pp.62-66
• /
• 2011

14q32.33을 포함한 14번 염색체 장완 결실은 드문 질환이다. 14번 염색체의 말단 결실은 여러 임상증상을 공통적으로 보일 수 있으나 결실 절단부 (breakpoint)에 따라 표현형이 다양하게 발생할 수 있다. 저자들은 경련을 동반한 5세 여아에서 array comparative genomic hybridization (array-CGH)와 fluorescence in situ hybridization (FISH) 방법을 이용하여 이전 보고에 비해 가장 작은 14q32.33부위의 0.33 Mb 크기의 말단 결실과 심하지 않은 표현형을 보이는 1례를 경험 하였기에 문헌고찰과 함께 보고하는 바이다.

• Clinical and Experimental Pediatrics
• /
• 제60권9호
• /
• pp.282-289
• /
• 2017

Purpose: Recent advancements in molecular techniques have greatly contributed to the discovery of genetic causes of unexplained developmental delay. Here, we describe the results of array comparative genomic hybridization (CGH) and the clinical features of 27 patients with global developmental delay. Methods: We included 27 children who fulfilled the following criteria: Korean children under 6 years with global developmental delay; children who had at least one or more physical or neurological problem other than global developmental delay; and patients in whom both array CGH and G-banded karyotyping tests were performed. Results: Fifteen male and 12 female patients with a mean age of $29.3{\pm}17.6months$ were included. The most common physical and neurological abnormalities were facial dysmorphism (n=16), epilepsy (n=7), and hypotonia (n=7). Pathogenic copy number variation results were observed in 4 patients (14.8%): 18.73 Mb dup(2)(p24.2p25.3) and 1.62 Mb del(20p13) (patient 1); 22.31 Mb dup(2) (p22.3p25.1) and 4.01 Mb dup(2)(p21p22.1) (patient 2); 12.08 Mb del(4)(q22.1q24) (patient 3); and 1.19 Mb del(1)(q21.1) (patient 4). One patient (3.7%) displayed a variant of uncertain significance. Four patients (14.8%) displayed discordance between G-banded karyotyping and array CGH results. Among patients with normal array CGH results, 4 (16%) revealed brain anomalies such as schizencephaly and hydranencephaly. One patient was diagnosed with Rett syndrome and one with $M{\ddot{o}}bius$ syndrome. Conclusion: As chromosomal microarray can elucidate the cause of previously unexplained developmental delay, it should be considered as a first-tier cytogenetic diagnostic test for children with unexplained developmental delay.

• Molecular & Cellular Toxicology
• /
• 제4권3호
• /
• pp.246-252
• /
• 2008

Tumor tissue is usually contaminated by normal tissue components, which reduces the sensitivity of analysis for exploring genetic alterations. Although microdissection has been adopted to minimize the contamination of tumor DNA with normal cell components, there is a concern over the amount of microdissected DNA not enough to be applied to array-CGH reaction. To amplify the extracted DNA, several whole genome amplification (WGA) methods have been developed, but objective comparison of the array-CGH outputs using different types of WGA methods is still scarce. In this study, we compared the performance of non-amplified microdissected DNA and DNA amplified in 2 WGA methods such as degenerative oligonucleotide primed (DOP)-PCR, and multiple strand displacement amplification (MDA) using Phi 29 DNA polymerase. Genomic DNA was also used to make a comparison. We applied those 4 DNAs to whole genome BAC array to compare the false positive detection rate (FPDR) and sensitivity in detecting copy number alterations under the same hybridization condition. As a result microdissected DNA method showed the lowest FPDR and the highest sensitivity. Among WGA methods, DOP-PCR amplified DNA showed better sensitivity but similar FPDR to MDA-amplified method. These results demonstrate the advantage and applicability of microdissection for array-CGH analysis, and provide useful information for choosing amplification methods to study copy number alterations, especially based on precancerous and microscopically invaded lesions.

• Journal of Genetic Medicine
• /
• 제10권1호
• /
• pp.52-56
• /
• 2013

Mosaic trisomy 14 syndrome is a well-known but unusual chromosomal abnormality with a distinct and recognizable phenotype. Array comparative genomic hybridization (CGH) analysis has recently become a widely used method for detecting DNA copy number changes, in place of traditional karyotype analysis. However, the array CGH shows a limitation for detecting the low-level mosaicism. Here, we report the detailed clinical and cytogenetic findings of patient with low-frequency mosaic trisomy 14, initially considered normal based on usual cut-off levels of array CGH, but confirmed by G-banding karyotyping. Our patient had global developmental delay, short stature, congenital heart disease, craniofacial dysmorphic features, and dark skin patches over her whole body. Estimated mosaicism proportion was 23.3% by G-banding karyotyping and 18.0% by array CGH.

• Molecules and Cells
• /
• 제24권1호
• /
• pp.105-112
• /
• 2007

Most neuroblastoma cells have chromosomal aberrations such as gains, losses, amplifications and deletions of DNA. Conventional approaches like fluorescence in situ hybridization (FISH) or metaphase comparative genomic hybridization (CGH) can detect chromosomal aberrations, but their resolution is low. In this study we used array-based comparative genomic hybridization to identify the chromosomal aberrations in human neuroblastoma SH-SY5Y cells. The DNA microarray consisting of 4000 bacterial artificial chromosome (BAC) clones was able to detect chromosomal regions with aberrations. The SH-SY5Y cells showed chromosomal gains in 1q12~ q44 (Chr1:142188905-246084832), 7 (over the whole chro-mosome), 2p25.3~p16.3 (Chr2:18179-47899074), and 17q 21.32~q25.3 (Chr17:42153031-78607159), while chromosomal losses detected were the distal deletion of 1p36.33 (Chr1:552910-563807), 14q21.1~q21.3 (Chr14:37666271-47282550), and 22q13.1~q13.2 (Chr22:36885764-4190 7123). Except for the gain in 17q21 and the loss in 1p36, the other regions of gain or loss in SH-SY5Y cells were newly identified.

• 대한두경부종양학회지
• /
• 제24권2호
• /
• pp.155-161
• /
• 2008

Head and neck squamous cell carcinoma(HNSCC) still has poor outcome, and laryngeal cancer is the most frequent subtype of HNSCC. Therefore, there is a need to develop novel treatments to improve the outcome of patients with HNSCC. It is critical to gain further understanding on the molecular and chromosomal alteration of HNSCC to identify novel therapeutic targets but genetic etiology of squamous cell carcinoma of the larynx is so complex that target genes have not yet been clearly identified. Array based CGH(array-CGH) allows investigation of general changes in target oncogenes and tumor suppressor genes, which should, in turn, lead to a better understanding of the cancer process. In this study, We used genomic wide array-CGH in tissue specimens to map genomic alterations found in laryngeal squamous cell carcinomas. As results, gains of MAP2, EPHA3, EVI1, LOC389174, NAALADL2, USP47, CTDP1, MASP1, AHRR, and KCNQ5, with losses of SRRM1L, ANKRD19, FLJ39303, ZNF141, DSCAM, GPR27, PROK2, ARPP-21, and B3GAT1 were observed frequently in laryngeal squamous cell carcinoma tissue specimens. These data about the patterns of genomic alterations could be a basic step for understanding more detailed genetic events in the carcinogenesis and also provide information for diagnosis and treatment in laryngeal squamous cell carcinoma. The high resolution of array-CGH combined with human genome database would give a chance to find out possible target genes which were gained or lost clones.

• 대한두경부종양학회지
• /
• 제24권1호
• /
• pp.33-42
• /
• 2008

Head and neck squamous cell carcinoma(HNSCC) is notorious for its poor outcome and increasing incidence. But, the studies of cytogenetic analysis in HNSCC are relatively rare, because of difficulties in culturing solid tumor cells and complexity in chromosomal DNA abberations associated with the lesions. The purpose of this study is to evaluate the location of chromosomal aberrations in Korean HNSCC cell lines (SNU-1041, 1066, and 1076) with comparative genomic hybridization(CGH) and array based CGH(array-CGH). Chromosomal gains of 3q23-q27, 5p13-p15.3, 7p21-pter, 8q11.2-q12, 8q21.1-qter, 9q22-q34, 16q22-q24, and 20q11.2-qter, as well as chromosomal losses on 3p10-p14 were found in all 3 SNU cell lines. Losses on 3p15- p23, 4q22-q27, 4q31.3-qter, 6q14-q15, 7q31-q34, 8p12-pter, 18q21-q23, and 21q11.2-q12 were observed in 2 of 3 cell lines. In array-CGH, many genes were altered including gains of PIK3CA, MYC, EVI1, MAD1L1 genes and losses of SERPIN genes. These aberrations of gene and chromosome coincide with other results of study, generally. These data about the patterns of chromosomal aberrations could be a basic step for understanding more detailed genetic events in the carcinogenesis and also provide information for diagosis and treatment in HNSCC.

• Clinical and Experimental Reproductive Medicine
• /
• 제38권3호
• /
• pp.126-134
• /
• 2011

Preimplantation genetic diagnosis (PGD) is gradually widely used in prevention of gene diseases and chromosomal abnormalities. Much improvement has been achieved in biopsy technique and molecular diagnosis. Blastocyst biopsy can increase diagnostic accuracy and reduce allele dropout. It is cost-effective and currently plays an important role. Whole genome amplification permits subsequent individual detection of multiple gene loci and screening all 23 pairs of chromosomes. For PGD of chromosomal translocation, fluorescence $in-situ$ hybridization (FISH) is traditionally used, but with technical difficulty. Array comparative genomic hybridization (CGH) can detect translocation and 23 pairs of chromosomes that may replace FISH. Single nucleotide polymorphisms array with haplotyping can further distinguish between normal chromosomes and balanced translocation. PGD may shorten time to conceive and reduce miscarriage for patients with chromosomal translocation. PGD has a potential value for mitochondrial diseases. Preimplantation genetic haplotyping has been applied for unknown mutation sites of single gene disease. Preimplantation genetic screening (PGS) using limited FISH probes in the cleavage-stage embryo did not increase live birth rates for patients with advanced maternal age, unexplained recurrent abortions, and repeated implantation failure. Polar body and blastocyst biopsy may circumvent the problem of mosaicism. PGS using blastocyst biopsy and array CGH is encouraging and merit further studies. Cryopreservation of biopsied blastocysts instead of fresh transfer permits sufficient time for transportation and genetic analysis. Cryopreservation of embryos may avoid ovarian hyperstimulation syndrome and possible suboptimal endometrium.