• Clinical and Experimental Reproductive Medicine
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• v.38 no.3
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• pp.126-134
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• 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.

• Journal of Genetic Medicine
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• v.12 no.2
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• pp.123-127
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• 2015

Distal limb deformities are congenital malformations with phenotypic variability and high genetic heterogeneity. Split hand/foot malformation, also known as ectrodactyly, is a congenital limb malformation characterized by a defect of the central rays of the hands and/or feet. Split hand/foot malformation with long-bone deficiency (SHFLD) is a rare condition related to a 17p13.3 duplication. Recently, genomic duplications encompassing BHLHA9 have been associated with SHFLD. We report a case of SHFLD presenting with campomelia of the right femur, bilateral agenesis of fibulae, bilateral club feet, and oligosyndactyly of the hands and feet, that was associated with a 17p13.3 duplication, as determined prenatally using array comparative genomic hybridization.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.4
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• pp.310-316
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• 2020

Microarray technology represents a critical new advance in molecular cytogenetics. The development of this approach has provided fundamental insights into the molecular pathogenesis in clinical cytogenetics and has provided a clue to many unidentified or unexplained diseases. The approach allows a comprehensive investigation of thousands and millions of genomic loci simultaneously and enables the efficient detection of copy number alterations. The application of this technology has shown tremendous fluidity and complexity of the human genome, and has provided accurate diagnosis and appropriate clinical management in a timely and efficient manner for identifying genomic alterations. The clinical impact of the genomic alterations identified by microarrays is evolving into a diagnostic tool to identify high-risk patients better and predict patient outcomes from their genomic profiles. The transformation of conventional cytogenetics into an automated discipline will improve diagnostic yield significantly, leading to accurate diagnosis and genetic counseling. This article reviews cytogenetic technologies used to identify human chromosome alterations and highlights the potential utility of present and future genome microarray technology in the diagnosis.

• Clinical and Experimental Reproductive Medicine
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• v.39 no.2
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• pp.52-57
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• 2012

Objective: During IVF, non-transferred embryos are usually selected for cryopreservation on the basis of morphological criteria. This investigation evaluated an application for array comparative genomic hybridization (aCGH) in assessment of surplus embryos prior to cryopreservation. Methods: First-time IVF patients undergoing elective single embryo transfer and having at least one extra non-transferred embryo suitable for cryopreservation were offered enrollment in the study. Patients were randomized into two groups: Patients in group A (n=55) had embryos assessed first by morphology and then by aCGH, performed on cells obtained from trophectoderm biopsy on post-fertilization d5. Only euploid embryos were designated for cryopreservation. Patients in group B (n=48) had embryos assessed by morphology alone, with only good morphology embryos considered suitable for cryopreservation. Results: Among biopsied embryos in group A (n=425), euploidy was confirmed in 226 (53.1%). After fresh single embryo transfer, 64 (28.3%) surplus euploid embryos were cryopreserved for 51 patients (92.7%). In group B, 389 good morphology blastocysts were identified and a single top quality blastocyst was selected for fresh transfer. All group B patients (48/48) had at least one blastocyst remaining for cryopreservation. A total of 157 (40.4%) blastocysts were frozen in this group, a significantly larger proportion than was cryopreserved in group A (p=0.017, by chi-squared analysis). Conclusion: While aCGH and subsequent frozen embryo transfer are currently used to screen embryos, this is the first investigation to quantify the impact of aCGH specifically on embryo cryopreservation. Incorporation of aCGH screening significantly reduced the total number of cryopreserved blastocysts compared to when suitability for freezing was determined by morphology only. IVF patients should be counseled that the benefits of aCGH screening will likely come at the cost of sharply limiting the number of surplus embryos available for cryopreservation.

• Genomics & Informatics
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• v.5 no.3
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• pp.137-139
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• 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).

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2001.10b
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• pp.190-190
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• 2001

• Journal of Life Science
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• v.19 no.4
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• pp.449-456
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• 2009

Murine Neuro-2a (N2a) cells have been widely used for the investigation of neuronal differentiation, trophic interaction and neurotoxic effects of various compounds and their associated mechanisms. N2a cells have many genomic variations such as gains or losses in DNA copy number, similar to other neuroblastoma cells, and no systematic or high-resolution studies of their genome-wide chromosomal aberrations have been reported. Presently, we conducted a systematic genome-wide determination of chromosomal aberrations in N2a cells using a high-throughput, oligonucleotide array-based comparative genomic hybridization (oaCGH) technique. A hidden Markov Model was employed to assign each genomic oligonucleotide to a DNA copy number state: double loss, single loss, normal, gain, double gain and amplification. Unlike most neuroblastoma cells, Mycn amplification was not observed in N2a cells. In addition, these cells showed gain only in the neuron-derived neurotrophic factor (NF), while other neurotrophic factors such as glial line-derived NF and brain-derived NF presented normal copy numbers. Chromosomes 4, 8, 10, 11 and 15 displayed more than 1000 aberrational oligonucleotides, while chromosomes 3, 17, 18 and 19 displayed less than 20. The largest region of gain was located on chromosome 8 and its size was no less than 26.7 Mb (Chr8:8427841-35162415), while chromosome 4 had the longest region of single deletion, with a size of 15.1 Mb (Chr4:73265785-88374165).

• Journal of Gastric Cancer
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• v.12 no.2
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• pp.73-80
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• 2012

Purpose: The specific aim of this study is to unravel a DNA copy number alterations, and to search for novel genes that are associated with the development of Korean gastric cancer. Materials and Methods: We investigated a DNA copy number changes in 23 gastric adenocarcinomas by array-comparative genomic hybridization and quantitative real-time polymerase chain reaction analyses. Besides, the expression of UQCRFS1, which shows amplification in array-CGH, was examined in 186 gastric cancer tissues by an immunohistochemistry, and in 9 gastric cancer cell lines, as well as 24 gastric cancer tissues by immunoblotting. Results: We found common gains at 48 different loci, and a common loss at 19 different loci. Amplification of UQCRFS1 gene at 19q12 was found in 5 (21.7%) of the 23 gastric cancers in an array-comparative genomic hybridization and DNA copy number were increased in 5 (20.0%) out of the 25 gastric cancer in quantitative real-time polymerase chain reaction. In immunohistochemistry, the overexpression of the protein was detected in 105 (56.5%) out of the 186 gastric cancer tissues. Statistically, there was no significant relationship between the overexpression of UQCRFS1 and clinicopathologic parameters (P>0.05). In parallel, the overexpression of UQCRFS1 protein was confirmed in 6 (66.7%) of the 9 gastric cancer cell lines, and 12 (50.0%) of the 24 gastric cancer tissues by immunoblotting. Conclusions: These results suggest that the overexpression of UQCRFS1 gene may contribute to the development and/or progression of gastric cancer, and further supported that mitochondrial change may serve as a potential cancer biomarker.

• Journal of Interdisciplinary Genomics
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• v.2 no.1
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• pp.10-12
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• 2020

Coffin-Lowry syndrome (CLS) is a genetic disorder characterized by intellectual disability, typical facial features, and skeletal abnormalities. But this syndrome shows highly variable clinical manifestations, and can't be diagnosed with conventional chromosome analysis or comparative genomic hybridization, leading to delayed diagnosis. Here we report an 18-year-old boy with CLS diagnosed by whole exome sequencing. Our patient initially presented with developmental delay, facial dysmorphism at the age of 1. At the age of 18, he developed orthopnea due to mitral regurgitation. At the 22 years of age, he was diagnosed as CLS diagnosed by whole exome sequencing. Our case implies that clinical suspicion is important for early diagnosis, and advanced diagnostic tools such as WES should be considered in suspected cases.

• Proceedings of the IEEK Conference
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• 2008.06a
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• pp.897-898
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• 2008

Array comparative genomic hybridization (aCGH) has been used to detect chromosomal regions of amplifications or deletions, which allows identification of new cancer related genes. As aCGH, a large-scale spatial data, contains significant amount of noises in its raw data, it has been an important research issue to segment genomic DNA regions to detect its true underlying copy number aberrations (CNAs). In this study, we focus on applying a segmentation method to multiple data sets. We compare two different threshold values for analyzing aCGH data with CBS method [1]. The proposed threshold values are p-value or $Q{\pm}1.5IQR$ and $Q{\pm}1.5IQR$.