• Molecules and Cells
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• v.37 no.10
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• pp.713-718
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• 2014

Alteration in chromosome numbers and structures instigate and foster massive genetic instability. As Boveri has seen a hundred years ago (Boveri, 1914; 2008), aneuploidy is hall-mark of many cancers. However, whether aneuploidy is the cause or the result of cancer is still at debate. The molecular mechanism behind aneuploidy includes the chromosome mis-segregation in mitosis by the compromise of spindle assembly checkpoint (SAC). SAC is an elaborate network of proteins, which monitor that all chromosomes are bipolarly attached with the spindles. Therefore, the weakening of the SAC is the major reason for chromosome number instability, while complete compromise of SAC results in detrimental death, exemplified in natural abortion in embryonic stage. Here, I will review on the recent progress on the understanding of chromosome missegregation and cancer, based on the comparison of different mouse models of BubR1, the core component of SAC.

• Journal of Radiation Protection and Research
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• v.29 no.4
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• pp.243-249
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• 2004

The cytokinesis-block micronucleus (CBMN) assay in combination with FISH technique using chromosome-specific centromeric probes for chromosome 1 and 4 was performed in mitogen stimulated human lymphocytes which were exposed to x-radiation to identify different sensitivity of chromosomes to the induction of micronuclei(MN) and aneuploidy by radiation. The frequencies of micronucleated cytokinesis-blocked(MNCB) cells and MN in binucleated lymphocytes(BN) increased with the increase in radiation dose. A significant induction of aneuploidy of chromosome 1 and 4 were found. The frequency of aneuploidy of chromosome 1 and 4 in the control were 9 per 2,000 BN cells and this increased to 47 and 71 following irradiation at a dose of 1 and 2 Gy, respectively. The induction of aneuploidy of chromosome 1 was higher than that of chromosome 4. The frequency of aneuploid BN cells with MN exhibiting positive centromere signal for either chromosome 1 and/or 4 increased in a dose dependent manner, and that for chromosome 1 is higher than that for chromosome 4. Among the total induced MN in irradiated lymphocytes, smaller proportion of MN exhibit centromeric signal of chromosome indicating that radiation-induced MN are mainly originated from chromosomal breakage rather than chromosomal non-disjunction. These results suggest that x-radiation can induce aneuploidy and supports the finding that chromosome vary in their sensitivity to aneuploidy induction by x-irradiation.

• Environmental Mutagens and Carcinogens
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• v.22 no.2
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• pp.90-96
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• 2002

Benzene is a widespread human carcinogen, inducing leukemia and hematotoxicity. Exposure to benzene metabolites has been shown to cause genetic damage, including aneusomy and chromosome aberrations. Fluorescence in situ hybridization(FISH) procedure was used to determine if the benzene metabolite, 1, 2, 4-benzenetriol(BT), hydroquinone(HQ) and trans, trans-muconic acid(t,t-MA) induced specific chromosomal change in HL-60 cells. Treatment with BT, HQ and t,t-MA resulted in the induction of monosomy 8 and 21 in HL-60 cells in a dose-dependent manner. All of these metabolites also induced trisomy 8 and 21, but no correlation between frequencies of trisomy and concentration was found. Translocations between chromosome 8 and another unidentified chromosome ［t(8:\ulcorner)］, and between chromosome 21 and another unidentified chromosome ［t(8:21)］ were found. However, translocation between chromosome 8 and 21 ［t(8:21)］ was not found. Results indicate that the benzene metabolites, BT, HQ and t,t-MA, induce chromosome specific numerical and structural aberrations, and the fluorescence in situ hybridization (FISH) approach may be a useful and powerful technique for detection of aneuploidy.

• Clinical and Experimental Reproductive Medicine
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• v.29 no.4
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• pp.269-278
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• 2002

Objective s: Chromosome aneuploidy is associated with recurrent abortion and congenital anomaly and genetic diseases occur repeatedly in the specific families. Preimplantation genetic diagnosis (PGD) can prevent aneuploidy or genetic disease by selecting normal embryos before implantation and is an alternative to prenatal diagnosis. The aim of this study is to assess the outcome of PGD cycles by using FISH or PCR, and to determine the clinical usefulness and values in patients with risk of chromosomal aneuploidy or genetic disease. Materials and Methods: From 1995 to Apr. 2001, a total of 108 PGD cycles in 65 patients with poor reproductive outcome were analyzed. The indications of PGD were translocation (n=49), inversion (n=2), aneuploidy screening (n=7), Duchenne muscular dystrophy (n=5) and spinal muscular atrophy (n=2). PGD was applied due to the history of recurrent abortion, previous birth of affected child or risk of aneuploidy related to sex chromosome aneuploidy or old age. Blastomere biopsy was performed in 6$\sim$10 cell stage embryo after IVF with ICSI. In the single blastomere, chromosome aneuploidy was diagnosed by using FISH and PCR was performed for the diagnosis of exon deletion in DMD or SMA. Results: The FISH or PCR amplification was successful in 94.3% of biopsied blastomeres. The rate of transferable balanced emb ryos was 24.0% in the chromosome translocation and inversion, 57.1% for the DMD and SMA, and 28.8% for the aneuploidy screening. Overall hCG positive rate per transfer was 17.8% (18/101) and clinical pregnancy rate was 13.9% (14/101) (11 term pregnancy, 3 abortion, and 4 biochemical pregnancy). The clinical pregnancy rate of translocation and inversion was 12.9% (11/85) and abortion rate was 27.3% (3/11). In the DMD and SMA, the clinical pregnancy rate was 33.3% (3/9) and all delivered at term. The PGD results were confirmed by amniocentesis and were correct. When the embryos developed to compaction or morula, the pregnancy rate was higher (32%) than that of the cases without compaction (7.2%, p<0.01). Conclusions: PGD by using FISH or PCR is useful to get n ormal pregnancy by reducing spontaneous abortion associated with chromosome aneuploidy in the patients with structural chromosome aberration or risk of aneuploidy and can prevent genetic disease prior to implantation.

• Journal of Genetic Medicine
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• v.12 no.2
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• pp.72-78
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• 2015

Recently, noninvasive prenatal test (NIPT) has been adopted as a primary screening tool for fetal chromosomal aneuploidy. The principle of NIPT lies in isolating the fetal fraction of cell-free DNA in maternal plasma and analyzing it with bioinformatic tools to measure the amount of gene from the target chromosome, such as chromosomes 21, 18, and 13. NIPT will contribute to decreasing the need for unnecessary invasive procedures, including amniocentesis and chorionic villi sampling, for confirming fetal aneuploidy because of its higher positive predictive value than that of the conventional prenatal screening method. However, its greater cost than that of the current antenatal screening protocol may be an obstacle to the adoption of this innovative technique in clinical practice. Digital polymerase chain reaction (dPCR) is a novel approach for detecting and quantifying nucleic acid. dPCR provides real-time diagnostic advantages with higher sensitivity, accuracy, and absolute quantification than conventional quantitative PCR. Since the groundbreaking discovery that fetal cell-free nucleic acid exists in maternal plasma was reported, dPCR has been used for the quantification of fetal DNA and for screening for fetal aneuploidy. It has been suggested that dPCR will decrease the cost by targeting specific sequences in the target chromosome, and dPCR-based noninvasive testing will facilitate progress toward the implementation of a noninvasive approach for screening for trisomy 21, 18, and 13. In this review, we highlight the principle of dPCR and discuss its future implications in clinical practice.

• Journal of Radiation Protection and Research
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• v.30 no.4
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• pp.209-219
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• 2005

This study was carried out to examine the effect of the DNA repair inhibitors, Cytosine Arabinoside(Ara C), 3-Aminobenzamide(3AB) and Hydroxyurea(HU) on the frequencies of radiation-induced micronuclei(MNi) and aneuploidy. Irradiated lymphocytes(1-3Gy) were treated with DNA repair inhibitors, Ara C, 3AB and HU for 3 hours and CBMN assay - FISH technique with DNA probe for chromosome 1 and 4 was performed. The frequencies of x-ray induced MNi and aneuploidy of chromosome 1 and 4 were increased in a dose-dependent manner. Ara C, 3AB and HU enhanced the frequencies of radiation-induced MNi and the frequencies of radiation-induced aneuploidy of chromosome 1 and 4 were enhanced by HU and Ara C while no effect was observed by 3AB. The frequency of radiation-induced aneuploidy of chromosome 1 was higher than that of chromosome 4. These results suggest that there are different mechanisms involved in the formation of MNi and aneuploidy by radiation.

• Korean Journal of Plant Taxonomy
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• v.48 no.3
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• pp.201-205
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• 2018

Carex L. (Cyperaceae) is the largest angiosperm genus in the temperate zones with more than 2,000 species worldwide. Unusual chromosome structures, called holocentric chromosomes, have been postulated to contribute to species diversity in the genus. In Korea, this genus has the greatest number of species, but chromosome information as it pertains to the taxa is mostly unknown. Here, we report meiotic chromosome numbers of five Carex taxa in Korea. The following observations are made: Carex jaluensis Kom. ($n=27_{II}$, $28_{II}$, $29_{II}$, $30_{II}$), C. japonica Thunb. ($n=28_{II}$, $29_{II}$), C. planiculmis Kom. ($n=30_{II}$), C. miyabei Franch. ($n=33_{II}$, $36_{II}$), C. neurocarpa Maxim. ($n=51_{II}$, $53_{II}$, $54_{II}$). Except for C. planiculmis, all of the species exhibit variations in chromosome numbers within individuals and/or taxa. The findings with regard to chromosome number diversity in Carex suggest that chromosome number variation (aneuploidy, agmatoploidy and/or symploidy) plays an important role in the richness of the species in the genus. Further cytological investigations are needed for a better understanding of sedge diversity in Korean flora.

• Journal of Genetic Medicine
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• v.12 no.2
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• pp.79-84
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• 2015

Purpose: We developed and validated a fetal trisomy detection method for use as a noninvasive prenatal test (NIPT) including a Clinical Laboratory Improvement Amendments (CLIA)-certified bioinformatics pipeline on a cloud-based computing system using both Illumina and Life Technology sequencing platforms for 221 Korean clinical samples. We determined the necessary proportions of the fetal fraction in the cell-free DNA (cfDNA) sample for NIPT of trisomies 13, 18, and 21 through a limit of quantification (LOQ) test. Materials and Methods: Next-generation sequencing libraries from 221 clinical samples and three positive controls were generated using Illumina and Life Technology chemistries. Sequencing results were uploaded to a cloud and mapped on the human reference genome (GRCh37/hg19) using bioinformatics tools. Based on Z-scores calculated by normalization of the mapped read counts, final aneuploidy reports were automatically generated for fetal aneuploidy determination. Results: We identified in total 29 aneuploid samples, and additional analytical methods performed to confirm the results showed that one of these was a false-positive. The LOQ test showed that the proportion of fetal fraction in the cfDNA sample would affect the interpretation of the aneuploidy results. Conclusion: Noninvasive chromosome examination (NICE), a CLIA-certified NIPT with a cloud-based bioinformatics platform, showed unambiguous success in fetus aneuploidy detection.

• Korean Journal of Ecology and Environment
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• v.42 no.2
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• pp.192-199
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• 2009

Freshwater green algae are one of the important sources of bioenergy in the future. Spirogyra is a conjugating filamentous zygnematacean green algal genus that is widely distributed worldwide with more than 400 species. Despite its widespread occurrence throughout the world, cytological studies of the genus have been limited. We investigated karyological features and chromosome numbers for seven Korean Spirogyra species. Most of the species examined in the present study showed significant karyological features, inner organization of nucleolus, heavily stainable nucleolar substance and the diffuse-centric nature of chromosomes, typical of the Conjugales. Chromosome number ranged from n=12 in S. varians to n=38 in S. africana. Aberrant cytokinesis resulted in binucleate and tetranucleate cells, which sometimes provide cytological explanation for different morphology and ploidal changes in clonal culture of Spirogyra or even different cells within the same filament. The present chromosome data also substantiates the earlier held assumption that aneuploidy must have been the chief driving force for speciation and evolution of the genus Spirogyra.

• Clinical and Experimental Reproductive Medicine
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• v.31 no.4
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• pp.253-260
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• 2004

Objectives: Klinefelter syndrome is the most common genetic cause of male infertility and presents with 47, XXY mainly or 46, XX/47, XXY mosaicism. It is characterized by hypogonadism and azoospermia due to testicular failure, however, sporadic cases of natural pregnancies have been reported. With the development of testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI), sperm can be retrieved successfully and ART is applied in these patients for pregnancy. It has been suggested that the risk of chromosome aneuploidy for both sex chromosome and autosome is increased in the sperms from 47, XXY germ cells. Considering the risk for chromosomal aneuploidy in the offspring, preimplantation genetic diagnosis (PGD) could be applied as a safe and more effective treatment option in Klinefelter syndrome. The aim of this study is to assess the outcome of PGD cycles by using FISH for sex chromosome and autosome in patients with Klinefelter syndrome. Materials and Methods: From Jan. 2001 to Dec. 2003, PGD was attempted in 8 cases of Klinefelter syndrome but TESE was failed to retrieve sperm in the 3 cases, therefore PGD was performed in 8 cycles of 5 cases (four 47, XXY and one 46, XY/47, XXY mosaicism). In one case, ejaculated sperm was used and in 4 cases, TESE sperm was used for ICSI. After fertilization, blastomere biopsy was performed in $6{\sim}7$ cell stage embryo and the chromosome aneuploidy was diagnosed by using FISH with CEP probes for chromosome X, Y and 17 or 18. Results: A total of 127 oocytes were retrieved and ICSI was performed in 113 mature oocytes. The fertilization rate was $65.3{\pm}6.0%$ (mean$\pm$SEM) and 76 embryos were obtained. Blastomere biopsy was performed in 61 developing embryos and FISH analysis was successful in 95.1% of the biopsied blastomeres (58/61). The rate of balanced embryos for chromosome X, Y and 17 or 18 was $39.7{\pm}6.9%$. The rate of aneuploidy for sex chromosome (X and Y) was $45.9{\pm}5.3%$ and $43.2{\pm}5.8%$ for chromosome 17 or 18, respectively. Embryo transfer was performed in all 8 cycles and mean number of transferred embryos was $2.5{\pm}0.5$. In 2 cases, clinical pregnancies were obtained and normal 46, XX and 46, XY karyotypes were confirmed by amniocentesis, respectively. Healthy male and female babies were delivered uneventfully at term. Conclusion: The patients with Klinefelter syndrome can benefit from ART with TESE and ICSI. Considering the risk of aneuploidy for both sex chromosome and autosome in the sperms and embryos of Klinefelter syndrome, PGD could be offered as safe and more effective treatment option.