• YAKHAK HOEJI
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• v.22 no.4
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• pp.175-192
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• 1978

Chlorination of the polluted water may produce odoriferous and objectionable-tasting chlorophenols which are hazardous to health. These studies were undertaken to investigate the hazardous effects of chlorophenols to the rat. 1. The chlorophenols such as o-chlorophenol and 2,6-dichlorophenol inhibited rat growth and caused increment of the ratio between liver weight and body weight. 2. The hemoglobin content, hamatocrit ratio and A/G of rat blood were decreased by chlorophenols administration. The activities of alkaline phosphatase, lactic dehydrogenase (LDH) and glutamate oxaloacetate transaminase (GOT) in serum as well as in liver were increased provisonally and decreased after one or two weeks adminstration. 3. The liver mitochondrial respiration ($QO_{2}$) was inhibited by chlorophenols treatment in in-vivo and in-vitro test. 4. The liver microsomal cytochrome P-450 was decreased by chlorophenols administration 5. Liver tissue was degenerated with congestion, atrophy, swelling, vacuolation, dilation of rough endoplasmic reticulum and denature of mitochondrial particle with swelling, and cristal destruction by chlorophenols adminstration. 6. After one and two weeks of adminstration of chlorophenols to rat, the aberrations of bone marrow chromosome and inhibition of its mitosis were observed respectively.

• Journal of Genetic Medicine
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• v.11 no.2
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• pp.49-55
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• 2014

Genetic ultrasonography refers to the evaluation of risk of chromosomal abnormalities via various soft sonographic markers. Although the maternal serum test is the primary screening method for chromosomal abnormalities, genetic ultrasonography is also widely used and can help increase detection rates. To date, many soft markers, including choroid plexus cysts, echogenic intracardiac foci, mild ventriculomegaly, nuchal fold thickening, echogenic bowel, mild pyelectasis, short femur and humerus length, and absent or hypoplastic nasal bone, have been reported. An aberrant right subclavian artery was the most novel soft marker introduced. Because these soft markers involve diverse relative risks of chromosomal abnormalities, it is difficult to apply them to clinical practice. To optimize the efficacy of genetic ultrasonography, it is important to understand the precise relative risks of chromosomal abnormalities innumerous soft markers and integrate these risks with each other and the results of maternal serum screening.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.8
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• pp.1103-1108
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• 2008

An investigation to determine frequency and distribution of folate sensitive chromosomal fragile sites was carried out in a Pakistani breed of Lohi sheep to uncover fragile site phenomena. The means and standard errors of aberrant cell count (AC) and Number of aberrations (NoA) in Lohi sheep were $0.56{\pm}0.15$ and $0.59{\pm}0.16$ in the control cultures. FUdR treated cells showed significantly higher (p<0.001) AC and NoA means ($2.18{\pm}0.33$ and $2.65{\pm}0.50$). The sex comparison for the frequency of expression indicated that males had significantly higher number of aberrant cells and total number of aberrations in FUdR cultures than the female group in Lohi sheep. The comparison of control cultures was however, not significantly different between the two groups. The regression analysis of FUdR-induced chromosomal fragility data analysis of the fragility data predicted very low ${\beta}$ of 0.325 and 0.412 for AC and NoA respectively. Lohi chromosomes expressed lesions in only 7 and 24 bands in the control and FUdR cultures respectively. The total number of significantly fragile bands in the Lohi genome was only 4. The X-chromosome of the Lohi sheep was highly stable at $5{\mu}g/ml$ FUdR with no fragile sites. The sex comparison for the distribution of fragile sites across the Lohi genome did not reveal any noticeable differences.

• Journal of Genetic Medicine
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• v.7 no.2
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• pp.111-118
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• 2010

Chromosomal microarray analysis (CMA) enables the genome-wide detection of submicroscopic chromosomal imbalances with greater precision and accuracy. In most other countries, CMA is now a commonly used clinical diagnostic test, replacing conventional cytogenetics or targeted detection such as FISH or PCR-based methods. Recently, some consensus statements have proposed utilization of CMA as a first-line test in patients with multiple congenital anomalies not specific to a well-delineated genetic syndrome, developmental delay/intellectual disability, or autism spectrum disorders. CMA can be used as an adjunct to conventional cytogenetics to identify chromosomal abnormalities observed in G-banding analysis in constitutional or acquired cases, leading to a more accurate and comprehensive assessment of chromosomal aberrations. Although CMA has distinct advantages, there are several limitations, including its inability to detect balanced chromosomal rearrangements and low-level mosaicism, its interpretation of copy number variants of uncertain clinical significance, and significantly higher costs. For these reasons, CMA is not currently a replacement for conventional cytogenetics in prenatal diagnosis. In clinical applications of CMA, knowledge and experience based on genetics and cytogenetics are required for data analysis and interpretation, and appropriate follow-up with genetic counseling is recommended.

• 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).

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7129-7138
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• 2015

Background: The polycystic ovary syndrome (PCOS), characterized by hyperandrogenism and chronic anovulation, is a common endocrine disorder in women. PCOS, which is associated with polycystic ovaries, hirsutism, obesity and insulin resistance, is a leading cause of female infertility. In this condition there is an imbalance in female sex hormones. All the sequelae symptoms of PCOS gradually lead to cancer in the course of time. It is heterogeneous disorder of unknown etiology so it is essential to find the exact cause. Materials and Methods: In this study both invasive and non-invasive techniques were employed to establish the etiology. Diagnosis was based on Rotterdam criteria (hyperandrogenism, ovulatory dysfunction, PCOM) and multiparameters using buccal samples and dermatoglypic analysis and cytogenetic study for 10 cases and four age and sex matched controls. Results: In clinical analysis we have observed the mean value of total testosterone level was 23.6nmol/L, total hirsutism score was from 12-24, facial acne was found in in 70% patients with 7-12 subcapsular follicular cysts, each measuring 2-8 mm in diameter. In dermatoglypic analysis we observed increases in mean value ($45.9^{\circ}$) of ATD angle when compared with control group and also found increased frequency (38%) of Ulnar loops on both fingers (UU), (18%) whorls on the right finger and Ulnar loop on left finger (WU) and (16%) arches on right and left fingers (AA) were observed in PCOS patients when compared with control subjects. Features which could be applied as markers for PCOS patients are the presence of Ulnar loops in middle and little fingers of right and left hand. The buccal micronucleus cytome assay in exfoliated buccal cells, we found decrease in frequency of micronuclei and significant increases in frequency of karyolysed nuclei in polycystic ovarian syndrome patients. Chromosome aberration analysis revealed a significant increase in frequency of chromosome aberrations (CAs) in PCOS patients when compared with controls. Conclusions: From this present work it can be concluded that non-invasive technique like dermatoglypics analysis and buccal micronucleus cytome assays with exfoliated buccal cell can also be effective biomarkers for PCOS, along with increased CAs in lymphocytes as a sign of genetic instability. There is a hypothesis that micronuclei and chromosomal aberrations could have a predictive value for cancer. From this present work it can be concluded to some extent that non-invasive technique like dermatoglypics and buccal cell analysis can also be effective for diagnosis.

• Korean Journal of Head & Neck Oncology
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• v.24 no.1
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• pp.33-42
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• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9495-9498
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• 2014

Background: The difference in prognosis of adult and childhood acute lymphoblastic leukemia (ALL) can be attributed largely to variation in cytogenetic abnormalities with age groups. Cytogenetic analysis in acute leukemia is now routinely used to assist patient management, particularly in terms of diagnosis, disease monitoring, prognosis and risk stratification. Knowing about cytogenetic profile at the time of diagnosis is important in order to take critical decisions in management of the patients. Aim and Objectives: To determine the frequency of cytogenetic abnormalities in Pakistani adult patients with ALL in order to have insights regarding behavior of the disease. Materials and Methods: A retrospective analysis of all the cases of ALL (${\geq}15$years old) diagnosed at Aga Khan University from January 2006 to June 2014 was performed. Phenotype (B/T lineage) was confirmed in all cases by flow cytometry. Cytogenetic analysis was made for all cases using the trypsin-Giemsa banding technique. Karyotypes were interpreted using the International System for Human Cytogenetic Nomenclature (ISCN) criteria. Results: A total of 166 patients were diagnosed as ALL during the study period, of which 151 samples successfully yielded metaphase chromosomes. The male to female ratio was 3.4:1. The majority (n=120, 72.3%) had a B-cell phenotype. A normal karyotype was present in 51% (n=77) of the cases whereas 49% (n=74) had an abnormal karyotype. Of the abnormal cases, 10% showed Philadelphia chromosome; t(9;22)(q34;q11.2). Other poor prognostic cytogenetic subgroups were t(4;11)(q21;q23), hypodiploidy (35-45 chromosomes) and complex karyotype. Hyperdiploidy (47-57 chromosomes) occurred in 6.6%; all of whom were younger than 30 years. Conclusions: This study showed a relatively low prevalence of Philadelphia chromosome in Pakistani adults with ALL with an increase in frequency with age (p=0.003). The cumulative prevalence of Philadelphianegative poor cytogenetic aberrations in different age groups was not significant (p=0.6).

• Journal of Genetic Medicine
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• v.12 no.2
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• pp.118-122
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• 2015

Noninvasive prenatal test (NIPT) is a novel screening method for the diagnosis of fetal chromosomal aneuploidies. NIPT is based on technology that detects cell-free fetal DNA in maternal plasma and analyzes it with massively parallel sequencing technology to determine whether the fetus is at risk of trisomy 21, trisomy 18, trisomy 13 or sex chromosome abnormalities (SCAs). NIPT has been reported to have sensitivity of 99% and a false positive rate of less than 1% for detecting trisomy 21 and trisomy 18. Although extension of the application of NIPT to other SCAs has been attempted, there are concerns in extending NIPT to SCAs because of maternal or fetal mosaicism, undetected maternal SCAs, and multiple pregnancies. Recently, we assessed a pregnancy with the rare Turner syndrome mosaicism 45, X/47, XXX, which was reported as 45, X with NIPT. We present the case here and briefly review the current literatures on NIPT in testing for fetal monosomy X. To the best of our knowledge, this is the first report of the 45, X/47, XXX mosaicism in Korea to be reported as 45, X by NIPT with whole genome sequencing. This case report will provide valuable information for counseling women who want to undergo NIPT.

• Journal of Genetic Medicine
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• v.16 no.1
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• pp.10-14
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• 2019

Purpose: The aim of this study was to investigate the clinicopathological features of premature ovarian insufficiency (POI) associated with chromosomal abnormalities. Materials and Methods: This was a retrospective study of POI patients with chromosomal abnormalities diagnosed between January 2009 and December 2017. The definition of POI is based on hypergonadotropinism of 40 or greater in follicle stimulating hormone (FSH) measurements at age 40 years or less. FSH was measured twice at least 4 weeks apart. Karyotyping using peripheral blood for chromosomal testing was conducted in all patients diagnosed with POI. We analyzed the clinical characteristics and genetic causes of patients who were diagnosed with POI. Results: Forty patients were diagnosed with POI including 9 (22.5%) with identified chromosomal abnormalities. The mean age at diagnosis was $23.1{\pm}7.8years$ (ranging between 14 and 39). Three patients did not experience menarche. The presenting complaints were short stature in one case, one case of amenorrhea with ambiguous external genitals, one case of infertility, and six related to menstruation such as oligomenorrhea or irregular rhythm. Turner syndrome was diagnosed in four cases, Xq deletion in one case, trisomy X in two cases, and 46,XY disorder of sexual development in two other patients. Conclusion: Patients diagnosed with POI carrying the same type of chromosomal abnormality manifest different phenotypes. The management protocol also needs to be changed depending on the diagnosis. A karyotype is indicated for accurate diagnosis and proper management of POI in patients, with or without stigmata of chromosomal abnormalities.