• Title/Summary/Keyword: Chromosomal translocation

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Outcome of Preimplantation Genetic Diagnosis for Chromosome Aneuploidy and Genetic Disease (유전질환 및 염색체 이상의 예방을 위한 착상전 유전진단의 결과)

  • Kim, Jin-Yeong;Lim, Chun-Kyu;Song, In-Ok;Yoo, Keun-Jai;Yang, Kwang-Moon;Han, Kuk-Sun;Hur, Kuol;Song, Ji-Hong;Jun, Jin-Hyun;Min, Dong-Mi;Park, So-Yeon;Jun, Jong-Young;Koong, Mi-Kyoung;Kang, Inn-Soo
    • 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.

Different Responses to Arsenic Trioxide between NB4 and UF-1, Acute Promyelocytic Leukemia Cell Lines (급성 전골수성 백혈병 세포주간의 삼산화비소에 대한 반응)

  • Kim, Hye-Ran;Choi, Yoon-Jeong;Ryu, Seong-Yeoll;Lee, Young-Seok;Lee, Sang-Hwa
    • Journal of Life Science
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    • v.16 no.5
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    • pp.759-766
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    • 2006
  • Acute promyelocytic leukemia (APL) is a myeloid leukemia caused by over-expression of fusion protein, PML/RAR$({\alpha})$, which was the result of chromosomal translocation and induces the blockage of differentiation of affected promyelocytes. Pharmacological dose of retinoic acid induces the activation of and subsequent degradation of PML/RAR$({\alpha})$ fusion protein, and then APL cells undergo through the normal differentiation pathway. Arsenic trioxide has proved effective in causing remission of acute promyelocytic leukemia by inducing apoptosis of this tumor cells, whereas the heterogeneity of cellular susceptibility to this cytotoxic agent limited its usage on more types of tumors in clinic. This work showed that arsenic trioxide could induce apoptosis of a panel of acute promyelocytic leukemic cell lines, all-trans-retinoic acid (ATRA) sensitive NB4 cells and ATRA resistant UF-1 cell. They were investigated with regard to the correlation between the inherent or intrinsic cellular level of GSH and the apoptotic susceptibility of the cells to arsenic trioxide. We manifested, in two cell types, the inherently existed difference in intracellular GSH level reactive to the arsenic trioxide, and a positive correlation between the GSH level and their apoptotic sensitivity to arsenic trioxide. And it showed that arsenic trioxide could differentiate promyelocytic cancer cells to the cells possessed of dendritic cell surface markers. Unravelling the cause of the different susceptibility between leukemic cells and proving that promyelocyte could be differentiated to dendritic cells by arsenic trioxide will help not only to understand the mechanism underlying the complete remission of acute promyelocytic leukemia induced by arsenic trioxide, but also to expand its clinical usage.

Assessment of DNA damage and Chromosome aberration in human lymphocyte exposed to low dose radiation detected by FISH(fluorescence in situ hybridization) and SCGE(single cell gel electrophoresis) (FISH기법 및 단세포전기영동기법을 이용한 저선량 방사선에 의한 DNA 상해 및 염색체이상 평가)

  • Chung, Hai-Won;Kim, Su-Young;Kim, Byung-Mo;Kim, Sun-Jin;Kim, Tae-Hwan;Cho, Chul-Koo;Ha, Sung-Whan
    • Journal of Radiation Protection and Research
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    • v.25 no.4
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    • pp.223-232
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    • 2000
  • Comparative study was performed for the assessment of DNA damage and Chromosomal aberration in human lymphocyte exposed to low dose radiation using fluorescence in situ hybridization(FISH) and single cell gel electrophoresis(SCGE). Chromosomal aberrations in human lymphocytes exposed to radiation at doses of 5, 10, 30 and 50cGy were analysed with whole chromosome-specific probes by human chromosome 1, 2 and 4 according to PAINT system. FISH with chromosome-specific probe has been used to be a valid and rapid method fer detection of chromosome rearrangements induced by low dose radiation. The frequencies of stable translocation per cell equivalents were 0.0116, 0.0375, 0.040f, 0.0727 and 0.0814 for 0, 5, 10, 30 and 50cGy, respectively, and those of dicentric were 0.00, 0.0125, 0.174, 0.0291 and 0.0407 respectively. Radiation induced DNA damage in human lymphocyte in a dose-dependent manner at low doses from 5cGy to 50cGy, which were analysed by single tell gel electrophoresis(SCGE). From above results, FISH seemed to be useful for radiation biodosimetry by which the frequencies of stable aberrations in human lymphocyte can be observed more easily than by conventional method and SCGE also seemed to be sensitive method f9r detecting DNA damage by low dose radiation exposure, so that those methods will improve our technique to perform meaningful biodosimetry for radiation at low doses.

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Studies on the Biological Effects of Chemosterilant, Hempa, on the Rice Weevil (Sitophilus oryzae 1.) and Transmission of Sterility (화학적 불임유기물질 Hempa가 쌀바구미(Sitophilus oryzae L.)에 미치는 생물학적 영향 및 불임성의 전달에 관한 연구)

  • Shim Jai Wook
    • Korean journal of applied entomology
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    • v.12 no.1
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    • pp.1-21
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    • 1973
  • Some experiments were conducted to investigate the effects of the chemosterilant, hempa, on the biology of the rice weevil, Sitophilus oryzae L., and the transmission of the lethal factors in the progeny. One to three days old adult males were fed on the wheat grains treated with concentrations of 0.0625, 0.125, 0.25, and $0.5\%$ of hempa water solution. The effects of the treatment on the mortality, longevity, and the performance of oviposition were examined for the Pl generation, and the hatchability and mortality in the postembryonic development were also tested in the $F_1,\;F_2,\;BC_1,\;F_3,\;and\;BC_2$ generations to analyze the inheritance of the lethal factors. The results obtained were summarized as follows. (1) The average longevity of the treated males were ranged from 26.6 to 30.4 days, and indicated no statistical differences. (2) The mortality of the treated males were ranged between $3.3\%\;and\;13.3\%$ and showed no statistical significance. (3) The overall mean number of eggs laid by a female mated to a treated male with concentrations of 0.0625, 0.125, 0.26 and $0.5\%$ were 3.78, 4.05, 3.75 and 3.61 for the respective treatments, and they were not differ significantly from those of control which were 3.60 per female per 3 day period. The unmated female laid 1.91 in the same period, and significantly differ from those in other experimental groups. (4) The overall mean hatchability of the eggs laid by the females mated with males that had been treated with various concentrations of hempa were 86.82, 64.77, 53.47, 40.33 and $24.78\%$ for the respective concentrations of 0, 0.0625, 0.125, 0.25 and $0.5\%$. The hatchability decreased with the increasing concentrations. (5) The minimum hatchabilities were obtained from the eggs laid in the period of 10-12 days after treatment, then the hatchability increased showing some recovery. The recovery seemed to be very much delayed for the males which had been treated with the greater concentrations. Such a difference in hatchability might be related with the sensitivity of the developmental stages of the sperms, and broader spectrum in the stages and severer effects seemed to be associated with the increased concentrations. (6) The overall mean of larval mortality in the $F_l$ generation were 6.55, 17.89, 27.40, 35.42 and $52.17\%$ for the respective concentrations of 0,0.0625, 0.125,0.25 and $0.5\%$. And there was a tendency to increase in the mortality with the increase of concentrations. (7) The correlation coefficients between per cent sterile eggs and larval mortality for the experimental plots of 0.125, 0.25 and $0.5\%$ treatments showed r=+0.83 and +0.85, respectively, and it seemed to be close correlation between the lethal effects on the embryonic and post-embryonic developments. (8) Since the $SC_{50}$ of the sterile eggs was $0.133\%$ and $SC_{50}$ of the larval mortality was $0.565\%$, it was considered that tile lethal factors expressed more in the egg stages than the larval stages. (9) The ratio of female to male in the $F_l$ adults showed 100 : 125, 100 : 108 and 100 : 124 for the plots of 0.125, 0.25 and $0.5\%$ treatments, respectively. And it n·as considered that the sex ratio distortions might occur with the higher concentrations. (10) When the F, males originated 1.on the eggs had been laid by p, in the period of 16-18 days after treatment, were crossed to normal females $(BC_1)$ and made sib matings $(F_2)$, the per cent sterile eggs of the $BC_1$ generation were 13.88 and $33.04\%$ , and were 31.01 and $38.73\%$ for the $F_2$generation with the plots of 0.0625 and $0.125\%$ treatment, respectively. And these seemed to be a results of the $F_1$ individuals are carrying some chromosomal aberrations (11) The larval mortality was the highest in the $F_2$ plot and followed the female backcross plot, and the least in the male backcrosses. (12) The proportions of 1st and 2nd instar larvae among the larval development at tile 17th day after oviposition were 10.98, 27.26, 32.98 and $15.73\%$ in the normal female $\times$ normal male, $F_1$ female$\times$normal male, normal $female \;\times F_1$ male and $female \;\times F_1$ male plots, respectively. It was considered that the larval development might be delayed by the treatment in the 2nd generation. (13) Per cent larval mortality and sterile eggs were greater in the $F_2$ sib mating plots $(F_3)$ than both of $F_2$ backcrosses. Therefore, it seemed that some of the recessive lethal mutations might affect in the further generations. (14) The sterility, induced by the treatment of chemosterilant, hempa, was considered as the result of the dominant lethal mutations due to chromosomal aberrations such as translocation and/or deletion. The effects of these lethal factors seemed to be inherited tip to 3rd generation after treatment.

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