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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳沛隆(Pei-Lung Chen) | |
| dc.contributor.author | Meng-Lin Wu | en |
| dc.contributor.author | 吳孟霖 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:09:23Z | - |
| dc.date.available | 2021-11-02 | |
| dc.date.available | 2022-11-24T03:09:23Z | - |
| dc.date.copyright | 2021-11-02 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-10-25 | |
| dc.identifier.citation | 1. Stowell, K. M. (2008). Malignant hyperthermia: a pharmacogenetic disorder. Pharmacogenomics, 9(11), 1657-1672. https://doi.org/10.2217/14622416.9.11.1657 2. Rosenberg, H., Davis, M., James, D., Pollock, N., Stowell, K. (2007). Malignant hyperthermia. Orphanet Journal of Rare Diseases, 2(1), 21. https://doi.org/10.1186/1750-1172-2-21 3. Yeh, H. M., Liao, M. H., Chu, C. L., Lin, Y. H., Sun, W. Z., Lai, L. P., Chen, P. L. (2021). Next-generation sequencing and bioinformatics to identify genetic causes of malignant hyperthermia. J Formos Med Assoc, 120(2), 883-892. https://doi.org/10.1016/j.jfma.2020.08.028 4. Schneiderbanger, D., Johannsen, S., Roewer, N., Schuster, F. (2014). Management of malignant hyperthermia: diagnosis and treatment. Therapeutics and clinical risk management, 10, 355-362. https://doi.org/10.2147/TCRM.S47632 5. Vladutiu, G. D., Isackson, P. J., Kaufman, K., Harley, J. B., Cobb, B., Christopher-Stine, L., Wortmann, R. L. (2011). Genetic risk for malignant hyperthermia in non-anesthesia-induced myopathies. Mol Genet Metab, 104(1-2), 167-173. https://doi.org/10.1016/j.ymgme.2011.07.001 6. Rosenberg, H. (2011). Continued progress in understanding the molecular genetics of malignant hyperthermia. Can J Anaesth, 58(6), 489-493. https://doi.org/10.1007/s12630-011-9495-5 7. Hirshey Dirksen, S. J., Larach, M. G., Rosenberg, H., Brandom, B. W., Parness, J., Lang, R. S., Gangadharan, M., Pezalski, T. (2011). Special article: Future directions in malignant hyperthermia research and patient care. Anesth Analg, 113(5), 1108-1119. https://doi.org/10.1213/ANE.0b013e318222af2e 8. Larach, M. G., Brandom, B., Allen, G., Gronert, G., Lehman, E. (2008). Cardiac Arrests and Deaths Associated with Malignant Hyperthermia in North America from 1987 to 2006: A Report from The North American Malignant Hyperthermia Registry of the Malignant Hyperthermia Association of the United States. Anesthesiology, 108, 603-611. 9. Sato, K., Pollock, N., Stowell, K. M. (2010). Functional studies of RYR1 mutations in the skeletal muscle ryanodine receptor using human RYR1 complementary DNA. Anesthesiology, 112(6), 1350-1354. https://doi.org/10.1097/ALN.0b013e3181d69283 10. Lanner, J. T., Georgiou, D. K., Joshi, A. D., Hamilton, S. L. (2010). Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold Spring Harb Perspect Biol, 2(11), a003996. https://doi.org/10.1101/cshperspect.a003996 11. Mungunsukh, O., Deuster, P., Muldoon, S., O'Connor, F., Sambuughin, N. (2019). Estimating prevalence of malignant hyperthermia susceptibility through population genomics data. Br J Anaesth, 123(3), e461-e463. https://doi.org/10.1016/j.bja.2019.06.010 12. Hwang, J. H., Zorzato, F., Clarke, N. F., Treves, S. (2012). Mapping domains and mutations on the skeletal muscle ryanodine receptor channel. Trends Mol Med, 18(11), 644-657. https://doi.org/10.1016/j.molmed.2012.09.006 13. Kraeva, N., Riazi, S., Loke, J., Frodis, W., Crossan, M. L., Nolan, K., Kraev, A., Maclennan, D. H. (2011). Ryanodine receptor type 1 gene mutations found in the Canadian malignant hyperthermia population. Can J Anaesth, 58(6), 504-513. https://doi.org/10.1007/s12630-011-9494-6 14. Carpenter, D., Ringrose, C., Leo, V., Morris, A., Robinson, R. L., Halsall, P. J., Hopkins, P. M., Shaw, M. A. (2009). The role of CACNA1S in predisposition to malignant hyperthermia. BMC Med Genet, 10, 104. https://doi.org/10.1186/1471-2350-10-104 15. Rosenberg, H., Pollock, N., Schiemann, A., Bulger, T., Stowell, K. (2015). Malignant hyperthermia: a review. Orphanet J Rare Dis, 10, 93. https://doi.org/10.1186/s13023-015-0310-1 16. Dulhunty, A. F., Haarmann, C. S., Green, D., Laver, D. R., Board, P. G., Casarotto, M. G. (2002). Interactions between dihydropyridine receptors and ryanodine receptors in striated muscle. Prog Biophys Mol Biol, 79(1-3), 45-75. https://doi.org/10.1016/s0079-6107(02)00013-5 17. Yeh, H. M., Tsai, M. C., Su, Y. N., Shen, R. C., Hwang, J. J., Sun, W. Z., Lai, L. P. (2005). Denaturing high performance liquid chromatography screening of ryanodine receptor type 1 gene in patients with malignant hyperthermia in Taiwan and identification of a novel mutation (Y522C). Anesth Analg, 101(5), 1401-1406. https://doi.org/10.1213/01.Ane.0000180214.74580.39 18. Kaufmann, A., Kraft, B., Michalek-Sauberer, A., Weindlmayr, M., Kress, H. G., Steinboeck, F., Weigl, L. G. (2012). Novel double and single ryanodine receptor 1 variants in two Austrian malignant hyperthermia families. Anesth Analg, 114(5), 1017-1025. https://doi.org/10.1213/ANE.0b013e31824a95ad 19. Gonsalves, S. G., Ng, D., Johnston, J. J., Teer, J. K., Stenson, P. D., Cooper, D. N., Mullikin, J. C., Biesecker, L. G. (2013). Using exome data to identify malignant hyperthermia susceptibility mutations. Anesthesiology, 119(5), 1043-1053. https://doi.org/10.1097/ALN.0b013e3182a8a8e7 20. Nagele, P. (2013). 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M. (2015). Next-generation Sequencing of RYR1 and CACNA1S in Malignant Hyperthermia and Exertional Heat Illness. Anesthesiology, 122(5), 1033-1046. https://doi.org/10.1097/aln.0000000000000610 25. Kim, J. H., Jarvik, G. P., Browning, B. L., Rajagopalan, R., Gordon, A. S., Rieder, M. J., Robertson, P. D., Nickerson, D. A., Fisher, N. A., Hopkins, P. M. (2013). Exome sequencing reveals novel rare variants in the ryanodine receptor and calcium channel genes in malignant hyperthermia families. Anesthesiology, 119(5), 1054-1065. https://doi.org/10.1097/ALN.0b013e3182a8a998 26. Urwyler, A., Deufel, T., McCarthy, T., West, S. (2001). Guidelines for molecular genetic detection of susceptibility to malignant hyperthermia. Br J Anaesth, 86(2), 283-287. https://doi.org/10.1093/bja/86.2.283 27. Hopkins, P. M., Rüffert, H., Snoeck, M. M., Girard, T., Glahn, K. P., Ellis, F. R., Müller, C. R., Urwyler, A. (2015). European Malignant Hyperthermia Group guidelines for investigation of malignant hyperthermia susceptibility. Br J Anaesth, 115(4), 531-539. https://doi.org/10.1093/bja/aev225 28. Lawal, T. A., Wires, E. S., Terry, N. L., Dowling, J. J., Todd, J. J. (2020). Preclinical model systems of ryanodine receptor 1-related myopathies and malignant hyperthermia: a comprehensive scoping review of works published 1990–2019. Orphanet Journal of Rare Diseases, 15(1), 113. https://doi.org/10.1186/s13023-020-01384-x 29. Tong, J., Oyamada, H., Demaurex, N., Grinstein, S., McCarthy, T. V., MacLennan, D. H. (1997). Caffeine and halothane sensitivity of intracellular Ca2+ release is altered by 15 calcium release channel (ryanodine receptor) mutations associated with malignant hyperthermia and/or central core disease. J Biol Chem, 272(42), 26332-26339. https://doi.org/10.1074/jbc.272.42.26332 30. Ho, S. N., Hunt, H. D., Horton, R. M., Pullen, J. K., Pease, L. R. (1989). Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene, 77(1), 51-59. https://doi.org/10.1016/0378-1119(89)90358-2 31. Zhang, T., Lin, X.-C., Tang, H., Yu, R.-Q., Jiang, J.-H. (2016). Mass spectrometry based trinucleotide repeat sequence detection using target fragment assay [10.1039/C6AY01228K]. Analytical Methods, 8(25), 5039-5044. https://doi.org/10.1039/C6AY01228K 32. Liu, Q., Zhang, P., Wang, D., Gu, W., Wang, K. (2017). Interrogating the “unsequenceable” genomic trinucleotide repeat disorders by long-read sequencing. Genome Medicine, 9(1), 65. https://doi.org/10.1186/s13073-017-0456-7 33. Park, G., Park, J. K., Shin, S. H., Jeon, H. J., Kim, N. K. D., Kim, Y. J., Shin, H. T., Lee, E., Lee, K. H., Son, D. S., Park, W. Y., Park, D. (2017). Characterization of background noise in capture-based targeted sequencing data. Genome Biol, 18(1), 136. https://doi.org/10.1186/s13059-017-1275-2 34. Pollard, T. D., Korn, E. D. (1973). Acanthamoeba myosin. I. Isolation from Acanthamoeba castellanii of an enzyme similar to muscle myosin. J Biol Chem, 248(13), 4682-4690. 35. Ellinas, H., Albrecht, M. A. (2020). Malignant Hyperthermia Update. Anesthesiol Clin, 38(1), 165-181. https://doi.org/10.1016/j.anclin.2019.10.010 36. Yang, T., Riehl, J., Esteve, E., Matthaei, K. I., Goth, S., Allen, P. D., Pessah, I. N., Lopez, J. R. (2006). Pharmacologic and functional characterization of malignant hyperthermia in the R163C RyR1 knock-in mouse. Anesthesiology, 105(6), 1164-1175. https://doi.org/10.1097/00000542-200612000-00016 37. Yang, T., Ta, T. A., Pessah, I. N., Allen, P. D. (2003). Functional defects in six ryanodine receptor isoform-1 (RyR1) mutations associated with malignant hyperthermia and their impact on skeletal excitation-contraction coupling. J Biol Chem, 278(28), 25722-25730. https://doi.org/10.1074/jbc.M302165200 38. Neuhuber, B., Huang, D. I., Daniels, M. P., Torgan, C. E. (2002). High efficiency transfection of primary skeletal muscle cells with lipid-based reagents. Muscle Nerve, 26(1), 136-140. https://doi.org/10.1002/mus.10171 39. Kreiss, P., Cameron, B., Rangara, R., Mailhe, P., Aguerre-Charriol, O., Airiau, M., Scherman, D., Crouzet, J., Pitard, B. (1999). Plasmid DNA size does not affect the physicochemical properties of lipoplexes but modulates gene transfer efficiency. Nucleic Acids Res, 27(19), 3792-3798. https://doi.org/10.1093/nar/27.19.3792 40. Stephens, J., Schiemann, A. H., Roesl, C., Miller, D., Massey, S., Pollock, N., Bulger, T., Stowell, K. (2016). Functional analysis of RYR1 variants linked to malignant hyperthermia. Temperature (Austin), 3(2), 328-339. https://doi.org/10.1080/23328940.2016.1153360 41. Merritt, A., Booms, P., Shaw, M. A., Miller, D. M., Daly, C., Bilmen, J. G., Stowell, K. M., Allen, P. D., Steele, D. S., Hopkins, P. M. (2017). Assessing the pathogenicity of RYR1 variants in malignant hyperthermia. Br J Anaesth, 118(4), 533-543. https://doi.org/10.1093/bja/aex042 42. Parker, R., Schiemann, A. H., Langton, E., Bulger, T., Pollock, N., Bjorksten, A., Gillies, R., Hutchinson, D., Roxburgh, R., Stowell, K. M. (2017). Functional Characterization of C-terminal Ryanodine Receptor 1 Variants Associated with Central Core Disease or Malignant Hyperthermia. J Neuromuscul Dis, 4(2), 147-158. https://doi.org/10.3233/jnd-170210 43. 'Entrez Gene: RYR1 ryanodine receptor 1 (skeletal)' Retrieved from https://www.ncbi.nlm.nih.gov/gene?Db=gene Cmd=ShowDetailView TermToSearch=6261 44. Gibson, D. G., Young, L., Chuang, R.-Y., Venter, J. C., Hutchison, C. A., Smith, H. O. (2009). Enzymatic assembly of DNA molecules up to several hundred kilobases. Nature Methods, 6(5), 343-345. https://doi.org/10.1038/nmeth.1318 45. Yanagida, T., Arata, T., Oosawa, F. (1985). Sliding distance of actin filament induced by a myosin crossbridge during one ATP hydrolysis cycle. 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Iosub, R., Avitabile, D., Grant, L., Tsaneva-Atanasova, K., Kennedy, H. J. (2015). Calcium-Induced calcium release during action potential firing in developing inner hair cells. Biophys J, 108(5), 1003-1012. https://doi.org/10.1016/j.bpj.2014.11.3489 52. 'Entrez Gene: CALM1 calmodulin 1 (phosphorylase kinase, delta)'. 53. Reggiani, C. (2021). Caffeine as a tool to investigate sarcoplasmic reticulum and intracellular calcium dynamics in human skeletal muscles. Journal of Muscle Research and Cell Motility, 42(2), 281-289. https://doi.org/10.1007/s10974-020-09574-7 54. Lynch, P. J., Tong, J., Lehane, M., Mallet, A., Giblin, L., Heffron, J. J., Vaughan, P., Zafra, G., MacLennan, D. H., McCarthy, T. V. (1999). A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca2+ release channel function and severe central core disease. Proc Natl Acad Sci U S A, 96(7), 4164-4169. https://doi.org/10.1073/pnas.96.7.4164 55. Tong, J., McCarthy, T. V., MacLennan, D. H. (1999). Measurement of resting cytosolic Ca2+ concentrations and Ca2+ store size in HEK-293 cells transfected with malignant hyperthermia or central core disease mutant Ca2+ release channels. J Biol Chem, 274(2), 693-702. https://doi.org/10.1074/jbc.274.2.693 56. Sambuughin, N., Nelson, T. E., Jankovic, J., Xin, C., Meissner, G., Mullakandov, M., Ji, J., Rosenberg, H., Sivakumar, K., Goldfarb, L. G. (2001). Identification and functional characterization of a novel ryanodine receptor mutation causing malignant hyperthermia in North American and South American families. Neuromuscul Disord, 11(6-7), 530-537. https://doi.org/10.1016/s0960-8966(01)00202-4 57. Oyamada, H., Oguchi, K., Saitoh, N., Yamazawa, T., Hirose, K., Kawana, Y., Wakatsuki, K., Oguchi, K., Tagami, M., Hanaoka, K., Endo, M., Iino, M. (2002). Novel mutations in C-terminal channel region of the ryanodine receptor in malignant hyperthermia patients. Jpn J Pharmacol, 88(2), 159-166. https://doi.org/10.1254/jjp.88.159 58. Smedler, E., Uhlén, P. (2014). Frequency decoding of calcium oscillations. Biochim Biophys Acta, 1840(3), 964-969. https://doi.org/10.1016/j.bbagen.2013.11.015 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80560 | - |
| dc.description.abstract | "惡性高熱症（Malignant Hyperthermia）是一種在臨床上與科學上都具有重要性的特徵性疾病，目前已知有兩個特定基因（RYR1跟CACNA1S）與至少四個基因座會導致惡性高熱症，佔總體病例中50-70%。RYR1基因則是目前所知會引起惡性高熱症最重要的基因。次世代定序（Next-generation sequencing）正徹底改變遺傳學，而我們團隊已經建立了一個以次世代定序為基礎的惡性高熱症基因檢測平台，此平台過去也幫助我們找到許多過去從未發表過的變異點，然而這些變異點的致病性依舊無法確認。 現行變異點的致病性的指南相當嚴格，在過去被報導過約300個RYR1的變異點中，只有48個被證明具有致病性，這是相當大的問題，每當我們為惡性高熱症的病人進行基因檢測後，若發現的變異點不在48個已確認的致病變異點中，我們將無法發表臨床相關報告，因此，我們迫切需要一個可靠的、經濟高效的體外RYR1功能性或致病性的測定。 先前的功能性測試是利用兔的RYR1 cDNA，而不是人類的RYR1 cDNA，且後續的細胞實驗也並非在人類的骨骼肌細胞，而是在HEK293或是從小鼠取下的肌管，然而這在科學上並不是非常令人滿意。因此，我們想要開發一種從人類RYR1 cDNA開始，並導入我們有興趣的變異點，而後於培養的人類骨骼肌細胞內進行功能性研究。 我們以Gibson assembly的方式製造含有RYR1 cDNA-IRES-H2B-mCherry-PiggyBac的表現質體。我們測試了RD與RC13這兩株人類骨骼肌細胞株的基因組DNA（genomic DNA, gDNA）以確定其RYR1與CACNA1S上沒有惡性高熱症之致病變異點。我們也針對肌肉細胞的特性對此二株細胞進行測試，我們以免疫細胞化學染色（immunocytochemical staining）來偵測肌凝蛋白與RYR1的表現，並以RT-PCR的方式偵測兩種細胞中與鈣離子相關基因的表現。我們將能表現mCherry且大小為20 kbp的質體用TransIT-X2轉染到RD與RC13。我們以流式細胞儀偵測mCherry的訊號，並將之視為轉染效率，以計算不同條件下的轉染效率。我們以咖啡因作為誘發劑來引發細胞質內鈣離子濃度變化，並用fluo-4進行偵測，以此來偵測RD與RC13細胞本身鈣離子釋放之表現。根據我們研究發現，RD與RC13這兩株細胞本身並不帶有惡性高熱症之致病變異點，且都有可接受的轉染效率，再給予咖啡因刺激後也都有觀測到相較於HEK293細胞更貼近於正常人體生理情況相近的表現，因此我們認為此系統將能更有效且準確的模擬惡性高熱症的病理機轉，我們將對於過去我們團隊發表過的台灣幾個常見的點位（c.6488G>T, c.1565A>G）以及其他幾個已被證實為致病變異點（c.487C>T, c.7042_7044del）與良性的點位（c.2677G>A）進行測試，與現有系統進行比較，此將對於惡性高熱症的研究有重要的貢獻。 " | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:09:23Z (GMT). No. of bitstreams: 1 U0001-2510202115183200.pdf: 3471600 bytes, checksum: 277595aaff96ecc1bac202f7feb5295f (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 口試委員會審定書…………………………………………………….………………...i 致謝……………………………………………………………………………………...ii 中文摘要………………………………………………………………………………..iii Abstract…………………………………………………………………………………..v Contents…………………………………………………………………………...…...viii List of figures………………………………………………………….………………..ix List of tables..…………………………………….……………………………………...x 1. Introduction……………………………………..………………………………….1 2. Materials and methods…………………………………………………….………..6 3. Results……………………………………………………………….……………14 4. Discussion…………………………………………………………………………19 5. References…………………………………………………………………..…….26 | |
| dc.language.iso | en | |
| dc.subject | 鈣離子釋放 | zh_TW |
| dc.subject | 人類肌肉細胞株 | zh_TW |
| dc.subject | 惡性高熱症 | zh_TW |
| dc.subject | 功能性研究 | zh_TW |
| dc.subject | 人胚胎腎細胞293 | zh_TW |
| dc.subject | Malignant Hyperthermia (MH) | en |
| dc.subject | Functional Assay | en |
| dc.subject | Calcium Release | en |
| dc.subject | HEK293 | en |
| dc.subject | Human Muscle Cell Lines | en |
| dc.title | RYR1疑似惡性高熱症致病變異點之功能性研究 | zh_TW |
| dc.title | Functional Assays for Suspected Pathogenic Variants in RYR1 for Malignant Hyperthermia | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳佑宗(Hsin-Tsai Liu),葉惠敏(Chih-Yang Tseng),蔡丰喬 | |
| dc.subject.keyword | 惡性高熱症,人類肌肉細胞株,人胚胎腎細胞293,鈣離子釋放,功能性研究, | zh_TW |
| dc.subject.keyword | Malignant Hyperthermia (MH),Human Muscle Cell Lines,HEK293,Calcium Release,Functional Assay, | en |
| dc.relation.page | 64 | |
| dc.identifier.doi | 10.6342/NTU202104150 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-10-26 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 基因體暨蛋白體醫學研究所 | zh_TW |
| 顯示於系所單位： | 基因體暨蛋白體醫學研究所 | |
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| U0001-2510202115183200.pdf 授權僅限NTU校內IP使用（校園外請利用VPN校外連線服務） | 3.39 MB | Adobe PDF |
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