染色體不分離
染色體不分離(Nondisjunction)是指生物細胞分裂時,同源染色體或姊妹染色體未能成功分離的現象,由美國遺傳學家卡爾文·布里基斯和托馬斯·亨特·摩爾根於1910年在黑腹果蠅細胞的性染色體上發現[1]。染色體不分離包括第一次減數分裂時同源染色體不分離、第二次減數分裂時姊妹染色體不分離、以及有絲分裂時姊妹染色體不分離等三種情形[2][3][4]。
染色體不分離會造成子細胞成為非整倍體,即多出一條染色體或(2n+1)或失去一條染色體(2n-1)[4],若發生在減數分裂則可能造成子代發生非整倍體疾病,三體症(細胞具有3條該該對染色體)包括唐氏症、愛德華氏症候群、克氏綜合徵等[3][5];已知的單體症(細胞僅有1條該對染色體)則僅有透納氏症一種[3][5]。
人類的非整倍體疾病較多是女性減數分裂時(特別是第一次減數分裂[6])發生染色體不分離所致,可能原因是卵母細胞減數分裂過程中,會在前期I停滯數年至數十年之久,可能為使姊妹染色體失去黏連蛋白而相互分離,進而使著絲點連接錯誤[6][7],相較之下精母細胞則會快速地完成整個減數分裂流程;另外精母細胞減數分裂時發生染色體互換的頻率高於卵母細胞,人類卵母細胞有超過10%有至少一對同源染色分體在聯會過程中沒有發生互換,而缺乏互換是造成染色體不分離的原因之一[8]。有些物質(非整倍體誘變劑)可以促使細胞分裂時發生染色體不分離的現象,菸草即為一種非整倍體誘變劑,因此吸菸會提升染色體不分離的機率[9][10];另有研究顯示酒精[11]、苯[12]、氰戊菊酯[13]、甲萘威[14]等物質可能也是非整倍體誘變劑。
為避免細胞分裂時染色體不分離,細胞週期中有紡錘體組裝檢查點(SAC)以確保細胞中染色體均與紡錘體連接妥當後才活化促後期複合體(APC),使細胞分裂進入後期[15]。
參考文獻
- ^ Thomas Hunt Morgan. Sex-Linked Inheritance in Drosophila. Ulan Press. 2012-08-31: 10–11 [2021-12-11]. (原始內容存檔於2021-04-12).
- ^ Simmons, D. Peter Snustad, Michael J. Principles of genetics 4th. New York, NY [u.a.]: Wiley. 2006. ISBN 9780471699392.
- ^ 3.0 3.1 3.2 Bacino, C.A.; Lee, B. Chapter 76: Cytogenetics. Kliegman, R.M.; Stanton, B.F.; St. Geme, J.W.; Schor, N.F.; Behrman, R.E. (編). Nelson Textbook of Pediatrics, 19th Edition 19th. Philadelphia: Saunders. 2011: 394–413. ISBN 9781437707557.
- ^ 4.0 4.1 Strachan, Tom; Read, Andrew. Human molecular genetics 4th. New York: Garland Science. 2011. ISBN 9780815341499.
- ^ 5.0 5.1 Gleason, H. William; Taeusch, Roberta A.; Ballard, Christine A. (編). Avery's diseases of the newborn 8th. Philadelphia, Pa.: W.B. Saunders. 2005. ISBN 978-0721693477.
- ^ 6.0 6.1 Jones, K. T.; Lane, S. I. R. Molecular causes of aneuploidy in mammalian eggs. Development. 2013-08-27, 140 (18): 3719–3730. PMID 23981655. doi:10.1242/dev.090589 .
- ^ Eichenlaub-Ritter, Ursula. Oocyte ageing and its cellular basis. The International Journal of Developmental Biology. 2012, 56 (10–11–12): 841–852. PMID 23417406. doi:10.1387/ijdb.120141ue .
- ^ Nagaoka, SI; Hassold, TJ; Hunt, PA. Human aneuploidy: mechanisms and new insights into an age-old problem.. Nature Reviews Genetics. 2012-06-18, 13 (7): 493–504. PMC 3551553 . PMID 22705668. doi:10.1038/nrg3245.
- ^ Shi Q, Ko E, Barclay L, Hoang T, Rademaker A, Martin R. Cigarette smoking and aneuploidy in human sperm. Mol. Reprod. Dev. 2001, 59 (4): 417–21. PMID 11468778. S2CID 35230655. doi:10.1002/mrd.1048.
- ^ Rubes J, Lowe X, Moore D, Perreault S, Slott V, Evenson D, Selevan SG, Wyrobek AJ. Smoking cigarettes is associated with increased sperm disomy in teenage men. Fertil. Steril. 1998, 70 (4): 715–23. PMID 9797104. doi:10.1016/S0015-0282(98)00261-1.
- ^ Benassi-Evans B, Fenech M. Chronic alcohol exposure induces genome damage measured using the cytokinesis-block micronucleus cytome assay and aneuploidy in human B lymphoblastoid cell lines. Mutagenesis. 2011, 26 (3): 421–9. PMID 21273273. doi:10.1093/mutage/geq110 .
- ^ McHale CM, Smith MT, Zhang L. Application of toxicogenomic profiling to evaluate effects of benzene and formaldehyde: from yeast to human. Ann. N. Y. Acad. Sci. 2014, 1310 (1): 74–83. Bibcode:2014NYASA1310...74M. PMC 3978411 . PMID 24571325. doi:10.1111/nyas.12382.
- ^ Xia Y, Bian Q, Xu L, Cheng S, Song L, Liu J, Wu W, Wang S, Wang X. Genotoxic effects on human spermatozoa among pesticide factory workers exposed to fenvalerate. Toxicology. 2004, 203 (1–3): 49–60. PMID 15363581. doi:10.1016/j.tox.2004.05.018.
- ^ Xia Y, Cheng S, Bian Q, Xu L, Collins MD, Chang HC, Song L, Liu J, Wang S, Wang X. Genotoxic effects on spermatozoa of carbaryl-exposed workers. Toxicol. Sci. 2005, 85 (1): 615–23. PMID 15615886. doi:10.1093/toxsci/kfi066 .
- ^ Sun, S.-C.; Kim, N.-H. Spindle assembly checkpoint and its regulators in meiosis. Human Reproduction Update. 2011-11-14, 18 (1): 60–72. PMID 22086113. doi:10.1093/humupd/dmr044 .