染色體不分離

维基百科,自由的百科全书
1. 第一次減數分裂
2. 第二次減數分裂
3. 受精
4. 合子

左圖的藍色箭頭指第二次減數分裂中發生染色體不分離,右圖的綠色箭頭指第一次減數分裂中發生染色體不分離

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·布里基斯英语Calvin Bridges托马斯·亨特·摩尔根於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综合征[3][5];已知的單體症英语Monosomy(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连蛋白英语cohesin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(非整倍体诱变剂英语aneugen)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体诱变剂,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][12]氰戊菊酯[13]甲萘威[14]等物質可能也是非整倍体诱变剂。

為避免細胞分裂時染色體不分離,細胞週期中有纺锤体组装检查点英语Spindle checkpoint(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英语Anaphase-promoting complex(APC),使細胞分裂進入後期英语Anaphase[15]

參考文獻

  1. ^ Thomas Hunt Morgan. Sex-Linked Inheritance in Drosophila. Ulan Press. 2012-08-31: 10–11 [2021-12-11]. (原始内容存档于2021-04-12). 
  2. ^ Simmons, D. Peter Snustad, Michael J. Principles of genetics 4th. New York, NY [u.a.]: Wiley. 2006. ISBN 9780471699392. 
  3. ^ 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. (编). Nelson Textbook of Pediatrics, 19th Edition 19th. Philadelphia: Saunders. 2011: 394–413. ISBN 9781437707557. 
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  7. ^ 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可免费查阅. 
  8. ^ 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可免费查阅. PMID 22705668. doi:10.1038/nrg3245. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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可免费查阅. 
  12. ^ 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可免费查阅. PMID 24571325. doi:10.1111/nyas.12382. 
  13. ^ 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. 
  14. ^ 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可免费查阅. 
  15. ^ 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可免费查阅.