核苷酸序列的模拟ppt课件

1、核苷酸序列的模擬楊義清於國家理論科學中心南區生物物理n傳統的定義是以X-ray跟NMR來決定蛋白質結構等的問題。n用物理的方法來解決生物系統中的問題， 特別是以理論物理的方法。n我感興趣的研讨領域：核苷酸序列中各類特殊序列的成因。The Nobel Prize in Physiology or Medicine 1962Maurice H.F. WilkinsFrancis H. C. CrickJames D. Watson DNA結構Coding regionCodon Tablemicrosatellite DNAn指單一核苷酸序列樣式所組成的序列，從頭到尾都是由連續的序列樣式所組成，中

2、間沒有被其他鹼基打斷，一切的序列樣式均介於26個鹼基之間。尚有SSRs simple sequences repeats 和STRs short tandem repeats等這些代表連續重複序列的名稱。Why interest in SSRs?nImportant role in genetic disease, genome organization, and evolutionary processesnthe most widely used markers for genetic mapping, evolution studies and forensic fingerprinti

3、ng.nthe length polymorphism of microsatelliters is frequently used in medical purpose. Medical Purposesngenetic mechanism of molecular event for evolution and progression of tumor.nsuch as endometrial carcinoma Gurin et.al., 1999, hereditary nonpolyosis colorectal carcinoma Eshleman & Markowitz,

4、 1996, thyroid tumor Lazzereschi et.al., 1994, gastric cancer Rhyu et.al., 1994, pancreatic cancer Han et.al., 1993, and bladder tumor Orlow et.al., 1994.有關SSRs成因機制的研讨nThe results of many researchers favor the model of polymerase template slippage Henderson et.al.,1992; Morral et.al., 1991; Freudenr

5、eich et.al., 1997; Parker & Marinus, 1992nOhta and Kimura 1973 introduced the stepwise mutation model with the polymerase template slippage, and the microsatellite length follows a simple random walk with a reflecting barrier at one repeat unit.nA continuous-time Markov chain model that incorpor

6、ates slippage events and point mutations, a stationary was resulted Kruglyak et.al., 1998; 1999nDokholyan et.al. 1997; 1998 analyed a simplified model of unequal chromosomal crossing over for expressing the power-law distributionNonlinear modelHan跟Li的研讨cond-mat/2025259small worldD.J. Watts and S.H. Strogatz, Nature 393, 440-442 1998分析上所得到的結果nSSR的長度分佈不是指數，也非對數nSSR分布具有高度相關性非隨機分布n這種影響已經不是slippage與point mutation能夠构成的n進一步的想法是提出一個機制來模擬，但是要具有生物上的證據What is