核苷酸序列的模擬ppt課件

1、核苷酸序列的模擬楊義清於國(guó)家理論科學(xué)中心南區(qū)生物物理n傳統(tǒng)的定義是以X-ray跟NMR來決定蛋白質(zhì)結(jié)構(gòu)等的問題。n用物理的方法來解決生物系統(tǒng)中的問題， 特別是以理論物理的方法。n我感興趣的研討領(lǐng)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(jié)構(gòu)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(xù)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(gè)鹼基之間。尚有SSRs simple sequences repeats 和STRs short tandem repeats等這些代表連續(xù)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., 2019), hereditary nonpolyosis colorectal carcinoma (Eshleman & Markowi

4、tz, 2019), 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(guān)SSRs成因機(jī)制的研討nThe results of many researchers favor the model of polymerase template slippage (Henderson et.al.,1992; Morral et.al., 1

5、991; Freudenreich et.al., 2019; Parker & Marinus, 1992)nOhta 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 mod

6、el that incorporates slippage events and point mutations, a stationary was resulted (Kruglyak et.al., 2019; 2019)nDokholyan et.al. (2019; 2019) analyed a simplified model of unequal chromosomal crossing over for expressing the power-law distributionNonlinear modelHan跟Li的研討cond-mat/2025259small worldD.J. Watts and S.H. Strogatz, Nature 393, 440-442 (2019)分析上所得到的結(jié)果nSSR的長(zhǎng)度分佈不是指數(shù)，也非對(duì)數(shù)nSSR分布具有高度相關(guān)性(非隨機(jī)分布)n這種影響已經(jīng)不是slippage與point mutation能夠構(gòu)成的n進(jìn)一步的想法是提出一個(gè)機(jī)制來模擬，但是要具有生物上的證據(jù)What is