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核苷酸序列的模擬

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. 傳統的定義是以 X-ray 跟 NMR 來決定蛋白質結構等的問題。 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。 我感興趣的研究領域：核苷酸序列中各類特殊序列的成因。. The Nobel Prize in Physiology or Medicine 1962. Francis H. C. Crick. James D. Watson. Maurice H.F. Wilkins. DNA 結構. Coding region. Codon Table.

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核苷酸序列的模擬

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  1. 核苷酸序列的模擬 楊義清 於國家理論科學中心﹙南區﹚

  2. 生物物理 • 傳統的定義是以X-ray跟NMR來決定蛋白質結構等的問題。 • 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。 • 我感興趣的研究領域：核苷酸序列中各類特殊序列的成因。

  3. The Nobel Prize in Physiology or Medicine 1962 Francis H. C. Crick James D. Watson Maurice H.F. Wilkins

  4. DNA結構

  5. Coding region

  6. Codon Table

  7. microsatellite DNA • 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，中間沒有被其他鹼基打斷，所有的序列樣式均介於2~6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。

  8. Why interest in SSRs? • Important role in genetic disease, genome organization, and evolutionary processes • the most widely used markers for genetic mapping, evolution studies and forensic fingerprinting. • the length polymorphism of microsatelliters is frequently used in medical purpose.

  9. Medical Purposes • genetic mechanism of molecular event for evolution and progression of tumor. • such as endometrial carcinoma (Gurin et.al., 1999), hereditary nonpolyosis colorectal carcinoma (Eshleman & Markowitz, 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).

  10. 有關SSRs成因機制的研究 • The results of many researchers favor the model of polymerase template slippage (Henderson et.al.,1992; Morral et.al., 1991; Freudenreich et.al., 1997; Parker & Marinus, 1992) • Ohta 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.

  11. A continuous-time Markov chain model that incorporates slippage events and point mutations, a stationary was resulted (Kruglyak et.al., 1998; 1999) • Dokholyan et.al. (1997; 1998) analyed a simplified model of unequal chromosomal crossing over for expressing the power-law distribution Nonlinear model

  12. Han跟Li的研究﹙cond-mat/2025259﹚

  13. small world D.J. Watts and S.H. Strogatz, Nature 393, 440-442 (1998)

  14. 分析上所得到的結果 • SSR的長度分佈不是指數，也非對數 • SSR分布具有高度相關性(非隨機分布) • 這種影響已經不是slippage與point mutation能夠形成的 • 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 this mechanism?

  15. Microsatellite DNA Evolution

  16. About Future • 學習到什麼的物理新知？ • 如何藉由物理工具來協助生物學家瞭解各種分子生物學上長久存在的問題？

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