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Title: 透過比較基因體學尋找具功能性的簡單重複序列
Discovering Functional Simple Sequence Repeat through Comparative Genomics
Authors: Chien-Ming Chen
Contributors: NTOU:Department of Computer Science and Engineering
Keywords: 比較基因體學;簡單重複序列;同源基因;基因本體論;遺傳疾病
Comparative Genomics;Simple Sequence Repeat;Homologous Gene;Gene Ontology;Genetic Disease
Date: 2009
Issue Date: 2011-06-22T08:43:08Z
Abstract: 簡單重複序列是在基因組序列中由長度由一到六個鹼基對片段串連而成的序列。這些重複序列除了作為基因標記使用外,近來的研究發現部分簡單重複序列在基因調控中扮演重要的角色,簡單重複序列的異常也可能會導致不同的遺傳疾病。因此,若是能辨識出具有功能性的簡單重複序列,將可以進一步了解基因調控機制、提供遺傳疾病篩檢的依據、或是對經濟物種的培育帶來極大的好處。但是由於基因組序列中的簡單重複序列數量過於龐大,僅藉由序列本身將很難辨識具有基因調控功能的簡單重複序列,因此本論文提出一種基於自相關比對技術來尋找簡單重複序列之高效率演算法,並針對多個模式物種建立全基因組簡單重複序列資料庫。提供跨物種基因組保留區域與同源基因等比較基因體學資訊,以篩選潛在功能性簡單重複序列之用,本系統並內建退化性引子設計功能供使用者進一步設計生物實驗之實際應用。除此之外,針對不同基因本體論之關鍵字所形成之基因群組,進行跨物種的過表現分析比較,可以歸納出不同基因功能與簡單重複序列樣式的關連性,藉此篩選出與特定功能基因群相關的簡單重複序列。最後,本論文所提出之核心技術可以整合線上人類孟德爾遺傳疾病資料庫,針對遺傳疾病尋找潛在的簡單重複序列基因調控子。
Simple Sequence Repeats (SSRs) are sequences of repeated nucleotides in genomes consisting of a continuous repeated basic pattern from moninucleotide to hexanucleotide. SSRs are usually employed as genetic markers, but recent studies have shown that some SSRs played important roles in gene regulation and SSR disorder may cause different genetic diseases. Therefore, identifying functional SSRs becomes useful in various applications such as understanding genes regulation, screening genetic diseases, and breeding for economic species. However, due to abundant number of SSRs within each genome, it’s very difficult to identify functional SSRs from individual genome sequences. Hence, in this study, an efficient algorithm based on auto-correlation for discovering functional SSRs in-silico was proposed, and a genomic range SSR database for multiple model species was built as well. This database provides comparative genomics information including cross-species gene conserved regions and homologous genes for filtering putative functional SSRs. A degenerate primer design tool is also available to facilitate biologists for designing biological experiments. Furthermore, based on the cross species analysis of over representation of SSRs within different gene subsets annotated by Gene Ontology terms, we have observed the connection between the gene functions and several specific SSR patterns. Finally, the Online Mendelian Inheritance In Man (OMIM) database was also integrated with the core searching techniques for detecting unknown SSR regulators of genetic diseases.
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