以重複序列尋找可能之白色念珠菌致病基因

Abstract

白色念珠菌是一種伺機型的真菌，它會造成人類口腔以及陰道黏膜的感染，以及系統性的感染。近年來由於人類三核苷酸重複之疾病的發現，使得編碼重複這個議題又再度被提及。然而這些編碼重複的現象在酵母菌中也是存在的，但是對於它的結構以及功能大多是未知或者知道的很少。有研究指出在細菌及啤酒酵母菌中，細胞壁蛋白的編碼重複與免疫原性的改變以及黏附能力與發病機制有著很大的關聯性。因此想要知道在白色念珠菌中，有重複編碼的蛋白是否也跟致病力有關。本實驗利用電腦運算方式試圖找出編碼重複的氨基酸片段以及頻率次數，以KMP演算法為基礎開發一套程式系統，透過這個程式對白色念珠菌之genomic sequence進行探勘可以得到編碼重複之基因片段以及重複出現的頻率次數，提供後續的生物功能性研究，最終目的是要探討編碼重複之基因片段與致病能力或致病因子的相關性。實驗結果發現在所得的有編碼重複之基因中，已有部分被證實與致病能力有相關。其中當重複大小小於等於4者以及當重複次數大於5及重複大小大於4，重複次數小於5者最為明顯。

Candida albicans is an opportunistic fungal pathogen that causes oral and vaginal mucosal infections as well as systemic diseases. In recent years, the discovery of the trinucleotide repeat diseases in human has brought interests to tandem repeats. Tandem repeats regions are common in yeast FLO adhesins, but their structures are unknown, and their activities are poorly understood. In bacteria and yeasts FLO, coding repeats in cell wall proteins are associated with alterations in immunogenicity, adhesion, and pathogenesis. Deletion of one such gene may result in a phenotype characterized by rapid conidial germination and reduced adherence to extracellular matrix. Both phenotypes are associated with virulence. Hence, I am interested to know, whether the association between tandem repeats and virulence is also present in Candida albicans. I have acquired the sequences and frequency of ORF containing tandem repeats by computation strategies. I created a program based on Knuth Morris Pratt (KMP) algorithm. Secondly, I acquired ORFs containing repeat sequences and the frequency of the repeats utilizing this program. Then I surveyed the literature to check the known functions of those genes. I found that some of them have activities related to pathogenicity, especially for the with window size larger then 4 and repeat frequency between 2~4, as well as the window size small or equal to 4 and repeat frequency larger then 4.