人類與小鼠組織特異表現基因之鑑別及其比較分析

In Silico Identification and Comparative Analysis of Tissue-Specific Genes in Human and Mouse

包盛盈(Sheng-Ying Pao)

指導教授 ： 林文澧

共同指導教授 ： 黃明經(Ming-Jing Hwang)

國立臺灣大學/工學院/醫學工程學研究所/碩士(2004年)

https://doi.org/10.6342/NTU.2004.01939

摘要

在不同組織中基因表現程度之差異對於維持以及調控細胞功能扮演十分重要的角色，而這些組織特異表現基因可以藉由比較各組織基因表現量之顯著差異來加以判斷。人類與小家鼠具有演化上相近之親緣關係，同時小家鼠亦廣為應用於當代生醫研究與臨床實驗之模式系統，本研究係由比較基因體學以及功能基因體學的角度來分析人類與小家鼠各組織具有顯著表現之基因。本計畫之方法為發展生物資訊學的程序根據表現序列標誌（EST）及其相應的標誌群集（EST cluster of UniGene）鑑別出組織特異表現之基因。目前本研究已鑑別出157種人類組織及108種小家鼠組織當中具有顯著表現的基因。其中我們將人類胎盤顯著表現基因之文獻與我們的結果比較顯示其97.2%的高度顯著基因與我們的預測（p<10-6）吻合，另外在人類大腦顯著表現基因之文獻與我們的結果比較顯示其100%的高度顯著基因與我們的預測（p<10-6）吻合。我們鑑定出的小家鼠腦內紋狀核(striatum)的基因中有86%的結果是與目前微陣列(microarray)的已知結果相符。我們並將人類與小家鼠組織特異表現之同源基因比較分析，整體而言其組織特異基因（p<10-6）之平均相關係數為0.6。另外，同源基因的個別相關係數分析則顯示人類與小家鼠表現組織之異同。這些結果已建立在一名為HMDEG之資料庫中，並提供圖形介面供使用者透過網路查詢。分析這些組織中特異表現的基因將有助於功能基因體學以及系統生物學的研究，這些基因不論在臨床研究或診斷上亦是理想的標的基因。

關鍵字

功能基因體學 ； 組織特異表現基因 ； 比較基因體學 ； 表現序列標誌

並列摘要

At the transcriptome level, differential expression of genes is important to maintain and regulate cellular functions. Tissue specific patterns of mRNA expression can provide important information about gene function. Genes expressed with tissue specificity can be characterized by their significantly different amount of transcripts found in different tissues. In this study, we have organized the EST libraries into hierarchical tissue classes and identified preferentially expressed genes in 157 human tissues and 108 mouse tissues by analyzing the EST database along with their clusters as collected in UniGene (build #161 for human and build #128 for mouse). In validation, we compared our results with tissue-specific genes reported in literature and microarray data. Our results yielded a prediction that covered 97.2% of placenta-specific genes and 100% of brain-specific genes reported in recent studies for human, and 86% of mouse striatum-specific genes identified in our results coincided with current findings of microarray data. We have comparatively analyzed 7854 homologous gene pairs. The average correlation coefficient of homologous tissue specific genes with statistical significance (p value < 10-6) reaches 0.6. Detailed analysis of homologous gene pairs reveals similarity and disparity in their expression pattern in human and mouse. We have created a database, named HMDEG (Human and Mouse Differentially Expressed Genes), and a user-friendly website for easy query of tissue-specific genes. The tissue-specific genes identified in this study may serve as targets for seeking candidate markers for genomic research and for investigating gene expression profiles in the scope of comparative genomics.

並列關鍵字

tissue-specific gene ； expression profile ； EST ； functional genomics ； UniGene ； comparative genomics

參考文獻

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