動(dòng)物模型被廣泛的應(yīng)用在心血管疾病的研究中,，然而，利用這些動(dòng)物模型進(jìn)行實(shí)驗(yàn),，通常會(huì)發(fā)生實(shí)驗(yàn)結(jié)果達(dá)不到預(yù)期目標(biāo)或者大相徑庭,。
在構(gòu)建與發(fā)展人類疾病動(dòng)物模型過程中，最根本的問題是要清楚疾病基因在模式動(dòng)物中的功能保守性,。
為了深入探討人類心血管疾病動(dòng)物模型與人之間的差異,，在中國科學(xué)院昆明動(dòng)物研究所生物信息與系統(tǒng)生物學(xué)實(shí)驗(yàn)室黃京飛研究員的指導(dǎo)下，博士生趙玉琪與盛自章等對(duì)人類以及四種心血管疾病動(dòng)物模型（（小鼠,，大鼠,，獼猴，狗）的轉(zhuǎn)錄組進(jìn)行了全面細(xì)致的比較,。研究發(fā)現(xiàn),，盡管大部分基因受到強(qiáng)烈的負(fù)選擇,，但是有一些通路在動(dòng)物模型與人間發(fā)生了分化。并且,，不同的動(dòng)物模型與人之間發(fā)生分化的通路不盡相同,。共表達(dá)網(wǎng)絡(luò)結(jié)果還顯示，基因的表達(dá)演化并不是單獨(dú)發(fā)生的,，而是通過形成模塊共同演化的,。這項(xiàng)研究為更好的發(fā)展心血管疾病模型以及研究基因表達(dá)的演化提供了有力的數(shù)據(jù)及方法學(xué)支持。
該研究目前已在線發(fā)表于Molecular BioSystems,。該工作得到國家自然基金和云南省自然基金等的大力支持,。（生物谷 Bioon）
doi:10.1039/C1MB05415E
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A systematic analysis of heart transcriptome highlights divergent cardiovascular disease pathways between animal models and humans.
Yuqi Zhao , Zizhang Sheng and Jingfei Huang
Animal models have been extensively used in the study of cardiovascular disease (CVD) and have provided important insights into disease pathogenesis and drug development. However, the level of conservation of gene expression patterns of the orthologous genes between human and animal models was unclear. To address this issue, we compared the expression of orthologous genes in human and four models (rhesus, rat, mouse and dog), based on 42 normal heart samples with high quality gene expression data. The results show that the global expression profiles between animal model and human orthologous genes are highly preserved. The phylogenetic tree inferred from the gene expression profiles has similar topology to that of the species tree. However, differentially expressed genes (DEGs) between human and each model were identified and these four gene datasets are enriched with different molecular functions, including hormone-receptor binding and geranyl transferase activity. The 65 overlapped DEGs between four sets are involved in thyroid cancer, proteasome systems, aminoacyl-tRNA biosynthesis and GST (Glycine, Serine and Threonine) metabolism, of which functions are divergent between models and humans. In addition, 46.2% (30/65) of the communal genes have been experimentally proven to be associated with cardiovascular disease. Next, we constructed a co-expression network based on intra- and inter-species variation, to elucidate the altered network organization. It indicates that these DEGs evolved as modules rather than independently. The integrated heart transcriptome data should provide a valuable resource for the in-depth understanding of cardiology and the development of cardiovascular disease models.
