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AJHG:研究揭示为什么人类比黑猩猩更易患癌症

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黑猩猩与人类有百分之九十六个基因组是相同的。而这4%的巨大差异引起了佐治亚理工学院的Soojin Yi的兴趣。例如,为什么人类具有较高的患癌风险,而黑猩猩很少患这种疾病? 在9月的<em>American Journal of Human Genetic</em>杂志上发表的一项研究中,Yi分析了每一个物种的脑组织样本。她发现某些DNA修饰(也称为甲基化)的差异性可能...
黑猩猩与人类有百分之九十六个基因组是相同的。而这4%的巨大差异引起了佐治亚理工学院的Soojin Yi的兴趣。例如,为什么人类具有较高的患癌风险,而黑猩猩很少患这种疾病?

在9月的<em>American Journal of Human Genetic</em>杂志上发表的一项研究中,Yi分析了每一个物种的脑组织样本。她发现某些DNA修饰(也称为甲基化)的差异性可能会导致表型的改变。结果还提示,DNA甲基化对于某些人类疾病相关的表型包括癌症和孤独症中起着重要的作用,Yi说:我们的研究表明,某些人类疾病可能是进化后生起源的,这样的研究结果从长远来看,可能有助于更好的开发治疗某些人类疾病的手段。

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DNA甲基化修饰基因的表达,但这一过程并不改变细胞的遗传信息。为了了解两个物种之间DNA甲基化有何不同,Yi和她的研究小组描绘了多个人类个体和黑猩猩前额叶皮层的全基因组甲基化图谱。他们发现数人类大脑中百个基因的甲基化水平表现出显著降低,相比较于黑猩猩大脑而言。这些基因中的大多数都与蛋白结合以及细胞代谢过程中有关。

Yi说:这些基因与自闭症、神经管缺陷、酒精和其他化学品的依赖相关。这表明物种之间的甲基化差异可能产生显著的功能性后果。这些基因甲基化的差异还可能与某些疾病包括癌症等有关。该项研究由佐治亚理工学院研究和教育项目(GT-FIRE)和美国国家科学基金会奖助金(MCB-0950896 BCS-0751481)创新基金资助。

编译自:<a title="" href="http://www.sciencedaily.com/releases/2012/08/120823142735.htm" target="_blank">Human-Chimp Genetic Differences: New Insights Into Why Humans Are More Susceptible to Cancer and Other Diseases</a>
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<img src="http://www.bioon.com/biology/UploadFiles/201208/2012082509410305.gif" alt="" width="115" height="150" border="0" />

<a title="" href="http://dx.doi.org/10.1016/j.ajhg.2012.07.024" target="_blank">doi:10.1016/j.ajhg.2012.07.024</a>
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<br/><strong>Divergent Whole-Genome Methylation Maps of Human and Chimpanzee Brains Reveal Epigenetic Basis of Human Regulatory Evolution.</strong><br/>


Jia Zeng, Genevieve Konopka, Brendan G. Hunt, Todd M. Preuss, Dan Geschwind, Soojin V. Yi.

DNA methylation is a pervasive epigenetic DNA modification that strongly affects chromatin regulation and gene expression. To date, it remains largely unknown how patterns of DNA methylation differ between closely related species and whether such differences contribute to species-specific phenotypes. To investigate these questions, we generated nucleotide-resolution whole-genome methylation maps of the prefrontal cortex of multiple humans and chimpanzees. Levels and patterns of DNA methylation vary across individuals within species according to the age and the sex of the individuals. We also found extensive species-level divergence in patterns of DNA methylation and that hundreds of genes exhibit significantly lower levels of promoter methylation in the human brain than in the chimpanzee brain. Furthermore, we investigated the functional consequences of methylation differences in humans and chimpanzees by integrating data on gene expression generated with next-generation sequencing methods, and we found a strong relationship between differential methylation and gene expression. Finally, we found that differentially methylated genes are strikingly enriched with loci associated with neurological disorders, psychological disorders, and cancers. Our results demonstrate that differential DNA methylation might be an important molecular mechanism driving gene-expression divergence between human and chimpanzee brains and might potentially contribute to the evolution of disease vulnerabilities. Thus, comparative studies of humans and chimpanzees stand to identify key epigenomic modifications underlying the evolution of human-specific traits.

<br/>来源:生物谷

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