6月4日，《医学遗传学杂志》在线发表了上海生科院计算生物学研究所徐书华研究组的研究成果“Identification of well-differentiated gene expressions between Han Chinese and Japanese using genome-wide microarray data analysis”。该项工作首次揭示了中国汉族与日本人之间在转录水平的差异，并估计了遗传变异对人群基因表达谱差异的贡献率，有助于理解基因表达与遗传变异之间的联系，并为阐明近缘人群之间表型差异的分子机制提供了线索。
中国汉族和日本人有共同的遗传起源，在外表形态上也存在很高的相似性。然而，虽然亲缘关系如此紧密的两个人群在人体性状上的细微差异不易度量，但是人们普遍的印象是，汉族和日本人在外表上的差异似乎还是能被人眼识别出来，尽管大多可能仅仅是文化、行为上的差异以及由此导致的视觉上可以察觉到的差异。问题在于，从生物学的角度，汉族人与日本人之间究竟存在怎样的性状差异？有多少是由于环境差异导致的？有多少是由于遗传因素影响而产生的？
要回答这些问题并不容易，一个主要的困难在于对视觉可见的最终表型如何度量和量化，而这一点在近缘人群中尤其具有挑战性。鉴于此，徐书华研究组决定从可以大规模量化的一种中间表型——基因表达谱入手，对以上问题进行探索和探讨。这项研究正是这个课题的一部分工作。该研究对汉族人和日本人的全基因组表达谱芯片数据进行了系统和细致的分析。基因表达可能受到多种因素的影响，即使在同一人群的不同个体之间也存在显着波动，尽管如此，该项研究结果显示汉族人和日本人的基因表达谱存在整体上的差异。与之对应的是，尽管汉族人与日本人在外表和遗传上都存在较大的相似性，但是从基因组的角度，汉族人和日本人可以得到很好的区分。该研究通过比较分析，鉴定出在两个人群之间存在高度表达差异的基因，通过对复杂性状关联分析数据库的搜索和基因功能注释，发现其中某些差异表达基因与人体血液和生化特性有关，还有一些基因与人体身高以及某些疾病相关。由于缺乏流行病学调查数据和最终表型数据，目前还不确定具体的联系和机制。该研究进一步估计了遗传变异对基因表达差异的贡献率，结果显示，对于在汉族人和日本人之间存在显着差异的基因表达，单个遗传变异的贡献在7%到43%之间。这些研究结果表明，中国汉族和日本人的差异，不仅仅是地理、语言和文化等方面的区别，而是在生物学上存在系统性的差异，这些差异是有可能通过自然科学研究手段精确量化和客观描述的。
计算生物学所袁媛助理研究员和博士生杨玲等实施了具体分析工作。该研究工作得到了国家自然科学基金、中国科学院、上海市科委、德国马普学会、香港王宽诚教育基金会等基金的资助。（生物谷Bioon.com）
生物谷推荐英文摘要：
J Med Genet doi:10.1136/jmedgenet-2012-101501
Identification of well-differentiated gene expressions between Han Chinese and Japanese using genome-wide microarray data analysis
Yuan Yuan, Ling Yang, Meng Shi, Dongsheng Lu, Haiyi Lou, Yi-Ping Phoebe Chen, Li Jin, Shuhua Xu
Background Investigating variations in gene expression, which can be quantitatively measured on a genome-wide scale, is essential to understand and interpret phenotypic differences among human populations. Several previous studies have examined and compared variations in gene expression between continental populations. However, differences in gene expression variation between closely related populations have not been studied yet.
Method We performed a genome-wide analysis and systematically compared expression profiles of Han Chinese with those of the Japanese population.
Results We identified 768 genes (4.4% of 17?354 expressed genes) which were expressed differentially between the two populations, with 165 showing highly differential expression and enriched in genes involved in the spliceosome pathway, mRNA processing, mRNA metabolic process, RNA processing, RNA splicing and mitochondrial transport. We further identified cis- and trans-variants that regulated these differential gene expressions, and found that cis-variants shared in the two populations were centred within a range of 200?kb around transcription start site. Our analysis indicated that genetic differences in the cis-associated genes between the two populations could explain 7–43% of the identified expression divergence.
Conclusions In summary, despite considerable heterogeneity, gene expression profiles between Han Chinese and Japanese did show an overall difference, with well-differentiated expressions regulated by genetic variants which have been reported associated with hematological and biochemical traits in Japanese populations. Our results supported that gene expression is regulated by genetic variants and there is a genetic basis for the phenotypic differences between Han Chinese and Japanese populations.
