6月4日，《醫(yī)學(xué)遺傳學(xué)雜志》在線發(fā)表了上海生科院計(jì)算生物學(xué)研究所徐書(shū)華研究組的研究成果“Identification of well-differentiated gene expressions between Han Chinese and Japanese using genome-wide microarray data analysis”,。該項(xiàng)工作首次揭示了中國(guó)漢族與日本人之間在轉(zhuǎn)錄水平的差異,，并估計(jì)了遺傳變異對(duì)人群基因表達(dá)譜差異的貢獻(xiàn)率，有助于理解基因表達(dá)與遺傳變異之間的聯(lián)系,，并為闡明近緣人群之間表型差異的分子機(jī)制提供了線索,。
中國(guó)漢族和日本人有共同的遺傳起源，在外表形態(tài)上也存在很高的相似性,。然而,，雖然親緣關(guān)系如此緊密的兩個(gè)人群在人體性狀上的細(xì)微差異不易度量，但是人們普遍的印象是,，漢族和日本人在外表上的差異似乎還是能被人眼識(shí)別出來(lái),，盡管大多可能僅僅是文化、行為上的差異以及由此導(dǎo)致的視覺(jué)上可以察覺(jué)到的差異,。問(wèn)題在于,，從生物學(xué)的角度，漢族人與日本人之間究竟存在怎樣的性狀差異,？有多少是由于環(huán)境差異導(dǎo)致的,？有多少是由于遺傳因素影響而產(chǎn)生的？
要回答這些問(wèn)題并不容易,，一個(gè)主要的困難在于對(duì)視覺(jué)可見(jiàn)的最終表型如何度量和量化,，而這一點(diǎn)在近緣人群中尤其具有挑戰(zhàn)性。鑒于此，徐書(shū)華研究組決定從可以大規(guī)模量化的一種中間表型——基因表達(dá)譜入手,，對(duì)以上問(wèn)題進(jìn)行探索和探討,。這項(xiàng)研究正是這個(gè)課題的一部分工作。該研究對(duì)漢族人和日本人的全基因組表達(dá)譜芯片數(shù)據(jù)進(jìn)行了系統(tǒng)和細(xì)致的分析,?；虮磉_(dá)可能受到多種因素的影響,，即使在同一人群的不同個(gè)體之間也存在顯著波動(dòng),，盡管如此，該項(xiàng)研究結(jié)果顯示漢族人和日本人的基因表達(dá)譜存在整體上的差異,。與之對(duì)應(yīng)的是,，盡管漢族人與日本人在外表和遺傳上都存在較大的相似性，但是從基因組的角度,，漢族人和日本人可以得到很好的區(qū)分,。該研究通過(guò)比較分析，鑒定出在兩個(gè)人群之間存在高度表達(dá)差異的基因,，通過(guò)對(duì)復(fù)雜性狀關(guān)聯(lián)分析數(shù)據(jù)庫(kù)的搜索和基因功能注釋?zhuān)l(fā)現(xiàn)其中某些差異表達(dá)基因與人體血液和生化特性有關(guān),，還有一些基因與人體身高以及某些疾病相關(guān)。由于缺乏流行病學(xué)調(diào)查數(shù)據(jù)和最終表型數(shù)據(jù),，目前還不確定具體的聯(lián)系和機(jī)制,。該研究進(jìn)一步估計(jì)了遺傳變異對(duì)基因表達(dá)差異的貢獻(xiàn)率，結(jié)果顯示,，對(duì)于在漢族人和日本人之間存在顯著差異的基因表達(dá),，單個(gè)遺傳變異的貢獻(xiàn)在7%到43%之間。這些研究結(jié)果表明,，中國(guó)漢族和日本人的差異,，不僅僅是地理、語(yǔ)言和文化等方面的區(qū)別,，而是在生物學(xué)上存在系統(tǒng)性的差異,，這些差異是有可能通過(guò)自然科學(xué)研究手段精確量化和客觀描述的。
計(jì)算生物學(xué)所袁媛助理研究員和博士生楊玲等實(shí)施了具體分析工作,。該研究工作得到了國(guó)家自然科學(xué)基金,、中國(guó)科學(xué)院、上海市科委,、德國(guó)馬普學(xué)會(huì),、香港王寬誠(chéng)教育基金會(huì)等基金的資助。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
