近日，國際著名雜志PLoS ONE在線刊登了了上海生科院計(jì)算生物學(xué)所金力教授等的最新研究成果“A Map of Copy Number Variations in Chinese Populations,。”,。該項(xiàng)工作構(gòu)建了首張包括中國漢族和少數(shù)民族在內(nèi)的拷貝數(shù)變異圖譜,，為研究中國人群的基因組多樣性、群體分化和環(huán)境適應(yīng)以及復(fù)雜性狀基因定位提供了新的視角和數(shù)據(jù)信息參考,。
拷貝數(shù)變異（Copy Number Variation,，CNV）是近幾年人類基因組和遺傳學(xué)領(lǐng)域研究的熱點(diǎn)。到目前為止,，對中國人群的拷貝數(shù)變異研究,，正如幾乎所有的全基因組關(guān)聯(lián)研究（GWAS）都在漢族人中進(jìn)行一樣，無論是大型國際合作計(jì)劃還是國內(nèi)獨(dú)立開展的工作多集中在漢族人群,。然而,，一方面，中國人群的遺傳多樣性絕大部分存在于少數(shù)民族人群中,，另一方面,，對于基因功能和表型拷貝數(shù)變異的相對其他變異如單核苷酸多態(tài)的效應(yīng)要大得多，但是其頻率也較低,，以至于在全基因組尋找與特定表型或疾病關(guān)聯(lián)的拷貝數(shù)變異往往需要參考數(shù)據(jù)庫,。該項(xiàng)工作利用Affymetrix芯片技術(shù)，通過近1百萬個(gè)拷貝數(shù)變異探針的信息,，在中國漢族,、藏族、侗族,、瑤族,、壯族、黎族和維吾爾族群體樣本中檢測了全基因組范圍的拷貝數(shù)變異,；并系統(tǒng)比較和分析了少數(shù)民族和漢族以及中國人群與世界其他大洲人群的基因組多樣性和群體差異,。研究發(fā)現(xiàn)少數(shù)民族人群與漢族人群不共享的拷貝數(shù)變異區(qū)域多達(dá)35%；與歐洲人群的研究結(jié)果相比,，標(biāo)簽拷貝數(shù)變異（tag CNV）在中國人群之間的可移植性要低很多,，提示全面研究中國人群拷貝數(shù)變異的必要性。進(jìn)一步的研究表明,，群體特異性的拷貝數(shù)變異可能與人群對其特定生存環(huán)境的長期適應(yīng)有關(guān),。
該工作由博士生樓海一在導(dǎo)師金力教授和徐書華研究員的指導(dǎo)下，與復(fù)旦大學(xué)及哈佛兒科醫(yī)院的研究人員合作完成,。該研究工作得到了國家自然科學(xué)基金委,、上海市科委,、中國科學(xué)院、德國馬普學(xué)會,、香港王寬誠教育基金會等多項(xiàng)基金的資助,。（生物谷Bioon.com）
doi:10.1371/journal.pone.0027341
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A Map of Copy Number Variations in Chinese Populations
Haiyi Lou1#, Shilin Li2#, Yajun Yang2, Longli Kang2, Xin Zhang2, Wenfei Jin1, Bailin Wu2,3, Li Jin1,2*, Shuhua Xu1*
It has been shown that the human genome contains extensive copy number variations (CNVs). Investigating the medical and evolutionary impacts of CNVs requires the knowledge of locations, sizes and frequency distribution of them within and between populations. However, CNV study of Chinese minorities, which harbor the majority of genetic diversity of Chinese populations, has been underrepresented considering the same efforts in other populations. Here we constructed, to our knowledge, a first CNV map in seven Chinese populations representing the major linguistic groups in China with 1,440 CNV regions identified using Affymetrix SNP 6.0 Array. Considerable differences in distributions of CNV regions between populations and substantial population structures were observed. We showed that ~35% of CNV regions identified in minority ethnic groups are not shared by Han Chinese population, indicating that the contribution of the minorities to genetic architecture of Chinese population could not be ignored. We further identified highly differentiated CNV regions between populations. For example, a common deletion in Dong and Zhuang (44.4% and 50%), which overlaps two keratin-associated protein genes contributing to the structure of hair fibers, was not observed in Han Chinese. Interestingly, the most differentiated CNV deletion between HapMap CEU and YRI containing CCL3L1 gene reported in previous studies was also the highest differentiated regions between Tibetan and other populations. Besides, by jointly analyzing CNVs and SNPs, we found a CNV region containing gene CTDSPL were in almost perfect linkage disequilibrium between flanking SNPs in Tibetan while not in other populations except HapMap CHD. Furthermore, we found the SNP taggability of CNVs in Chinese populations was much lower than that in European populations. Our results suggest the necessity of a full characterization of CNVs in Chinese populations, and the CNV map we constructed serves as a useful resource in further evolutionary and medical studies.
