英國(guó)桑格研究所16日發(fā)布新聞公報(bào)說(shuō)，他們發(fā)明一種快速高效分析細(xì)菌基因組中成千上萬(wàn)個(gè)基因的新技術(shù)，可以在一次實(shí)驗(yàn)中識(shí)別出“有用”的基因，從而防治細(xì)菌導(dǎo)致的疾病,。這種名為TraDIS技術(shù)的實(shí)質(zhì)是在基因?qū)用嫔系?ldquo;剪切和粘貼”。基因是DNA鏈上具有特定功能的一個(gè)片段,，如果將這個(gè)片段中一些地方“剪切”掉，再“粘貼”上一段抑制其功能的物質(zhì),，那么這個(gè)基因就會(huì)失去作用,。
如研究人員對(duì)傷寒沙門氏菌的每個(gè)基因都進(jìn)行了“剪切和粘貼”處理,，得到約100萬(wàn)個(gè)發(fā)生了不同基因變化的細(xì)菌，隨后,，將它們一起培養(yǎng),。那些因?yàn)榛蜃兓δ苁軗p的細(xì)菌不會(huì)生長(zhǎng)，于是在一次實(shí)驗(yàn)中識(shí)別出了“有用”基因,。結(jié)果顯示,，維持傷寒沙門氏菌基本生存的“有用”基因只有356個(gè)，其他數(shù)千個(gè)基因則不是必不可少的,。
研究人員稱,，這一技術(shù)有助于醫(yī)療研究。比如傷寒沙門氏菌常存在于攜帶者的膽囊中,，并由此傳染他人,，但這一傳染途徑的前提是細(xì)菌對(duì)膽汁要有抵抗能力。研究人員利用TraDIS技術(shù)在膽汁中培養(yǎng)細(xì)菌,，最終確定了169個(gè)與抵抗膽汁能力有關(guān)的基因,。在此基礎(chǔ)上研發(fā)治療手段，可以幫助防治傷寒沙門氏菌造成的疾病,。
相關(guān)研究報(bào)告發(fā)表在美國(guó)新一期《基因組研究》雜志上,。（生物谷Bioon.com）
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生物谷推薦原始出處：
Genome Research October 13, 2009, doi:10.1101/gr.097097.109
Simultaneous assay of every Salmonella Typhi gene using one million transposon mutants
Gemma C. Langridge1,6, Minh-Duy Phan1,6, Daniel J. Turner1,6, Timothy T. Perkins1, Leopold Parts1, Jana Haase2, Ian Charles3, Duncan J. Maskell4, Sarah E. Peters4, Gordon Dougan1, John Wain5, Julian Parkhill1,7 and A. Keith Turner1
1The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom;
2Environmental Research Institute, University College, Cork, Ireland;
3Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom;
4Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom;
5Laboratory of Gastrointestinal Pathogens, Centre for Infections, Health Protection Agency, Colindale, London NW9 5HT, United Kingdom
Very high-throughput sequencing technologies need to be matched by high-throughput functional studies if we are to make full use of the current explosion in genome sequences. We have generated a very large bacterial mutant pool, consisting of an estimated 1.1 million transposon mutants and we have used genomic DNA from this mutant pool, and Illumina nucleotide sequencing to prime from the transposon and sequence into the adjacent target DNA. With this method, which we have called TraDIS (transposon directed insertion-site sequencing), we have been able to map 370,000 unique transposon insertion sites to the Salmonella enterica serovar Typhi chromosome. The unprecedented density and resolution of mapped insertion sites, an average of one every 13 base pairs, has allowed us to assay simultaneously every gene in the genome for essentiality and generate a genome-wide list of candidate essential genes. In addition, the semiquantitative nature of the assay allowed us to identify genes that are advantageous and those that are disadvantageous for growth under standard laboratory conditions. Comparison of the mutant pool following growth in the presence or absence of ox bile enabled every gene to be assayed for its contribution toward bile tolerance, a trait required of any enteric bacterium and for carriage of S. Typhi in the gall bladder. This screen validated our hypothesis that we can simultaneously assay every gene in the genome to identify niche-specific essential genes.
