包括來自美國(guó)國(guó)立衛(wèi)生研究院在內(nèi)的一組研究人員發(fā)現(xiàn)了一種新的探索人類基因組的方法。新方法涉及觀察基因組DNA三維形狀,，不僅僅是閱讀DNA堿基對(duì)的順序,。
發(fā)表在科學(xué)雜志網(wǎng)絡(luò)版在的一篇論文顯示上述結(jié)果。由國(guó)立人類基因組研究所（NHGRI）所埃利奧特格莉絲博士和波士頓大學(xué)托馬斯圖利烏斯博士領(lǐng)導(dǎo)的研究小組發(fā)現(xiàn)了一個(gè)新的方法檢測(cè)基因組區(qū)域功能,。相結(jié)化學(xué)和計(jì)算機(jī)分析,，研究人員能夠觀查 DNA結(jié)構(gòu)、區(qū)域與生物學(xué)功能的相關(guān)性,。
該方法包括確定構(gòu)成人類基因組DNA所有的溝槽,、突起和翻轉(zhuǎn)，然后與出現(xiàn)在其他動(dòng)物物種的基因組這些結(jié)構(gòu)進(jìn)行比較,。在許多物種中被保存下來的的相同結(jié)構(gòu)可能在生命體中發(fā)揮重要的作用,，而那些通過進(jìn)化改變了的基因組可能發(fā)揮核心作用少或根本沒有作用。
“這是一個(gè)令人興奮的新方法，將加速我們確定基因組功能,，這是我們進(jìn)行基因組研究所面臨的主要挑戰(zhàn),，”NHGRI主任埃里克博士表示，“DNA測(cè)序列方法的持續(xù)創(chuàng)新,，加速我們利用基因組信息改善人類健康的速度,。”（生物谷Bioon.com）
生物谷推薦原始出處：
Science March 12, 2009 DOI: 10.1126/science.1169050
Local DNA Topography Correlates with Functional Noncoding Regions of the Human Genome
Stephen C. J. Parker 1, Loren Hansen 2, Hatice Ozel Abaan 3, Thomas D. Tullius 4*, Elliott H. Margulies 3*
1 Bioinformatics Program, Boston University, Boston, MA 02215, USA.
2 Bioinformatics Program, Boston University, Boston, MA 02215, USA.; National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD, USA.
3 Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
4 Bioinformatics Program, Boston University, Boston, MA 02215, USA.; Department of Chemistry, Boston University, Boston, MA 02215, USA.
The three-dimensional molecular structure of DNA, specifically the shape of the backbone and grooves of genomic DNA, can be dramatically affected by nucleotide changes, which can cause differences in protein binding affinity and phenotype. We developed an algorithm to measure constraint on the basis of similarity of DNA topography among multiple species using hydroxyl radical cleavage patterns to interrogate the solvent accessible surface area of DNA. This algorithm found that 12% of bases in the human genome are evolutionarily constrained—double the number detected by nucleotide sequence-based algorithms. Topography-informed constrained regions correlated with functional noncoding elements, including enhancers, better than regions identified solely on the basis of nucleotide sequence. These results support that the molecular shape of DNA is under selection and can identify evolutionary history.
