生物谷報(bào)道：一個(gè)國(guó)際研究小組于最近宣布已經(jīng)完成了與人類(lèi)瘧疾寄生蟲(chóng)惡性瘧原蟲(chóng)遺傳變異性有關(guān)的基因圖譜的繪制,。12月10日提前出版的網(wǎng)上版《自然遺傳學(xué)》雜志已經(jīng)發(fā)表了這一研究成果：該研究揭示了病原體基因組的驚人變異,，包括一個(gè)由全球各地收集病原體樣本建立含大約47，000特定的遺傳變異的初步目錄,。這些差異的發(fā)現(xiàn)為剖析主要病原體基因的功能，跟蹤全球范圍內(nèi)瘧疾的發(fā)生奠定了基礎(chǔ),。由哈佛公共衛(wèi)生學(xué)院和美國(guó)麻省哈佛總醫(yī)院科學(xué)家領(lǐng)導(dǎo),，塞內(nèi)加爾的研究人員共同參與的這項(xiàng)研究已經(jīng)發(fā)現(xiàn)了對(duì)目前治療瘧疾藥物產(chǎn)生抗性的基因。
哈佛大學(xué)公共衛(wèi)生學(xué)院免疫和傳染系主任,、麻省哈佛總醫(yī)院傳染科共同主任,、此項(xiàng)研究主要負(fù)責(zé)人Dyann Wirth教授說(shuō)：“瘧疾之所以仍然能對(duì)全球公共衛(wèi)生產(chǎn)生威脅，主要是因?yàn)榀懠布纳x(chóng)致病基因的遺傳變異性造成的,。這項(xiàng)研究使我們第一次從瘧原蟲(chóng)基因組上看到其遺傳變異,，為使用基因工具研究瘧疾邁出了關(guān)鍵的一步”。惡性瘧原蟲(chóng)是使人類(lèi)患瘧疾的四種瘧原蟲(chóng)中毒性最強(qiáng)的一種,，平均每30秒鐘就有一個(gè)人死于這種瘧原蟲(chóng)導(dǎo)致的瘧疾，其中大多數(shù)是非洲的兒童,。盡管已經(jīng)研究了幾十年,，人們對(duì)惡性瘧原蟲(chóng)是如何通過(guò)遺傳轉(zhuǎn)變逃脫人體自身免疫系統(tǒng)的,，以及如何抵抗瘧疾藥物的等問(wèn)題依然知之甚少。
為了得到全球范圍內(nèi)廣泛的惡性瘧原蟲(chóng)基因變化圖譜,，科學(xué)家分析了采集自不同地理區(qū)域的50份樣本,，包括兩個(gè)深入研究的樣本的基因組全長(zhǎng)序列和另外16份隔離種群的DNA序列分析。這部分工作由波士頓地區(qū)的研究者和由the Cheikh Anta Diop 大學(xué)教授Souleymane Mboup領(lǐng)導(dǎo)的塞內(nèi)加爾的研究人員合作完成,，是同時(shí)發(fā)表在《自然遺傳學(xué)》上三項(xiàng)大規(guī)模的寄生蟲(chóng)DNA序列研究之一,。通過(guò)這些樣本基因序列的比對(duì)，并且同時(shí)與2002年發(fā)表的P. falciparum基因組做比對(duì),，科學(xué)家發(fā)現(xiàn)差異及其顯著：有大約47,，000個(gè)單核苷酸變異即單核苷酸多態(tài)性（SNPs）。這些進(jìn)化上差異的信息可以幫助發(fā)現(xiàn)與瘧疾抗藥性有關(guān)基因,，抗藥性基因的存在是控制瘧疾的主要障礙物,。用多種抗瘧疾藥物作用于各種瘧原蟲(chóng)，比較瘧原蟲(chóng)遺傳圖譜的差異,，科學(xué)家發(fā)現(xiàn)在息瘧定作用下瘧原蟲(chóng)一段序列高度螺旋,，同時(shí)確認(rèn)了與氯奎抗藥性有關(guān)的序列。麻省哈佛總醫(yī)院博士后,，文章第一作者Pardis Sabeti說(shuō)：“研究人類(lèi)進(jìn)化時(shí)使用的遺傳原理,，可以為瘧疾研究提供重要線(xiàn)索。從遺傳圖譜中已經(jīng)可以洞察與不同藥物處理相關(guān)的遺傳轉(zhuǎn)變,，這將為我們發(fā)現(xiàn)抗藥性基因提供可能,。”
遺傳圖譜同時(shí)可以解釋不同種群的遺傳景觀(guān)。通過(guò)遺傳圖譜比較不同大洲上的瘧原蟲(chóng),，科學(xué)家發(fā)現(xiàn)從非洲采集的樣本與從亞洲和美洲采集的樣本在DNA水平上有巨大差異,。這些知識(shí)可以指導(dǎo)示蹤瘧原蟲(chóng)傳播的遺傳標(biāo)志的選擇，特別是針對(duì)那些有毒或者耐藥的瘧原蟲(chóng),。同時(shí),，也將為把不同地域瘧原蟲(chóng)基因與其特征聯(lián)系起來(lái)，支持世界各地瘧疾的研究奠定基礎(chǔ),。
Figure 1. Geographic distribution of parasites and SNPs.
(a) Sequence data derived from 18 parasites were used for SNP identification, including HB3 (red) and Dd2 (green), for which we obtained the full genome sequence; 12 additional parasites (blue) for which we obtained low-coverage sequence and four additional parasites (gray) that were used with the 12 low-coverage parasites for PCR product sequencing of 20 core regions across the genome (Supplementary Table 2). (b) SNPs identified from the parasites shown in a provide four data sources, including full-genome sequencing of HB3 (red) and Dd2 (green), low-coverage sequencing of 12 additional parasites (blue) and sequencing of 18 kb across 20 core regions (PCR) in 16 parasites (gray). The total number of SNPs identified for each of the four sources (HB3, Dd2, low coverage and PCR) is indicated by source, totaling 46,937 overall. The inner pie chart (light shading) indicates the number of SNPs by source that were found in more than one source ('shared'), identifying a total of 12,188 individual SNP positions that were identified in at least two sources. The outer pie chart (dark shading) indicates the number of SNPs identified only in a single source ('private').
原文出處：
Nature Genetics December 2006 - Vol 38 No 12
A genome-wide map of diversity in Plasmodium falciparum
Sarah K Volkman, Pardis C Sabeti, David DeCaprio, Daniel E Neafsey, Stephen F Schaffner, Danny A Milner Jr, Johanna P Daily, Ousmane Sarr, Daouda Ndiaye, Omar Ndir, Soulyemane Mboup, Manoj T Duraisingh, Amanda Lukens, Alan Derr, Nicole Stange-Thomann, Skye Waggoner, Robert Onofrio, Liuda Ziaugra, Evan Mauceli, Sante Gnerre, David B Jaffe, Joanne Zainoun, Roger C Wiegand, Bruce W Birren, Daniel L Hartl, James E Galagan, Eric S Lander & Dyann F Wirth
Published online: 10 December 2006 | doi:10.1038/ng1930
Abstract | Full text | PDF (362K) | Supplementary Information
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作者簡(jiǎn)介：
Pardis Sabeti
Presenters
Broad Institute
http://www.broad.mit.edu/index.html
Pardis Sabeti is an M.D. Ph.D and graduate from MIT, Oxford and Harvard where she studied human evolution. She is also the lead singer and guitarist for the rock band Thousand Days. She is a Rhodes Scholar and was only the third woman ever to graduate Harvard Medical School with highest honors, summa cum laude. Her groundbreaking research on human evolution with advisor Eric Lander has been in the world's top journals, including Nature and Science. With already over 20 publications to her name, she is an expert in the study of recent human evolution and infectious disease. She is a co-investigator on project studying the malaria genome, and her team has just received a $2 million Gates Foundation Grant for their work. She has also received a Soros Fellowship, a L'Oreal For Women in Science Fellowship, a Burroughs Wellcome Career Award in Biomedical Sciences, a Damon Runyan Cancer Research Fellowship, and was named a Science Spectrum Magazine Trailblazer. She has also served on the MIT Board of Trustees and is a member of the Senior Common Room of Harvard University Winthrop House.
