2012年9月8日 訊 /生物谷BIOON/ --來自美國凱斯西儲大學(Case Western Reserve University)和克利夫蘭診所勒納研究所(Cleveland Clinic Lerner Research Institute )的研究人員發(fā)現(xiàn)導致最常見瘧疾類型的瘧原蟲---間日瘧原蟲(Plasmodium vivax)---擁有相同的基因變異，即便這種瘧原蟲是從不同大陸分離到的,。這項發(fā)現(xiàn)讓人們擔心,，抵抗現(xiàn)存藥物的突變能夠在全世界擴散，從而使得全球根除瘧疾的努力更加困難,。
包括克利夫蘭診所勒納研究所研究員David Serre和Peter Zimmerman,、Didier Menard(柬埔寨巴斯德研究所)和Arsene Ratsimbasoa(馬達加斯加國家瘧疾控制項目)在內(nèi)的研究人員是第一次對覆蓋范圍內(nèi)病人身上提取的間日瘧原蟲基因組進行測序，以便證實全基因組范圍的DNA序列變異,。這種有機體的基因組含有它的所有可遺傳性的信息,。相關研究結(jié)果在9月6日刊登在PLoS Neglected Tropical Diseases期刊上。
科學家首先吃驚地發(fā)現(xiàn)在來自馬達加斯加,、柬埔寨和南美洲的人們的樣品中,，很少有不同位點特異性的基因變異。
在這項研究中,，研究人員在首先除去白細胞之后,，對來自2名馬達加斯加病人和3名柬埔寨病人體內(nèi)的血液樣品中的間日瘧原蟲進行基因組測序。作為對比,，他們在遭受在南美洲發(fā)現(xiàn)的人間日瘧原蟲菌株感染的一只猴子體內(nèi),，獲取間日瘧原蟲，并對這種瘧原蟲進行基因組測序,。這些結(jié)果證實這6種樣品廣泛地擁有相同的等位基因,。
如今，研究人員鑒定出8萬個遺傳標記,，這些標記能夠被用來尋找它們與耐藥性瘧疾之間的關聯(lián)性,。
研究人員將利用這些數(shù)據(jù)進行遺傳進化研究來了解間日瘧原蟲是如何起源的，它是如何擴散的,，以及不同的菌株在地理上是如何分布的,。同時他們也將研究這種不斷進化的瘧原蟲的感染機制,。(生物谷Bioon.com)
doi: 10.1371/journal.pntd.0001811
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Whole Genome Sequencing of Field Isolates Provides Robust Characterization of Genetic Diversity in Plasmodium vivax
Ernest R. Chan1#, Didier Menard2#*, Peter H. David3, Arsène Ratsimbasoa4, Saorin Kim2, Pheaktra Chim2, Catherine Do2, Benoit Witkowski2, Odile Mercereau-Puijalon3*, Peter A. Zimmerman5¶*, David Serre
Background An estimated 2.85 billion people live at risk of Plasmodium vivax transmission. In endemic countries vivax malaria causes significant morbidity and its mortality is becoming more widely appreciated, drug-resistant strains are increasing in prevalence, and an increasing number of reports indicate that P. vivax is capable of breaking through the Duffy-negative barrier long considered to confer resistance to blood stage infection. Absence of robust in vitro propagation limits our understanding of fundamental aspects of the parasite's biology, including the determinants of its dormant hypnozoite phase, its virulence and drug susceptibility, and the molecular mechanisms underlying red blood cell invasion. Methodology/Principal Findings Here, we report results from whole genome sequencing of five P. vivax isolates obtained from Malagasy and Cambodian patients, and of the monkey-adapted Belem strain. We obtained an average 70–400 X coverage of each genome, resulting in more than 93% of the Sal I reference sequence covered by 20 reads or more. Our study identifies more than 80,000 SNPs distributed throughout the genome which will allow designing association studies and population surveys. Analysis of the genome-wide genetic diversity in P. vivax also reveals considerable allele sharing among isolates from different continents. This observation could be consistent with a high level of gene flow among parasite strains distributed throughout the world. Conclusions Our study shows that it is feasible to perform whole genome sequencing of P. vivax field isolates and rigorously characterize the genetic diversity of this parasite. The catalogue of polymorphisms generated here will enable large-scale genotyping studies and contribute to a better understanding of P. vivax traits such as drug resistance or erythrocyte invasion, partially circumventing the lack of laboratory culture that has hampered vivax research for years.
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