近日來自廈門大學生命科學學院、美國國立衛生研究院（NIH）等研究機構的研究人員在國際權威期刊《美國科學院院刊》(PNAS)上發表了題為「Linkage maps from multiple genetic crosses and loci linked to growth-related virulent phenotype in Plasmodium yoelii」的研究論文。在文章中，研究人員通過建立約氏瘧原蟲實驗模型、使用遺傳定位的方法鑑定了3個控制瘧原蟲與生長速度相關的毒力性狀的基因座位。
文章的通訊作者為廈門大學生命科學學院*講座教授蘇新專，廈門大學博士生李劍、朱峰以及NIH的Sittiporn Pattaradilokrat博士為這篇論文的共同第一作者。
瘧疾是一種影響社會經濟發展、危害人類健康的重要的寄生蟲傳染病，全球每年約有一百萬人死於瘧疾。由於瘧疾有效疫苗的缺乏、以及耐藥性蚊媒和抗藥性瘧原蟲的出現和擴散，給當今瘧疾的防治工作帶來了極大的困難。
為了更好地研究瘧疾疾病表現型的分子機制，研究人員構建了三個約氏瘧原蟲遺傳雜交組，共進行了14次單獨的遺傳雜交實驗，篩選出75個獨立的重組克隆子代，並首次建立了高解析度的約氏瘧原蟲遺傳圖譜。高解析度遺傳圖譜的建立將為約氏瘧原蟲基因組序列的拼接和整合提供了一個堅實的染色體框架，也將為不同瘧疾表型（如抗藥性、寄生蟲發育和致病性等）研究提供重要的研究工具。在鑑定的3個與生長速度相關的毒力性狀的基因座位中，位於染色體13和染色體10的兩個貢獻座位與瘧原蟲的早期生長速度性狀相連鎖（感染後第5天）。染色體13的候選基因pyeb1的編碼蛋白其R6結構域上C741Y的突變可能與約氏瘧原蟲致病性毒力和生長速度的改變有關。另外一個位於染色體7的基因座位連鎖於寄生蟲的晚期生長速度性狀（感染後第10天）。鑑定與寄生蟲生長速度和致病性相關的貢獻作為將為最終鑑別出潛在的決定基因和進行疾病控制提供遺傳學基礎。 （生物谷Bioon.com）
生物谷推薦原文出處：
The Proceedings of the National Academy of Sciences doi: 10.1073/pnas.1102261108
Linkage maps from multiple genetic crosses and loci linked to growth-related virulent phenotype in Plasmodium yoelii
Jian Li, Sittiporn Pattaradilokrat, Feng Zhua,, Hongying Jiang, Shengfa Liu, Lingxian Hong, Yong Fu, Lily Koo, Wenyue Xu, Weiqing Pan, Jane M. Carlton, Osamu Kaneko, Richard Carter, John C. Wootton, and Xin-zhuan Su
Plasmodium yoelii is an excellent model for studying malaria pathogenesis that is often intractable to investigate using human parasites; however, genetic studies of the parasite have been hindered by lack of genome-wide linkage resources. Here, we performed 14 genetic crosses between three pairs of P. yoelii clones/subspecies, isolated 75 independent recombinant progeny from the crosses, and constructed a high-resolution linkage map for this parasite. Microsatellite genotypes from the progeny formed 14 linkage groups belonging to the 14 parasite chromosomes, allowing assignment of sequence contigs to chromosomes. Growth-related virulent phenotypes from 25 progeny of one of the crosses were significantly associated with a major locus on chromosome 13 and with two secondary loci on chromosomes 7 and 10. The chromosome 10 and 13 loci are both linked to day 5 parasitemia, and their effects on parasite growth rate are independent but additive. The locus on chromosome 7 is associated with day 10 parasitemia. The chromosome 13 locus spans ～220 kb of DNA containing 51 predicted genes, including the P. yoelii erythrocyte binding ligand, in which a C741Y substitution in the R6 domain is implicated in the change of growth rate. Similarly, the chromosome 10 locus spans ～234 kb with 71 candidate genes, containing a member of the 235-kDa rhoptry proteins (Py235) that can bind to the erythrocyte surface membrane. Atypical virulent phenotypes among the progeny were also observed. This study provides critical tools and information for genetic investigations of virulence and biology of P. yoelii.