近日来自厦门大学生命科学学院、美国国立卫生研究院（NIH）等研究机构的研究人员在国际权威期刊《美国科学院院刊》(PNAS)上发表了题为“Linkage maps from multiple genetic crosses and loci linked to growth-related virulent phenotype in Plasmodium yoelii”的研究论文。在文章中，研究人员通过建立约氏疟原虫实验模型、使用遗传定位的方法鉴定了3个控制疟原虫与生长速度相关的毒力性状的基因座位。
文章的通讯作者为厦门大学生命科学学院长江学者讲座教授苏新专，厦门大学博士生李剑、朱峰以及NIH的Sittiporn Pattaradilokrat博士为这篇论文的共同第一作者。
疟疾是一种影响社会经济发展、危害人类健康的重要的寄生虫传染病，全球每年约有一百万人死于疟疾。由于疟疾有效疫苗的缺乏、以及耐药性蚊媒和抗药性疟原虫的出现和扩散，给当今疟疾的防治工作带来了极大的困难。
为了更好地研究疟疾疾病表现型的分子机制，研究人员构建了三个约氏疟原虫遗传杂交组，共进行了14次单独的遗传杂交实验，筛选出75个独立的重组克隆子代，并首次建立了高分辨率的约氏疟原虫遗传图谱。高分辨率遗传图谱的建立将为约氏疟原虫基因组序列的拼接和整合提供了一个坚实的染色体框架，也将为不同疟疾表型（如抗药性、寄生虫发育和致病性等）研究提供重要的研究工具。在鉴定的3个与生长速度相关的毒力性状的基因座位中，位于染色体13和染色体10的两个贡献座位与疟原虫的早期生长速度性状相连锁（感染后第5天）。染色体13的候选基因pyeb1的编码蛋白其R6结构域上C741Y的突变可能与约氏疟原虫致病性毒力和生长速度的改变有关。另外一个位于染色体7的基因座位连锁于寄生虫的晚期生长速度性状（感染后第10天）。鉴定与寄生虫生长速度和致病性相关的贡献作为将为最终鉴别出潜在的决定基因和进行疾病控制提供遗传学基础。 （生物谷Bioon.com）
生物谷推荐原文出处：
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.
