PDF(Pubmed)
Abstract：
In Morocco, cutaneous leishmaniasis (CL) caused by Leishmania (L.) tropica is an important health problem. Despite the high incidence of CL in the country, the genomic heterogeneity of these parasites is still incompletely understood. In this study, we sequenced the genomes of 14 Moroccan isolates of L. tropica collected from confirmed cases of CL to investigate their genomic heterogeneity. Comparative genomics analyses were conducted by applying the recently established Genome Instability Pipeline (GIP), which allowed us to conduct phylogenomic and principal components analyses (PCA), and to assess genomic variations at the levels of the karyotype, gene copy number, single nucleotide polymorphisms (SNPs) and small insertions/deletions (INDELs) variants. Read-depth analyses revealed a mostly disomic karyotype, with the exception of the stable tetrasomy of chromosome 31. In contrast, we identified important gene copy number variations across all isolates, which affect known virulence genes and thus were probably selected in the field. SNP-based cluster analysis of the 14 isolates revealed a core group of 12 strains that formed a tight cluster and shared 45.1 % (87 751) of SNPs, as well as two strains (M3015, Ltr_16) that clustered separately from each other and the core group, suggesting the circulation of genetically highly diverse strains in Morocco. Phylogenetic analysis, which compared our 14 L. tropica isolates against 40 published genomes of L. tropica from a diverse array of locations, confirmed the genetic difference of our Moroccan isolates from all other isolates examined. In conclusion, our results indicate potential regional variations in SNP profiles that may differentiate Moroccan L. tropica from other L. tropica strains circulating in endemic countries in the Middle East. Our report paves the way for future research with a larger number of strains that will allow correlation of diverse phenotypes (resistance to treatments, virulence) and origins (geography, host species, year of isolation) to defined genomic signals such as gene copy number variations or SNP profiles that may represent interesting biomarker candidates.
摘要：
在摩洛哥,利什曼原虫引起的皮肤利什曼病（CL）（L.)热带是一个重要的健康问题。尽管CL在国内发病率很高,这些寄生虫的基因组异质性仍未完全了解。在这项研究中,我们对从确诊的CL病例中收集的14株摩洛哥热带乳杆菌的基因组进行了测序，以调查其基因组异质性。通过应用最近建立的基因组不稳定管道（GIP）进行比较基因组学分析，这使得我们能够进行系统基因组和主成分分析(PCA)，并在核型水平上评估基因组变异，基因拷贝数,单核苷酸多态性（SNP）和小插入/缺失（INDEL）变体。阅读深度分析揭示了一种主要是二组学的核型，除了31号染色体的稳定四体。相比之下,我们确定了所有分离株的重要基因拷贝数变异，影响已知的毒力基因，因此可能在该领域被选择。对14个分离株进行的基于SNP的聚类分析显示了12个菌株的核心组，这些菌株形成了紧密的簇，并共享了45.1％（87751）的SNP，以及两个菌株（M3015，Ltr_16），它们彼此和核心群分开聚集，表明摩洛哥遗传高度多样化的菌株的流通。系统发育分析,比较了我们的14个热带乳杆菌分离株与40个已发表的来自不同位置的热带乳杆菌基因组，证实了我们的摩洛哥分离株与所有其他检测分离株的遗传差异。总之,我们的结果表明SNP谱的潜在区域差异可能将摩洛哥热带乳杆菌与在中东流行国家传播的其他热带乳杆菌菌株区分开。我们的报告为将来研究更多的菌株铺平了道路，这些菌株将允许不同表型的相关性（对治疗的抗性，毒力)和起源(地理，宿主物种,分离年份）定义的基因组信号，例如可能代表感兴趣的生物标志物候选物的基因拷贝数变异或SNP谱。
