Biology subjects

Lo, E.

Publications and source records attributed to Lo, E..

21 records · Page 2Linked to original sources

bioRxiv2020

Extensive genetic diversity in Plasmodium vivax from Sudan and its genetic relationships with other geographical isolates

Plasmodium vivax malaria is a neglected tropical disease in Africa due to low occurrence rates and lack of accurate diagnosis. Recently, there has been a dramatic increase in P. vivax cases in East Africa and reportedly spreading to western countries. This study investigated the geographical origin and genetic diversity of P. vivax in Sudan by 14 microsatellite markers. A total of 113 clinical P. vivax samples were collected from two districts, New Halfa and Khartoum in Sudan. In addition, data from 841 geographical samples retrieved from the database for global genetic analysis were included in the analysis to further the genetic relationships among the P. vivax isolates at regional and worldwide scales. On a regional scale, we observed 91 unique and 8 shared haplotypes amongst the Sudan samples. Such a high genetic diversity compared to other geographical isolates lends support to hypothesis that P. vivax was originated from Africa. On a global scale, as already demonstrated, we observed distinct genetic clustering of P. vivax isolates from Africa, South America, and Asia (including Papua New Guinea and Solomon Island) with limited admixture in all three clusters. The principal component analysis and phylogenetic tree showed similar clustering patterns and highlighted the contribution of the African isolates to the genetic variation observed globally. The East African P. vivax showed similarity with some of the Asian isolates suggesting potential recent introductions. Our results show extensive genetic diversity co-occurring with significant multi-locus linkage disequilibrium, demonstrating the effectiveness of using microsatellite markers to implement effective control measures.

genetics↗

bioRxiv2020

Whole Genome Sequencing of Plasmodium vivax Isolates Reveals Frequent Sequence and Structural Polymorphisms in Erythrocyte Binding Genes

Plasmodium vivax malaria is much less common in Africa than the rest of the world because the parasite relies primarily on the Duffy antigen/chemokine receptor (DARC) to invade human erythrocytes, and the majority of Africans are Duffy negative. Recently, there has been a dramatic increase in the reporting of P. vivax cases in Africa, with a high number of them being in Duffy negative individuals, potentially indicating P. vivax has evolved an alternative invasion mechanism that can overcome Duffy negativity. Here, we analyzed single nucleotide polymorphism (SNP) and copy number variation (CNV) in Whole Genome Sequence (WGS) data from 44 P. vivax samples isolated from symptomatic malaria patients in southwestern Ethiopia, where both Duffy positive and Duffy negative individuals are found. A total of 236,351 SNPs were detected, of which 21.9% was nonsynonymous and 78.1% was synonymous mutations. The largest number of SNPs were detected on chromosomes 9 (33,478 SNPs; 14% of total) and 10 (28,133 SNPs; 11.9%). There were particularly high levels of polymorphism in erythrocyte binding gene candidates including reticulocyte binding protein 2c (RBP2c), merozoite surface protein 1 (MSP1), and merozoite surface protein 3 (MSP3.5, MSP3.85 and MSP3.9). Thirteen genes related to immunogenicity and erythrocyte binding function were detected with significant signals of positive selection. Variation in gene copy number was also concentrated in genes involved in host-parasite interactions, including the expansion of the Duffy binding protein gene (PvDBP) on chromosome 6 and several PIR genes. Based on the phylogeny constructed from the whole genome sequences, the expansion of these genes was an independent process among the P. vivax lineages in Ethiopia. We further inferred transmission patterns of P. vivax infections among study sites and showed various levels of gene flow at a small geographical scale. The genomic features of P. vivax provided baseline data for future comparison with those in Duffy-negative individuals, and allowed us to develop a panel of informative Single Nucleotide Polymorphic markers diagnostic at a micro-geographical scale.

genomics↗

bioRxiv2019

Frequent expansion of Plasmodium vivax Duffy Binding Protein in Ethiopia and its epidemiological significance

Plasmodium vivax invasion of human erythrocytes depends on the Duffy Binding Protein (PvDBP) which interacts with the Duffy antigen. PvDBP copy number varies between P. vivax isolates, but the prevalence of PvDBP multiplications in Sub-Saharan Africa and its impact are unknown. We determined the prevalence and type of PvDBP duplications, as well as PvDBP copy number variation among 178 Ethiopian P. vivax isolates using a PCR-based diagnostic method, a novel quantitative real-time PCR assay and whole genome sequencing. For the 145 symptomatic samples, PvDBP duplications were detected in 95 isolates, of which 81 had the Cambodian and 14 Malagasy-type PvDBP duplications. PvDBP varied from 1 to >4 copies. Isolates with multiple PvDBP copies were found to be higher in symptomatic than asymptomatic infections. For the 33 asymptomatic samples, PvDBP was detected with two copies in two of the isolates, and both were the Cambodian-type PvDBP duplication. PvDBP copy number in Duffy-negative heterozygotes was not significantly different from that in Duffy-positives, providing no support for the hypothesis that increased copy number is a specific association with Duffy-negativity, although the number of Duffy-negatives was small and further sampling is required to test this association thoroughly. Author summaryPlasmodium vivax invasion of human erythrocytes relies on interaction between the Duffy antigen and P. vivax Duffy Binding Protein (PvDBP). Whole genome sequences from P. vivax field isolates in Madagascar identified a duplication of the PvDBP gene and PvDBP duplication has also been detected in non-African P. vivax-endemic countries. Two types of PvDBP duplications have been reported, termed Cambodian and Malagasy-type duplications. Our study used a combination of PCR-based diagnostic method, a novel quantitative real-time PCR assay, and whole genome sequencing to determine the prevalence and type of PvDBP duplications, as well as PvDBP copy number on a broad number of P. vivax samples in Ethiopia. We found that over 65% of P. vivax isolated from the symptomatic infections were detected with PvDBP duplications and PvDBP varied from 1 to >4 copies. The majority of PvDBP duplications belongs to the Cambodian-type while the Malagasy-type duplications was also detected. For the asymptomatic infections, despite a small sample size, the majority of P. vivax were detected with a single-copy based on both PCR and qPCR assays. There was no significant difference in PvDBP copy number between Duffy-null heterozygote and Duffy-positive homozygote/heterozygote. Further investigation is needed with expanded Duffy-null homozygotes to examine the functional significance of PvDBP expansion.

epidemiology↗