Abstract
Background: There are several techniques to analyse copy number variation in both research and clinical settings, such as whole genome amplification (sWGA), SNP arrays and one of the most commonly used techniques, array based comparative genomic hybridization (aCGH). In the latter, copy number comparison is obtained between differentially labelled target and reference DNAs by measuring ratio of fluorescence intensity of probes indicating loss or gain in the chromosomal region. Methods: Here we carry out a comparative analysis between two Plasmodium falciparum parasite isolates (Pf-isolate-2 and Pf-isolate-1) causing malaria using array CGH. The array contains approximately 418,577, 60mer custom-designed probes with an average probe spacing of 56 bp. The significant major variations (amplifications and deletions) copy number variations (CNV) in Pf-isolate-2 (Pf-2) in comparison with Pf-isolate-1 (Pf-1), are reported. Results: CNVs have been seen in all the chromosomes in Pf-2, most of the deletions have been seen mostly in sub-telomeric and telomeric regions of the chromosomes that comprises of variant surface antigen family genes. Apart from the subtelomeric regions other parts of the chromosomes have also shown CNVs. Novel variations , like continuous amplification of 28kb region (249817-278491) of chromosome-8, which covers for 3 genes two of which codes for conserved Plasmodium proteins with unknown function (MAL8P1.139, PF08_0122) and tRNA pseudouridine synthase, putative (PF08_0123). Amplifications in regions harboring genes like GTP cyclohydrolase I (GCH-1, PFL1155W) and ribosomal protein, L24, putative (PFL1150C) of chromosome 12 were seen. Conclusion: Other than known variations reported earlier, some novel variations have also been seen in the chromosomes of Pf-2. This is an experimental case study reporting major amplifications and deletions in Pf-isolate-2 in comparison with Pf-isolate-1 using a tiling array based comparative genomic hybridization approach.
Highlights
Plasmodium falciparum is the most virulent among the 6 Plasmodium species that causes malaria in humans
In this study, a custom designed tiling microarray has been used to investigate the overall difference between the two clinical isolates i.e., Pf-isolate-2 (Pf-2) and Pf-isolate-1 (Pf-1)
The tiling array used in this study enables large-scale detection of regions showing copy number variations across the whole genome
Summary
Plasmodium falciparum is the most virulent among the 6 Plasmodium species that causes malaria in humans. Along with the exported family members, these genes play an important role in cytoadhesion by binding to multiple cell receptors, including ICAM-1, CD36, E-selectin, NCAM and CD31 on micro vascular endothelia, which mediates sequestration that in-turn, leads to the severity of the disease. Another receptor, Endothelial protein C receptor (EPCR), a brain specific receptor has been identified as a binding partner of PfEMP-1 (Smith et al, 2013; Wassmer & Gray, 2017).
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