Search bioRxiv⌕ Search

bioRxiv · 10.1101/2025.04.26.650801

Characterizing Plasmodium falciparum genetic diversity and complexity of infections in clinical malaria infections in Western and Coastal Kenya using the poly-alpha microsatellite marker

Abstract

BackgroundGenotyping P. falciparum polymorphic merozoite genes to describe parasite genetic diversity and the complexity of malaria infections (COI) is routinely used to assess the effectiveness of malaria control interventions. They are also utilized in anti-malarial drug therapeutic efficacy studies (TES) to differentiate recrudescent parasites from new infections. However, these polymorphic genes are usually under selection. Therefore, neutral microsatellite markers are preferred as they are also easier to genotype. The current study investigated the genetic diversity and COI using the poly- microsatellite marker to provide background information on circulating genotypes before its applied to TES in Kenya. MethodologyDried blood spot (DBS) samples were obtained from 93 participants from a TES in Busia County in 2016 and 92 participants from a malaria monitoring study conducted in Kilifi in 2020. Genotyping of the poly- microsatellite was done by PCR, capillary electrophoresis and the fragment data analyzed using GeneMarker. ResultsAbout 96.7% and 87% of the samples from Busia and Kilifi, respectively, were successfully genotyped. The infections in Busia were mainly polyclonal (80%) with a significantly higher mean COI of 2.9 (p < 0.0001), while those in Kilifi were mostly monoclonal (52.5%) with a mean COI of 1.7. Despite on average a younger population and lower parasite density, both regions had similar expected heterozygosity (He) (Busia = 0.92; Kilifi = 0.90) while Busia recorded a slightly higher number of effective alleles (Ne) (Busia = 10.8; Kilifi = 9.3). ConclusionThe poly- microsatellite genotyping revealed high genetic diversity of malaria parasites in Busia and Kilifi. These findings define the genotypes (fragment sizes) observed in the two Kenyan populations, providing a proof of concept for the utility of poly- in TES studies as a molecular correction tool and for the evaluation of the effectiveness of malaria interventions in Kenya.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kimenyi, K. M., Achieng, N., Mgawe, C., Ndwiga, L., Oyier, L.. 2025-04-30. Characterizing Plasmodium falciparum genetic diversity and complexity of infections in clinical malaria infections in Western and Coastal Kenya using the poly-alpha microsatellite marker. https://doi.org/10.1101/2025.04.26.650801

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Large language model-based bibliometric evaluation of population descriptors in human genetics

As the use of population descriptors such as race, ethnicity, and ancestry have become increasingly common in modern genetics research, there have been growing calls to critically examine their use. Most notably, in 2023, the National Academies of Science, Engineering, and Medicine (NASEM) published a report titled Using Population Descriptors in Genetics and Genomics Research: A New Framework for an Evolving Field, which included eight specific and actionable recommendations for researchers to implement the ethical and accurate use of population descriptors in genetic research. Here, we use the 2023 NASEM report as a benchmark to analyze the use of population descriptors in genome-wide association studies (GWAS). We develop a general toolkit for large language model-based bibliometrics, operationalize the report's recommendations into an evaluation framework, and apply this framework to evaluate all 4,007 papers from the GWAS Catalog published between 2007 and 2025 with full text available on PubMedCentral. We find significant improvements in adherence to NASEM report recommendations over time. However, most improvements predate the publication of the NASEM report itself, suggesting the report functioned primarily as a synthesis of existing best practices rather than a catalyst for change. We conclude by highlighting opportunities for growth in the field of human genetics.

genetics↗

Mitigating biases of rescaling in forward-in-time population genetic simulations

Forward-in-time population genetic simulations are widely used in evolutionary analyses, but simulating large populations and long genomic regions remains computationally demanding. To reduce this cost, parameter rescaling is widely employed, in which the original evolutionary process is approximated by one with a smaller population size and fewer generations. Recently, several studies using the SLiM simulator have raised concerns about the accuracy of this rescaling approach. In this study, we show that many of the biases reported in these studies can be mitigated by using a different simulation algorithm. These results reveal that the accuracy of parameter rescaling depends on how well the simulation algorithm preserves diffusion-limit properties under rescaling.

genetics↗

OPA1 controls mitochondrial dysfunction-driven liver fibrosis in MASLD

Progressive hepatic fibrosis is the principal determinant of morbidity and mortality in metabolic dysfunction-associated steatotic liver disease and steatohepatitis (MASLD/MASH). Mitochondrial dysfunction is a hallmark of MASH, and the release of mitochondrial damage-associated molecular patterns (mito-DAMPs) from injured hepatocytes can promote fibrosis. However, how mitochondrial dynamics and quality control shape the fibrotic response in MASLD/MASH remains unclear. Here, through large-scale genomic analyses of mitochondrial genes governing mitophagy, fusion and fission in human MASLD, with a power-equivalent sample size of approximately 700,000 individuals, we identify a strong association between hepatic fibrosis and the mitochondrial fusion factor dynamin-like GTPase optic atrophy 1 (OPA1). OPA1 transcripts and protein abundance in the liver epithelium were progressively dysregulated with advancing fibrosis. In mice, hepatocyte-specific OPA1 loss alone was sufficient to induce hepatic stellate cell activation and fibrosis in zone 3, promoted the release of mito-DAMPs into the circulation and exacerbated fibrosis in experimental MASH. These findings identify OPA1 as a central regulator of the hepatic fibrotic response and connect defective mitochondrial homeostasis to mito-DAMP release, hepatic stellate cell activation and fibrosis in MASLD.

genetics↗