1. Leishmania braziliensis causing human disease in Northeast Brazil presents loci with genotypes in long-term equilibrium.
- Author
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Silva, Juliana A., Pinheiro, Ana Isabelle, Dourado, Maria Luiza, Medina, Lilian, Queiroz, Adriano, Guimarães, Luiz Henrique, Lessa, Marcus Miranda, Lago, Ednaldo L., Machado, Paulo Roberto L., Wilson, Mary E., Carvalho, Edgar M., and Schriefer, Albert
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LOCUS (Genetics) ,GENOTYPES ,GENETIC recombination ,POPULATION genetics ,LEISHMANIA - Abstract
Background: Leishmaniases are neglected tropical diseases that inflict great burden to poor areas of the globe. Intense research has aimed to identify parasite genetic signatures predictive of infection outcomes. Consistency of diagnostic tools based on these markers would greatly benefit from accurate understanding of Leishmania spp. population genetics. We explored two chromosomal loci to characterize a population of L. braziliensis causing human disease in Northeast Brazil. Methodology/Principal findings: Two temporally distinct samples of L. braziliensis were obtained from patients attending the leishmaniasis clinic at the village of Corte de Pedra: (2008–2011) primary sample, N = 120; (1999–2001) validation sample, N = 35. Parasites were genotyped by Sanger's sequencing of two 600 base pairs loci starting at nucleotide positions 3,074 and 425,451 of chromosomes 24 and 28, respectively. Genotypes based on haplotypes of biallelic positions in each locus were tested for several population genetic parameters as well as for geographic clustering within the region. Ample geographic overlap of genotypes at the two loci was observed as indicated by non-significant Cusick and Edward's comparisons. No linkage disequilibrium was detected among combinations of haplotypes for both parasite samples. Homozygous and heterozygous genotypes displayed Hardy-Weinberg equilibrium (HWE) at both loci in the two samples when straight observed and expected counts were compared by Chi-square (p>0.5). However, Bayesian statistics using one million Monte-Carlo randomizations disclosed a less robust HWE for chromosome 24 genotypes, particularly in the primary sample (p = 0.04). Fixation indices (Fst) were consistently lower than 0.05 among individuals of the two samples at both tested loci, and no intra-populational structuralization could be detected using STRUCTURE software. Conclusions/Significance: These findings suggest that L. braziliensis can maintain stable populations in foci of human leishmaniasis and are capable of robust genetic recombination possibly due to events of sexual reproduction during the parasite's lifecycle. Author summary: Leishmania braziliensis affects poor human populations in the tropics, may cause face disfiguring lesions and may also resist treatment. There has been intense research for markers in these parasites genetic contents for helping predict if an infected human being would be of greater chance of severe disease or treatment failure. The consistent identification of such markers requires a deep understanding of how genes circulate within these parasites' natural populations. We explored two small segments of DNA (i.e. loci), one on chromosome 24, the other on chromosome 28 of L. braziliensis to characterize a population that causes human disease in Northeast Brazil. We employed two samples of parasites obtained from lesions of patients diagnosed from 1999 to 2001, and from 2008 to 2011. We sequenced the DNA of those loci in each parasite of the two samples. Then, we evaluated the status of several population genetics parameters among them. Based on our findings to that region, we concluded that L. braziliensis can maintain populations that are genetically stable for several years in foci of human leishmaniasis and are capable of robust recombination of their genetic contents, probably due to events of sexual reproduction during its lifecycle. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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