Next-Generation Analysis of Trypanosomatid Genome Stability and Instability

Briggs, Emma; Marques, Catarina A.; Reis-Cunha, João Luís; Black, Jennifer Ann; Campbell, Samantha J; Damasceno, Jeziel D.; Bartholomeu, Daniella Castanheira; Crouch, Kathryn; McCulloch, Richard

doi:10.1007/978-1-0716-0294-2_15

Cited by 2 publications

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References 26 publications

(33 reference statements)

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“…Previous attempts to use allele frequency to estimate somy of L . infantum were unsuccessful due to a low number of heterozygous SNPs in this parasite species [ 44 ]. Since L .…”

Section: Resultsmentioning

confidence: 99%

“…Leishmania parasites exhibit mosaic aneuploidy, and it has been suggested that modulating chromosomal copy number provides the parasite with a mechanism for regulating gene dosage in the absence of promoter-driven gene expression [42,43]. Previous attempts to use allele frequency to estimate somy of L. infantum were unsuccessful due to a low number of heterozygous SNPs in this parasite species [44]. Since L. braziliensis has been reported to have a higher number of SNPs than other Leishmania species [7], we tested whether the alternate allele read depth proportion (AARDP), as determined by SWGA, could be used to infer chromosome copy number.…”

Section: Somy Analysis With Swgamentioning

confidence: 99%

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Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies

et al. 2023

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In Brazil, Leishmania braziliensis is the main causative agent of the neglected tropical disease, cutaneous leishmaniasis (CL). CL presents on a spectrum of disease severity with a high rate of treatment failure. Yet the parasite factors that contribute to disease presentation and treatment outcome are not well understood, in part because successfully isolating and culturing parasites from patient lesions remains a major technical challenge. Here we describe the development of selective whole genome amplification (SWGA) for Leishmania and show that this method enables culture-independent analysis of parasite genomes obtained directly from primary patient skin samples, allowing us to circumvent artifacts associated with adaptation to culture. We show that SWGA can be applied to multiple Leishmania species residing in different host species, suggesting that this method is broadly useful in both experimental infection models and clinical studies. SWGA carried out directly on skin biopsies collected from patients in Corte de Pedra, Bahia, Brazil, showed extensive genomic diversity. Finally, as a proof-of-concept, we demonstrated that SWGA data can be integrated with published whole genome data from cultured parasite isolates to identify variants unique to specific geographic regions in Brazil where treatment failure rates are known to be high. SWGA provides a relatively simple method to generate Leishmania genomes directly from patient samples, unlocking the potential to link parasite genetics with host clinical phenotypes.

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“…Previous attempts to use allele frequency to estimate somy of L . infantum were unsuccessful due to a low number of heterozygous SNPs in this parasite species [ 44 ]. Since L .…”

Section: Resultsmentioning

confidence: 99%

Section: Somy Analysis With Swgamentioning

confidence: 99%

Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies

et al. 2023

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Selective whole-genome amplification reveals population genetics ofLeishmania braziliensisdirectly from patient skin biopsies

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Reis-Cunha

et al. 2022

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In Brazil, Leishmania braziliensis is the main causative agent of the neglected tropical disease, cutaneous leishmaniasis (CL). CL caused by L. braziliensis can present on a spectrum of disease severity with high rate of treatment failure. Yet the parasite factors that may contribute to disease presentation and treatment outcome are not well understood, in part because successfully isolating and culturing parasites from patient lesions remains a major technical challenge. Here we describe the development of selective whole genome amplification (SWGA) for Leishmania and show that this method enables culture-independent analysis of parasite genomes obtained directly from primary patient skin samples, allowing us to circumvent artifacts associated with adaptation to culture. We show that SWGA can be applied to multiple Leishmania species residing in different host species, suggesting that this method is broadly useful in both experimental infection models and clinical studies. Finally, we show that parasite genome sequencing data generated by SWGA of skin biopsies collected from patients in Corte de Pedra, Bahia, Brazil exhibit substantial genetic diversity and can be integrated with published whole genome data from parasite isolates to identify variants associated with high treatment failure rates observed in Northeast Brazil.

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Next-Generation Analysis of Trypanosomatid Genome Stability and Instability

Cited by 2 publications

References 26 publications

Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies

Selective whole-genome amplification reveals population genetics of Leishmania braziliensis directly from patient skin biopsies

Selective whole-genome amplification reveals population genetics ofLeishmania braziliensisdirectly from patient skin biopsies

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