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Unravelling var complexity: Relationship between DBLα types and var genes in Plasmodium falciparum

The enormous diversity and complexity of var genes that diversify rapidly by recombination has led to the exclusion of assembly of these genes from major genome initiatives (e.g., Pf6). A scalable solution in epidemiological surveillance of var genes is to use a small ‘tag’ region encoding the immun...

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Autores principales: Tan, Mun Hua, Shim, Heejung, Chan, Yao-ban, Day, Karen P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060044/
https://www.ncbi.nlm.nih.gov/pubmed/36998722
http://dx.doi.org/10.3389/fpara.2022.1006341
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author Tan, Mun Hua
Shim, Heejung
Chan, Yao-ban
Day, Karen P.
author_facet Tan, Mun Hua
Shim, Heejung
Chan, Yao-ban
Day, Karen P.
author_sort Tan, Mun Hua
collection PubMed
description The enormous diversity and complexity of var genes that diversify rapidly by recombination has led to the exclusion of assembly of these genes from major genome initiatives (e.g., Pf6). A scalable solution in epidemiological surveillance of var genes is to use a small ‘tag’ region encoding the immunogenic DBLα domain as a marker to estimate var diversity. As var genes diversify by recombination, it is not clear the extent to which the same tag can appear in multiple var genes. This relationship between marker and gene has not been investigated in natural populations. Analyses of in vitro recombination within and between var genes have suggested that this relationship would not be exclusive. Using a dataset of publicly-available assembled var sequences, we test this hypothesis by studying DBLα-var relationships for four study sites in four countries: Pursat (Cambodia) and Mae Sot (Thailand), representing low malaria transmission, and Navrongo (Ghana) and Chikwawa (Malawi), representing high malaria transmission. In all study sites, DBLα-var relationships were shown to be predominantly 1-to-1, followed by a second largest proportion of 1-to-2 DBLα-var relationships. This finding indicates that DBLα tags can be used to estimate not just DBLα diversity but var gene diversity when applied in a local endemic area. Epidemiological applications of this result are discussed.
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spelling pubmed-100600442023-03-29 Unravelling var complexity: Relationship between DBLα types and var genes in Plasmodium falciparum Tan, Mun Hua Shim, Heejung Chan, Yao-ban Day, Karen P. Front Parasitol Article The enormous diversity and complexity of var genes that diversify rapidly by recombination has led to the exclusion of assembly of these genes from major genome initiatives (e.g., Pf6). A scalable solution in epidemiological surveillance of var genes is to use a small ‘tag’ region encoding the immunogenic DBLα domain as a marker to estimate var diversity. As var genes diversify by recombination, it is not clear the extent to which the same tag can appear in multiple var genes. This relationship between marker and gene has not been investigated in natural populations. Analyses of in vitro recombination within and between var genes have suggested that this relationship would not be exclusive. Using a dataset of publicly-available assembled var sequences, we test this hypothesis by studying DBLα-var relationships for four study sites in four countries: Pursat (Cambodia) and Mae Sot (Thailand), representing low malaria transmission, and Navrongo (Ghana) and Chikwawa (Malawi), representing high malaria transmission. In all study sites, DBLα-var relationships were shown to be predominantly 1-to-1, followed by a second largest proportion of 1-to-2 DBLα-var relationships. This finding indicates that DBLα tags can be used to estimate not just DBLα diversity but var gene diversity when applied in a local endemic area. Epidemiological applications of this result are discussed. 2022 2023-01-09 /pmc/articles/PMC10060044/ /pubmed/36998722 http://dx.doi.org/10.3389/fpara.2022.1006341 Text en https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Article
Tan, Mun Hua
Shim, Heejung
Chan, Yao-ban
Day, Karen P.
Unravelling var complexity: Relationship between DBLα types and var genes in Plasmodium falciparum
title Unravelling var complexity: Relationship between DBLα types and var genes in Plasmodium falciparum
title_full Unravelling var complexity: Relationship between DBLα types and var genes in Plasmodium falciparum
title_fullStr Unravelling var complexity: Relationship between DBLα types and var genes in Plasmodium falciparum
title_full_unstemmed Unravelling var complexity: Relationship between DBLα types and var genes in Plasmodium falciparum
title_short Unravelling var complexity: Relationship between DBLα types and var genes in Plasmodium falciparum
title_sort unravelling var complexity: relationship between dblα types and var genes in plasmodium falciparum
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060044/
https://www.ncbi.nlm.nih.gov/pubmed/36998722
http://dx.doi.org/10.3389/fpara.2022.1006341
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