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Parasitol."],"abstract":"<jats:p>The enormous diversity and complexity of <jats:italic>var<\/jats:italic> 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 <jats:italic>var<\/jats:italic> genes is to use a small \u2018tag\u2019 region encoding the immunogenic DBL\u03b1 domain as a marker to estimate <jats:italic>var<\/jats:italic> diversity. As <jats:italic>var<\/jats:italic> genes diversify by recombination, it is not clear the extent to which the same tag can appear in multiple <jats:italic>var<\/jats:italic> genes. This relationship between marker and gene has not been investigated in natural populations. Analyses of <jats:italic>in vitro<\/jats:italic> recombination within and between <jats:italic>var<\/jats:italic> genes have suggested that this relationship would not be exclusive. Using a dataset of publicly-available assembled <jats:italic>var<\/jats:italic> sequences, we test this hypothesis by studying DBL\u03b1-<jats:italic>var<\/jats:italic> 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, DBL\u03b1-<jats:italic>var<\/jats:italic> relationships were shown to be predominantly 1-to-1, followed by a second largest proportion of 1-to-2 DBL\u03b1-<jats:italic>var<\/jats:italic> relationships. This finding indicates that DBL\u03b1 tags can be used to estimate not just DBL\u03b1 diversity but <jats:italic>var<\/jats:italic> gene diversity when applied in a local endemic area. Epidemiological applications of this result are discussed.<\/jats:p>","DOI":"10.3389\/fpara.2022.1006341","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T13:40:53Z","timestamp":1673358053000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Unravelling var complexity: Relationship between DBL\u03b1 types and var genes in Plasmodium falciparum"],"prefix":"10.3389","volume":"1","author":[{"given":"Mun Hua","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heejung","family":"Shim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-ban","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen P.","family":"Day","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.gene.2010.01.001","article-title":"The south American Plasmodium falciparum var gene repertoire is limited, highly shared and possibly lacks several antigenic types","volume":"453","author":"Albrecht","year":"2010","journal-title":"Gene"},{"key":"B2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.molbiopara.2006.07.007","article-title":"Extense variant gene family repertoire overlap in Western Amazon Plasmodium falciparum isolates","volume":"150","author":"Albrecht","year":"2006","journal-title":"Mol. 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