{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T16:32:07Z","timestamp":1740155527934,"version":"3.37.3"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009950","name":"Ministry of Education","doi-asserted-by":"publisher","award":["KKU-420"],"award-info":[{"award-number":["KKU-420"]}],"id":[{"id":"10.13039\/100009950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Tropical Medicine"],"published-print":{"date-parts":[[2022,3,28]]},"abstract":"<jats:p>Background. Malaria is still a public health problem in Saudi Arabia specifically in the Jazan region. Plasmodium falciparum knob-associated histidine-rich proteins (PfKAHRPs) play an important role in cerebral malaria pathophysiology as well as pathogenesis of P. falciparum infections. The repeat region of PfKAHRP C-terminal interaction domain has been found to bind to the infected red blood cells and the vascular endothelium. Thus, this study aimed to assess the allelic variations, genetic diversity, and natural selection acting at the C-terminal PfKAHRP between parasite isolates from Saudi Arabia. Materials and Methods. The PfKHARP C-terminal interaction domain was successfully PCR-amplified and sequence data from 441 clinical isolates from Saudi Arabia were obtained. The DnaSP v5.10 software was used to determine the genetic diversity, polymorphism, haplotype, and natural selection. Haplotype network analysis was constructed by using the median-joining method in the NETWORK version 5.0.0.1 software. Results. Alignment and analysis of 441 C-terminal PfKAHRP-deduced amino acid sequences identified 5 genotypes (I\u2013V) based on the decapeptide repeat arrangements (TKEASTSKEA, TKEASTSKGA, TKEASTTEGA, and TKEASTSKRA). Among the repeat types, Type I (49.43%, 218\/441) was the most abundant in Saudi Arabia, followed by Type II (48.29%, 213\/441). Overall, the nucleotide diversity in the PfKHARP C-terminal region was found to be low in Saudi Arabia (\u03c0\u2009=\u20090.00142); however, natural selection tests indicated positive selection (dN-dS\u2009=\u20091.64, <jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mi>P<\/a:mi>\n                        <a:mo>&lt;<\/a:mo>\n                        <a:mn>0.05<\/a:mn>\n                     <\/a:math>\n                  <\/jats:inline-formula>) which was due to the variations within the repeat motifs. Genealogical relationship haplotype network of PfKAHRP from 4 different countries (i.e., Saudi Arabia, Iran, Burundi, and India) revealed 1 major shared haplotype cluster (H_1) with samples representative from all 4 countries (Saudi Arabia; n\u2009=\u2009441, Burundi; n\u2009=\u20094, Iran; n\u2009=\u200913, and India; n\u2009=\u20091). Conclusion. Since this is the first study to report on genetic diversity of C-terminal PfKAHRP interaction domain and the repeat motifs from clinical samples in Saudi Arabia, it will contribute towards the rational design of antiadhesion drug therapies for P. falciparum malaria.<\/jats:p>","DOI":"10.1155\/2022\/3740889","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T17:35:06Z","timestamp":1648488906000},"page":"1-6","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Diversity, Repeat Motifs, and Natural Selection at the C-Terminal Knob-Associated Histidine Rich Protein (KAHRP) of Plasmodium falciparum Clinical Samples from Saudi Arabia"],"prefix":"10.1155","volume":"2022","author":[{"given":"Saad M.","family":"Bin Dajem","sequence":"first","affiliation":[{"name":"Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3407-7220","authenticated-orcid":true,"given":"Md Atique","family":"Ahmed","sequence":"additional","affiliation":[{"name":"ICMR-Regional Medical Research Center, Dibrugarh, Assam, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Fe F Bohol","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9524-4128","authenticated-orcid":true,"given":"Syeda Wasfeea","family":"Wazid","sequence":"additional","affiliation":[{"name":"Arogyo Society of Health, Welfare and Support (ASHWAS), Dibrugarh, Assam, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed I.","family":"Shafeai","sequence":"additional","affiliation":[{"name":"Sabya General Hospital, Sabya, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuad H.","family":"Rudiny","sequence":"additional","affiliation":[{"name":"Sabya General Hospital, Sabya, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali M.","family":"Motaen","sequence":"additional","affiliation":[{"name":"Sabya General Hospital, Sabya, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kareem","family":"Morsy","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0132-558X","authenticated-orcid":true,"given":"Hani","family":"Alothaid","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4584-5739","authenticated-orcid":true,"given":"Ahmed A.","family":"Al-Qahtani","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia"},{"name":"Department of Microbiology and Immunology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-021-03846-4"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-018-2438-7"},{"volume-title":"Ministry of Health","year":"2018","author":"M. o. 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