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氯喹抗性疟疾的遗传学:单倍型视角

Genetics of chloroquine-resistant malaria: a haplotypic view.

作者信息

Awasthi Gauri, Das Aparup

出版信息

Mem Inst Oswaldo Cruz. 2013 Dec;108(8):947-61. doi: 10.1590/0074-0276130274.

DOI:10.1590/0074-0276130274
PMID:24402147
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4005552/
Abstract

The development and rapid spread of chloroquine resistance (CQR) in Plasmodium falciparum have triggered the identification of several genetic target(s) in the P. falciparum genome. In particular, mutations in the Pfcrt gene, specifically, K76T and mutations in three other amino acids in the region adjoining K76 (residues 72, 74, 75 and 76), are considered to be highly related to CQR. These various mutations form several different haplotypes and Pfcrt gene polymorphisms and the global distribution of the different CQR- Pfcrt haplotypes in endemic and non-endemic regions of P. falciparum malaria have been the subject of extensive study. Despite the fact that the Pfcrt gene is considered to be the primary CQR gene in P. falciparum , several studies have suggested that this may not be the case. Furthermore, there is a poor correlation between the evolutionary implications of the Pfcrt haplotypes and the inferred migration of CQR P. falciparum based on CQR epidemiological surveillance data. The present paper aims to clarify the existing knowledge on the genetic basis of the different CQR- Pfcrt haplotypes that are prevalent in worldwide populations based on the published literature and to analyse the data to generate hypotheses on the genetics and evolution of CQR malaria.

摘要

恶性疟原虫中氯喹抗性(CQR)的发展和迅速传播引发了对恶性疟原虫基因组中几个遗传靶点的鉴定。特别是,Pfcrt基因中的突变,具体而言,K76T以及K76附近区域(残基72、74、75和76)的其他三个氨基酸的突变,被认为与CQR高度相关。这些不同的突变形成了几种不同的单倍型和Pfcrt基因多态性,并且不同CQR - Pfcrt单倍型在恶性疟原虫疟疾流行和非流行地区的全球分布一直是广泛研究的主题。尽管Pfcrt基因被认为是恶性疟原虫中主要的CQR基因,但一些研究表明情况可能并非如此。此外,基于CQR流行病学监测数据,Pfcrt单倍型的进化意义与推断的CQR恶性疟原虫迁移之间的相关性较差。本文旨在根据已发表的文献阐明全球人群中普遍存在的不同CQR - Pfcrt单倍型的遗传基础方面的现有知识,并分析数据以生成关于CQR疟疾的遗传学和进化的假设。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/4005552/4983c1723a11/0074-0276-mioc-108-8-0947-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/4005552/2562e8aea3cd/0074-0276-mioc-108-8-0947-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/4005552/4983c1723a11/0074-0276-mioc-108-8-0947-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/4005552/2562e8aea3cd/0074-0276-mioc-108-8-0947-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/4005552/4983c1723a11/0074-0276-mioc-108-8-0947-gf02.jpg

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