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对来自不同海拔流行地区的恶性疟原虫中选定疫苗候选抗原和微卫星位点的基因多态性分析。

Analysis of genetic polymorphism in select vaccine candidate antigens and microsatellite loci in Plasmodium falciparum from endemic areas at varying altitudes.

作者信息

Mlambo Godfree, Sullivan David, Mutambu Susan L, Soko White, Mbedzi Joel, Chivenga James, Jaenisch Thomas, Gemperli Armin, Kumar Nirbhay

机构信息

Malaria Research Institute, Department of Molecular Microbiology and Immunology, Johns Hopkins University, Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, United States.

出版信息

Acta Trop. 2007 Jun;102(3):201-5. doi: 10.1016/j.actatropica.2007.05.001. Epub 2007 May 22.

Abstract

Plasmodium falciparum parasites obtained from symptomatic patients attending clinics in Bindura (altitude 1100 m), Chiredzi (600 m) and Kariba (<600 m), previously reported to differ in malaria endemicity were genotyped on the msp-1, msp-2 and glurp loci to examine the extent of parasite genetic diversity. While the parasites were monomorphic for msp-1 allele RO33 from the three locations, the K1 allele was over-represented in Kariba (p=0.02) and Mad20 alleles occurred at a higher frequency in Bindura. A similar PCR analysis for glurp and the two main allelic families of msp-2, i.e. IC/3D7 and FC-27 revealed minimal differences in the parasite population. A total of 8 msp-1 Block 2 and 11 msp-2 genotypes were identified from the three locations combined. On the glurp locus, 13 different genotypes ranging in size from 660 to 1160 bp were detected in parasites obtained from Bindura and Kariba. To gain further insight into P. falciparum genetic diversity in the three different geographical locations, parasites were examined for neutral microsatellite markers (C4M8, C13M30 and TA81). The number of microsatellite alleles ranged from 8 to 17 and the average expected heterozygosity (HE) for the three areas combined was 0.83 suggesting that the parasite population of Zimbabwe is genetically heterogeneous. These findings have implications in understanding the impact of genetic variation on immunity and possibly emergence of drug resistance.

摘要

从宾杜拉(海拔1100米)、奇雷兹(600米)和卡里巴(<600米)诊所的有症状患者身上获取的恶性疟原虫寄生虫,之前报道这些地区疟疾流行程度不同,对其msp-1、msp-2和glurp基因座进行基因分型,以检查寄生虫遗传多样性的程度。虽然来自这三个地点的寄生虫msp-1等位基因RO33是单态的,但K1等位基因在卡里巴占比过高(p=0.02),而Mad20等位基因在宾杜拉出现的频率更高。对glurp以及msp-2的两个主要等位基因家族即IC/3D7和FC-27进行的类似PCR分析显示,寄生虫群体中差异极小。从这三个地点总共鉴定出8种msp-1第2区和11种msp-2基因型。在glurp基因座上,从宾杜拉和卡里巴获取的寄生虫中检测到13种大小在660至1160 bp之间的不同基因型。为了进一步了解这三个不同地理位置的恶性疟原虫遗传多样性,对寄生虫进行了中性微卫星标记(C4M8、C13M30和TA81)检测。微卫星等位基因数量从8到17不等,三个地区合并后的平均预期杂合度(HE)为0.83,这表明津巴布韦的寄生虫群体在遗传上是异质的。这些发现对于理解遗传变异对免疫力的影响以及可能出现的耐药性具有重要意义。

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