Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing

Article

关键词: PAPUA-NEW-GUINEA;    MALARIA PARASITE;    LIBRARY PREPARATION;    GENOME;    RESISTANCE;    TRANSMISSION;    POLYMORPHISM;    EVOLUTION;    SELECTION;    PATTERNS;   

DOI  :  10.1038/nature11174

来源: SCIE

【 摘 要 】

Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance(1,2). Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P. falciparum genome.

【 授权许可】

Free