Long term persistence of clonal malaria parasite Plasmodium falciparum lineages in the Colombian Pacific region

BMC Genetics

Tim JC Anderson³  Claribel Murillo⁴  Sanjay Menon¹  Lyda Osorio²  Shalini Nair³  Diego F Echeverry⁴ 

[1] Virginia Commonwealth University, Richmond, VA, 23220, USA;Grupo de Epidemiología y Salud Poblacional, GESP, School of Public Health, Faculty of Health, Universidad del Valle, Calle 4B # 36-00, Cali, Colombia;Department of Genetics, Texas Biomedical Research Institute, 7620 NW Loop 410, San Antonio, Texas, USA;International Center for Medical Research and Training, CIDEIM, Carrera 125 # 19-225 Av. La María, Cali, Colombia

关键词: Association studies;    Linkage disequilibrium;    SNPs;    Population structure;    Genotypic richness;    Persistence;    Relatedness;    Clonality;    Colombia;    Plasmodium falciparum;   

Others  :  1089671
DOI  :  10.1186/1471-2156-14-2

 received in 2012-09-20, accepted in 2012-12-21,  发布年份 2013

【 摘 要 】

Background

Resistance to chloroquine and antifolate drugs has evolved independently in South America, suggesting that genotype - phenotype studies aimed at understanding the genetic basis of resistance to these and other drugs should be conducted in this continent. This research was conducted to better understand the population structure of Colombian Plasmodium falciparum in preparation for such studies.

Results

A set of 384 SNPs were genotyped in blood spot DNA samples from 447 P. falciparum infected subjects collected over a ten year period from four provinces of the Colombian Pacific coast to evaluate clonality, population structure and linkage disequilibrium (LD). Most infections (81%) contained a single predominant clone. These clustered into 136 multilocus genotypes (MLGs), with 32% of MLGs recovered from multiple (2 – 28) independent subjects. We observed extremely low genotypic richness (R = 0.42) and long persistence of MLGs through time (median = 537 days, range = 1 – 2,997 days). There was a high probability (>5%) of sampling parasites from the same MLG in different subjects within 28 days, suggesting caution is needed when using genotyping methods to assess treatment success in clinical drug trials. Panmixia was rejected as four well differentiated subpopulations (F_ST = 0.084 - 0.279) were identified. These occurred sympatrically but varied in frequency within the four provinces. Linkage disequilibrium (LD) decayed more rapidly (r² = 0.17 for markers <10 kb apart) than observed previously in South American samples.

Conclusions

We conclude that Colombian populations have several advantages for association studies, because multiple clone infections are uncommon and LD decays over the scale of one or a few genes. However, the extensive population structure and low genotype richness will need to be accounted for when designing and analyzing association studies.

【 授权许可】

   
2013 Echeverry et al.; licensee BioMed Central Ltd.

【 图 表 】

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