Linkage maps from multiple genetic crosses and loci linked to growth-related virulent phenotype in Plasmodium yoelii

Jian Li, Sittiporn Pattaradilokrat, Feng Zhu, Hongying Jiang, Shengfa Liu, Lingxian Hong, Yong Fu, Lily Koo, Wenyue Xu, Weiqing Pan, Jane M. Carlton, Osamu Kaneko, Richard Carter, John C. Wootton, Xin Zhuan Su

Research output: Contribution to journalArticlepeer-review

Abstract

Plasmodium yoelii is an excellent model for studying malaria pathogenesis that is often intractable to investigate using human parasites; however, genetic studies of the parasite have been hindered by lack of genome-wide linkage resources. Here, we performed 14 genetic crosses between three pairs of P. yoelii clones/subspecies, isolated 75 independent recombinant progeny from the crosses, and constructed a high-resolution linkage map for this parasite. Microsatellite genotypes from the progeny formed 14 linkage groups belonging to the 14 parasite chromosomes, allowing assignment of sequence contigs to chromosomes. Growth-related virulent phenotypes from 25 progeny of one of the crosses were significantly associated with a major locus on chromosome 13 and with two secondary loci on chromosomes 7 and 10. The chromosome 10 and 13 loci are both linked to day 5 parasitemia, and their effects on parasite growth rate are independent but additive. The locus on chromosome 7 is associated with day 10 parasitemia. The chromosome 13 locus spans ∼220 kb of DNA containing 51 predicted genes, including the P. yoelii erythrocyte binding ligand, in which a C741Y substitution in the R6 domain is implicated in the change of growth rate. Similarly, the chromosome 10 locus spans ∼234 kb with 71 candidate genes, containing a member of the 235-kDa rhoptry proteins (Py235) that can bind to the erythrocyte surface membrane. Atypical virulent phenotypes among the progeny were also observed. This study provides critical tools and information for genetic investigations of virulence and biology of P. yoelii.

Original languageEnglish (US)
Pages (from-to)E374-E382
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number31
DOIs
StatePublished - Aug 2 2011

Keywords

  • Crossover
  • Genetic mapping
  • Inheritance
  • Rodent

ASJC Scopus subject areas

  • General

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