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 journalArticle

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)
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number31
DOIs
StatePublished - Aug 2 2011

Fingerprint

Genetic Crosses
Plasmodium yoelii
Genetic Loci
Parasites
Chromosomes, Human, Pair 13
Chromosomes, Human, Pair 10
Phenotype
Growth
Chromosomes, Human, Pair 7
Parasitemia
Chromosomes, Human, Pair 14
Erythrocyte Membrane
Microsatellite Repeats
Genes
Malaria
Virulence
Clone Cells
Chromosomes
Erythrocytes
Genotype

Keywords

  • Crossover
  • Genetic mapping
  • Inheritance
  • Rodent

ASJC Scopus subject areas

  • General

Cite this

Linkage maps from multiple genetic crosses and loci linked to growth-related virulent phenotype in Plasmodium yoelii. / Li, Jian; Pattaradilokrat, Sittiporn; Zhu, Feng; Jiang, Hongying; Liu, Shengfa; Hong, Lingxian; Fu, Yong; Koo, Lily; Xu, Wenyue; Pan, Weiqing; Carlton, Jane M.; Kaneko, Osamu; Carter, Richard; Wootton, John C.; Su, Xin Zhuan.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 31, 02.08.2011.

Research output: Contribution to journalArticle

Li, J, Pattaradilokrat, S, Zhu, F, Jiang, H, Liu, S, Hong, L, Fu, Y, Koo, L, Xu, W, Pan, W, Carlton, JM, Kaneko, O, Carter, R, Wootton, JC & Su, XZ 2011, 'Linkage maps from multiple genetic crosses and loci linked to growth-related virulent phenotype in Plasmodium yoelii', Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 31. https://doi.org/10.1073/pnas.1102261108
Li, Jian ; Pattaradilokrat, Sittiporn ; Zhu, Feng ; Jiang, Hongying ; Liu, Shengfa ; Hong, Lingxian ; Fu, Yong ; Koo, Lily ; Xu, Wenyue ; Pan, Weiqing ; Carlton, Jane M. ; Kaneko, Osamu ; Carter, Richard ; Wootton, John C. ; Su, Xin Zhuan. / Linkage maps from multiple genetic crosses and loci linked to growth-related virulent phenotype in Plasmodium yoelii. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 31.
@article{85fbdb4c755941e9b524e1daf77f9cfa,
title = "Linkage maps from multiple genetic crosses and loci linked to growth-related virulent phenotype in Plasmodium yoelii",
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.",
keywords = "Crossover, Genetic mapping, Inheritance, Rodent",
author = "Jian Li and Sittiporn Pattaradilokrat and Feng Zhu and Hongying Jiang and Shengfa Liu and Lingxian Hong and Yong Fu and Lily Koo and Wenyue Xu and Weiqing Pan and Carlton, {Jane M.} and Osamu Kaneko and Richard Carter and Wootton, {John C.} and Su, {Xin Zhuan}",
year = "2011",
month = "8",
day = "2",
doi = "10.1073/pnas.1102261108",
language = "English (US)",
volume = "108",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "31",

}

TY - JOUR

T1 - Linkage maps from multiple genetic crosses and loci linked to growth-related virulent phenotype in Plasmodium yoelii

AU - Li, Jian

AU - Pattaradilokrat, Sittiporn

AU - Zhu, Feng

AU - Jiang, Hongying

AU - Liu, Shengfa

AU - Hong, Lingxian

AU - Fu, Yong

AU - Koo, Lily

AU - Xu, Wenyue

AU - Pan, Weiqing

AU - Carlton, Jane M.

AU - Kaneko, Osamu

AU - Carter, Richard

AU - Wootton, John C.

AU - Su, Xin Zhuan

PY - 2011/8/2

Y1 - 2011/8/2

N2 - 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.

AB - 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.

KW - Crossover

KW - Genetic mapping

KW - Inheritance

KW - Rodent

UR - http://www.scopus.com/inward/record.url?scp=79961213996&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79961213996&partnerID=8YFLogxK

U2 - 10.1073/pnas.1102261108

DO - 10.1073/pnas.1102261108

M3 - Article

VL - 108

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 31

ER -