Publication: The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice
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Issued Date
2021-12-01
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ISSN
23993642
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2-s2.0-85107968693
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Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Communications Biology. Vol.4, No.1 (2021)
Suggested Citation
Katrina A. Button-Simons, Sudhir Kumar, Nelly Carmago, Meseret T. Haile, Catherine Jett, Lisa A. Checkley, Spencer Y. Kennedy, Richard S. Pinapati, Douglas A. Shoue, Marina McDew-White, Xue Li, François H. Nosten, Stefan H. Kappe, Timothy J.C. Anderson, Jeanne Romero-Severson, Michael T. Ferdig, Scott J. Emrich, Ashley M. Vaughan, Ian H. Cheeseman The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice. Communications Biology. Vol.4, No.1 (2021). doi:10.1038/s42003-021-02210-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/75531
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Title
The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice
Author(s)
Katrina A. Button-Simons
Sudhir Kumar
Nelly Carmago
Meseret T. Haile
Catherine Jett
Lisa A. Checkley
Spencer Y. Kennedy
Richard S. Pinapati
Douglas A. Shoue
Marina McDew-White
Xue Li
François H. Nosten
Stefan H. Kappe
Timothy J.C. Anderson
Jeanne Romero-Severson
Michael T. Ferdig
Scott J. Emrich
Ashley M. Vaughan
Ian H. Cheeseman
Sudhir Kumar
Nelly Carmago
Meseret T. Haile
Catherine Jett
Lisa A. Checkley
Spencer Y. Kennedy
Richard S. Pinapati
Douglas A. Shoue
Marina McDew-White
Xue Li
François H. Nosten
Stefan H. Kappe
Timothy J.C. Anderson
Jeanne Romero-Severson
Michael T. Ferdig
Scott J. Emrich
Ashley M. Vaughan
Ian H. Cheeseman
Abstract
Genetic crosses are most powerful for linkage analysis when progeny numbers are high, parental alleles segregate evenly and numbers of inbred progeny are minimized. We previously developed a novel genetic crossing platform for the human malaria parasite Plasmodium falciparum, an obligately sexual, hermaphroditic protozoan, using mice carrying human hepatocytes (the human liver-chimeric FRG NOD huHep mouse) as the vertebrate host. We report on two genetic crosses—(1) an allopatric cross between a laboratory-adapted parasite (NF54) of African origin and a recently patient-derived Asian parasite, and (2) a sympatric cross between two recently patient-derived Asian parasites. We generated 144 unique recombinant clones from the two crosses, doubling the number of unique recombinant progeny generated in the previous 30 years. The allopatric African/Asian cross has minimal levels of inbreeding and extreme segregation distortion, while in the sympatric Asian cross, inbred progeny predominate and parental alleles segregate evenly. Using simulations, we demonstrate that these progeny provide the power to map small-effect mutations and epistatic interactions. The segregation distortion in the allopatric cross slightly erodes power to detect linkage in several genome regions. We greatly increase the power and the precision to map biomedically important traits with these new large progeny panels.