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The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice
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, h...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203791/ https://www.ncbi.nlm.nih.gov/pubmed/34127785 http://dx.doi.org/10.1038/s42003-021-02210-1 |
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author | Button-Simons, Katrina A. Kumar, Sudhir Carmago, Nelly Haile, Meseret T. Jett, Catherine Checkley, Lisa A. Kennedy, Spencer Y. Pinapati, Richard S. Shoue, Douglas A. McDew-White, Marina Li, Xue Nosten, François H. Kappe, Stefan H. Anderson, Timothy J. C. Romero-Severson, Jeanne Ferdig, Michael T. Emrich, Scott J. Vaughan, Ashley M. Cheeseman, Ian H. |
author_facet | Button-Simons, Katrina A. Kumar, Sudhir Carmago, Nelly Haile, Meseret T. Jett, Catherine Checkley, Lisa A. Kennedy, Spencer Y. Pinapati, Richard S. Shoue, Douglas A. McDew-White, Marina Li, Xue Nosten, François H. Kappe, Stefan H. Anderson, Timothy J. C. Romero-Severson, Jeanne Ferdig, Michael T. Emrich, Scott J. Vaughan, Ashley M. Cheeseman, Ian H. |
author_sort | Button-Simons, Katrina A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8203791 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-82037912021-07-01 The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice Button-Simons, Katrina A. Kumar, Sudhir Carmago, Nelly Haile, Meseret T. Jett, Catherine Checkley, Lisa A. Kennedy, Spencer Y. Pinapati, Richard S. Shoue, Douglas A. McDew-White, Marina Li, Xue Nosten, François H. Kappe, Stefan H. Anderson, Timothy J. C. Romero-Severson, Jeanne Ferdig, Michael T. Emrich, Scott J. Vaughan, Ashley M. Cheeseman, Ian H. Commun Biol Article 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. Nature Publishing Group UK 2021-06-14 /pmc/articles/PMC8203791/ /pubmed/34127785 http://dx.doi.org/10.1038/s42003-021-02210-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Button-Simons, Katrina A. Kumar, Sudhir Carmago, Nelly Haile, Meseret T. Jett, Catherine Checkley, Lisa A. Kennedy, Spencer Y. Pinapati, Richard S. Shoue, Douglas A. McDew-White, Marina Li, Xue Nosten, François H. Kappe, Stefan H. Anderson, Timothy J. C. Romero-Severson, Jeanne Ferdig, Michael T. Emrich, Scott J. Vaughan, Ashley M. Cheeseman, Ian H. The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice |
title | The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice |
title_full | The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice |
title_fullStr | The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice |
title_full_unstemmed | The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice |
title_short | The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice |
title_sort | power and promise of genetic mapping from plasmodium falciparum crosses utilizing human liver-chimeric mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203791/ https://www.ncbi.nlm.nih.gov/pubmed/34127785 http://dx.doi.org/10.1038/s42003-021-02210-1 |
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