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• W3082149023 abstract "Historically, chimpanzees were used for experimental genetic crosses between cloned Plasmodium falciparum parasites and have played a key role in determining genetic loci responsible for drug resistance, virulence, invasion, growth rate, and transmission. The human hepatocyte chimeric FRG huHep mouse has replaced the chimpanzee and allows for the routine generation of P. falciparum genetic crosses and the recovery of hundreds and potentially thousands of unique recombinant progeny, strengthening the power of genetic linkage mapping. Classical linkage mapping, bulk segregant analysis, CRISPR/Cas9 technology, and high-throughput ’omics techniques using recombinant progeny should allow for unprecedented power and efficiency to carry out a systems genetics approach to expand our understanding of P. falciparum biology. The first experimental crosses carried out with the human malaria parasite Plasmodium falciparum played a key role in determining the genetic loci responsible for drug resistance, virulence, invasion, growth rate, and transmission. These crosses relied on splenectomized chimpanzees to complete the liver stage of the parasite's life cycle and the subsequent transition to asexual blood stage culture followed by cloning of recombinant progeny in vitro. Crosses can now be routinely carried out using human-liver-chimeric mice infused with human erythrocytes to generate hundreds of unique recombinant progeny for genetic linkage mapping, bulk segregant analysis, and high-throughput ’omics readouts. The high number of recombinant progeny should allow for unprecedented power and efficiency in the execution of a systems genetics approach to study P. falciparum biology. The first experimental crosses carried out with the human malaria parasite Plasmodium falciparum played a key role in determining the genetic loci responsible for drug resistance, virulence, invasion, growth rate, and transmission. These crosses relied on splenectomized chimpanzees to complete the liver stage of the parasite's life cycle and the subsequent transition to asexual blood stage culture followed by cloning of recombinant progeny in vitro. Crosses can now be routinely carried out using human-liver-chimeric mice infused with human erythrocytes to generate hundreds of unique recombinant progeny for genetic linkage mapping, bulk segregant analysis, and high-throughput ’omics readouts. The high number of recombinant progeny should allow for unprecedented power and efficiency in the execution of a systems genetics approach to study P. falciparum biology. a linkage mapping approach that compares allele frequencies from different population pools segregated by phenotype. the contribution of a locus to the genetic variance of a given trait. an immunocompromised mouse, engrafted with human hepatocytes, that allows for P. falciparum liver stage development; with a transfusion of human erythrocytes it allows the transition of liver stage to blood stage. the genetic contribution to a phenotype. In the simplest case, a single major gene influences a phenotype. However, more typically, many genes influence a phenotype to varying degrees (each gene has a different effect size on the phenotype) and there are various interactions between these genes and the environment (genotype-by-genotype interactions and/or genotype-by-environment interactions). the broader whole genome context in which the phenotype of interest evolves and persists. The broader genetic context can include secondary (or modulatory) genes along with compensatory genes that play an important role in defining a phenotype. this approach uses a genome-wide set of genetic markers across a set of recombinant progeny and parents to determine if there are genetic loci associated with the phenotype of interest. Loci that are associated with the phenotype emerge as significant peaks in quantitative trait locus mapping. this approach analyzes genome-wide variation in a set of unrelated individuals to search for genotypic variants that are associated with a specific phenotype. a method in numerical ecology to estimate the species diversity in a community. the process by which a newly beneficial mutation arises and becomes fixed in the population. This includes hard selective sweeps (mutations in the chloroquine resistance transporter, PfCRT, conferring chloroquine resistance) and soft selective sweeps (multiple-point mutations in PfK13, conferring artemisinin resistance). a method using short oligonucleotide probes that preferentially bind to a target genome to amplify and sequence genomes of interest from contaminating host tissues. an approach to make sense of complex traits. It examines intermediate molecular phenotypes, such as transcript levels, protein and metabolite abundance, in an attempt to bridge the gap between DNA variation and the traits of interest. Of note, systems genetics methods can be integrated with GWAS to predict causal genes and their functions." @default.
• W3082149023 created "2020-09-08" @default.
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• W3082149023 date "2020-10-01" @default.
• W3082149023 modified "2023-10-02" @default.
• W3082149023 title "Humanized Mice and the Rebirth of Malaria Genetic Crosses" @default.
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• W3082149023 doi "https://doi.org/10.1016/j.pt.2020.07.009" @default.
• W3082149023 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7530086" @default.
• W3082149023 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32891493" @default.
• W3082149023 hasPublicationYear "2020" @default.
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