The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
TLR4 polymorphisms, infectious diseases, and evolutionary pressure during migration of modern humans
Open accessAbstract
Infectious diseases exert a constant evolutionary pressure on the genetic makeup of our innate immune system. Polymorphisms in Toll-like receptor 4 ( TLR4 ) have been related to susceptibility to Gram-negative infections and septic shock. Here we show that two polymorphisms of TLR4 , Asp299Gly and Thr399Ile, have unique distributions in populations from Africa, Asia, and Europe. Genetic and functional studies are compatible with a model in which the nonsynonymous polymorphism Asp299Gly has evolved as a protective allele against malaria, explaining its high prevalence in subSaharan Africa. However, the same allele could have been disadvantageous after migration of modern humans into Eurasia, putatively because of increased susceptibility to severe bacterial infections. In contrast, the Asp299Gly allele, when present in cosegregation with Thr399Ile to form the Asp299Gly/Thr399Ile haplotype, shows selective neutrality. Polymorphisms in TLR4 exemplify how the interaction between our innate immune system and the infectious pressures in particular environments may have shaped the genetic variations and function of our immune system during the out-of-Africa migration of modern humans.
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Sepsis: pathophysiology and clinical management
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Metadata
- Authors
- Ferwerda, B., McCall, M. B. B., Alonso, S., Giamarellos-Bourboulis, E. J., Mouktaroudi, M., Izagirre, N., Syafruddin, D., Kibiki, G., Cristea, T., Hijmans, A., Hamann, L., Israel, S., ElGhazali, G., Troye-Blomberg, M., Kumpf, O., Maiga, B., Dolo, A., Doumbo, O., Hermsen, C. C., Stalenhoef, A. F. H., van Crevel, R., Brunner, H. G., Oh, D.-Y., Schumann, R. R., de la Rúa, C., Sauerwein, R., Kullberg, B.-J., van der Ven, A. J. A. M., van der Meer, J. W. M., & Netea, M. G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2007-10-16
- Volume
- 104
- Issue
- 42
- Pages
- 16645-16650
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2144136875
- Cited by
- 318
- References
- 4
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Open access
- green
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- Ferwerda, B., McCall, M. B. B., Alonso, S., Giamarellos-Bourboulis, E. J., Mouktaroudi, M., Izagirre, N., Syafruddin, D., Kibiki, G., Cristea, T., Hijmans, A., Hamann, L., Israel, S., ElGhazali, G., Troye-Blomberg, M., Kumpf, O., Maiga, B., Dolo, A., Doumbo, O., Hermsen, C. C., . . . Netea, M. G. (2007). TLR4 polymorphisms, infectious diseases, and evolutionary pressure during migration of modern humans. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0704828104
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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