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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
TLR4 polymorphisms, infectious diseases, and evolutionary pressure during migration of modern humans
Proceedings of the National Academy of Sciences of the United States of America, Volume 104, No. 42, Year 2007
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Description
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. © 2007 by The National Academy of Sciences of the USA.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2034238/bin/pnas_0704828104_index.html
Authors & Co-Authors
Ferwerda, Bart
Netherlands, Nijmegen
Radboud University Medical Center
McCall, Matthew B.B.
Netherlands, Nijmegen
Radboud University Medical Center
Alonso, Santos
Spain, Leioa
Universidad Del Pais Vasco
GIamarellos-Bourboulis, Evangelos J.
Greece, Athens
Attikon University Hospital
Mouktaroudi, Maria
Greece, Athens
Attikon University Hospital
Izagirre, Neskuts
Spain, Leioa
Universidad Del Pais Vasco
Syafruddin, D.
Indonesia, Jakarta
Eijkman Institute for Molecular Biology
Kibiki, Gibson S.
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Cristea, Tudor
Romania, Cluj Napoca
Universitatea de Medicina si Farmacie Iuliu Hatieganu Din Cluj-napoca
Hijmans, Anneke
Netherlands, Nijmegen
Radboud University Medical Center
Hamann, Lutz
Germany, Berlin
Charité – Universitätsmedizin Berlin
Israel, Shoshana
Israel, Jerusalem
Hadassah University Medical Centre
ElGhazali, Gehad Eltayeb B.
Sudan
Karthoum University
Troye-Blomberg, Marita
Sweden, Stockholm
Institutionen För Molekylär Biovetenskap, Wenner-grens Institut
Kumpf, Oliver
Germany, Berlin
Robert Rössle Klinik
Maïga, Boubacar B.
Mali, Bamako
University of Bamako
Dolo, Amagana I.
Mali, Bamako
University of Bamako
Doumbo, Ogobara K.
Mali, Bamako
University of Bamako
Hermsen, Cornelus C.R.
Netherlands, Nijmegen
Radboud University Medical Center
Stalenhóef, Anton F.H.
Netherlands, Nijmegen
Radboud University Medical Center
van Crevel, Reinout
Netherlands, Nijmegen
Radboud University Medical Center
Brunner, Han G.
Netherlands, Nijmegen
Radboud University Medical Center
Oh, Djin Ye
Germany, Berlin
Charité – Universitätsmedizin Berlin
Schumann, Ralf R.
Germany, Berlin
Charité – Universitätsmedizin Berlin
De La Rúa, Concepcion
Spain, Leioa
Universidad Del Pais Vasco
Sauerwein, Robert W.
Netherlands, Nijmegen
Radboud University Medical Center
Kullberg, Bart Jan
Netherlands, Nijmegen
Radboud University Medical Center
van der Ven, André J.A.M.
Netherlands, Nijmegen
Radboud University Medical Center
van der Meer, Jos W.M.D.
Netherlands, Nijmegen
Radboud University Medical Center
Netea, Mihai Gheorghe
Netherlands, Nijmegen
Radboud University Medical Center
Statistics
Citations: 321
Authors: 30
Affiliations: 12
Identifiers
Doi:
10.1073/pnas.0704828104
ISSN:
00278424
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study