Haplotype structure and positive selection at TLR1 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-04

AUTHORS

Christopher Heffelfinger, Andrew J Pakstis, William C Speed, Allison P Clark, Eva Haigh, Rixun Fang, Mahohar R Furtado, Kenneth K Kidd, Michael P Snyder

ABSTRACT

Toll-like receptor 1, when dimerized with Toll-like receptor 2, is a cell surface receptor that, upon recognition of bacterial lipoproteins, activates the innate immune system. Variants in TLR1 associate with the risk of a variety of medical conditions and diseases, including sepsis, leprosy, tuberculosis, and others. The foremost of these is rs5743618 c.2079T>G(p.(Ile602Ser)), the derived allele of which is associated with reduced risk of sepsis, leprosy, and other diseases. Interestingly, 602Ser, which shows signatures of selection, inhibits TLR1 surface trafficking and subsequent activation of NFκB upon recognition of a ligand. This suggests that reduced TLR1 activity may be beneficial for human health. To better understand TLR1 variation and its link to human health, we have typed all 7 high-frequency missense variants (>5% in at least one population) along with 17 other variants in and around TLR1 in 2548 individuals from 56 populations from around the globe. We have also found additional signatures of selection on missense variants not associated with rs5743618, suggesting that there may be multiple functional alleles under positive selection in this gene. More... »

PAGES

551

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ejhg.2013.194

DOI

http://dx.doi.org/10.1038/ejhg.2013.194

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008991357

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24002163


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