TY - JOUR
KW - Toll-Like Receptor 1
KW - leprosy
AU - Heffelfinger C
AU - Pakstis A
AU - Speed W
AU - Clark AP
AU - Haigh E
AU - Fang R
AU - Furtado MR
AU - Kidd KK
AU - Snyder M
AB - 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.European Journal of Human Genetics advance online publication, 4 September 2013; doi:10.1038/ejhg.2013.194.
BT - European journal of human genetics : EJHG
C1 - http://www.ncbi.nlm.nih.gov/pubmed/24002163?dopt=Abstract
DA - 2013 Sep 4
DO - 10.1038/ejhg.2013.194
J2 - Eur. J. Hum. Genet.
LA - eng
N2 - 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.European Journal of Human Genetics advance online publication, 4 September 2013; doi:10.1038/ejhg.2013.194.
PY - 2013
T2 - European journal of human genetics : EJHG
TI - Haplotype structure and positive selection at TLR1.
SN - 1476-5438
ER -