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Related Experiment Video

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qKAT: Quantitative Semi-automated Typing of Killer-cell Immunoglobulin-like Receptor Genes

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Published on: March 6, 2019

Haplotype structure and positive selection at TLR1.

Christopher Heffelfinger¹, Andrew J Pakstis², William C Speed²

¹1] Department of Genetics, Yale University, New Haven, CT, USA [2] Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA.

European Journal of Human Genetics : EJHG

|September 5, 2013

Summary

This summary is machine-generated.

Genetic variations in Toll-like receptor 1 (TLR1) impact innate immunity and disease risk. A specific variant (rs5743618) reduces sepsis risk by inhibiting TLR1 activity, suggesting evolutionary adaptation for health.

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Area of Science:

Immunology
Human Genetics
Evolutionary Biology

Background:

Toll-like receptor 1 (TLR1), partnered with TLR2, recognizes bacterial lipoproteins and activates innate immunity.
TLR1 variants are linked to diseases like sepsis, leprosy, and tuberculosis.
The rs5743618 variant (Ile602Ser) is associated with reduced disease risk and shows signs of positive selection.

Purpose of the Study:

To investigate the role of TLR1 variation in human health.
To identify functional TLR1 alleles under selection.

Main Methods:

Genotyping of 7 high-frequency missense variants and 17 other variants in and around TLR1.
Analysis of 2548 individuals from 56 global populations.
Examination of selection signatures on TLR1 variants.

Main Results:

The rs5743618 (Ile602Ser) variant inhibits TLR1 surface trafficking and NFκB activation, correlating with reduced sepsis risk.
Additional missense variants, independent of rs5743618, also exhibit signatures of positive selection.
Multiple functional TLR1 alleles may be under positive selection across diverse populations.

Conclusions:

Reduced TLR1 activity, as seen with the 602Ser variant, appears beneficial for human health.
Evidence suggests ongoing positive selection on multiple TLR1 variants, indicating adaptation to pathogen pressures.
Further research into TLR1 variation can illuminate its complex role in immunity and disease susceptibility.