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Deciphering the genetic control of gene expression following Mycobacterium leprae antigen stimulation
Leprosy is a human infectious disease caused by Mycobacterium leprae. A strong host genetic contribution to leprosy susceptibility is well established. However, the modulation of the transcriptional response to infection and the mechanism(s) of disease control are poorly understood. To address this...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5565194/ https://www.ncbi.nlm.nih.gov/pubmed/28793313 http://dx.doi.org/10.1371/journal.pgen.1006952 |
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author | Manry, Jérémy Nédélec, Yohann Fava, Vinicius M. Cobat, Aurélie Orlova, Marianna Thuc, Nguyen Van Thai, Vu Hong Laval, Guillaume Barreiro, Luis B. Schurr, Erwin |
author_facet | Manry, Jérémy Nédélec, Yohann Fava, Vinicius M. Cobat, Aurélie Orlova, Marianna Thuc, Nguyen Van Thai, Vu Hong Laval, Guillaume Barreiro, Luis B. Schurr, Erwin |
author_sort | Manry, Jérémy |
collection | PubMed |
description | Leprosy is a human infectious disease caused by Mycobacterium leprae. A strong host genetic contribution to leprosy susceptibility is well established. However, the modulation of the transcriptional response to infection and the mechanism(s) of disease control are poorly understood. To address this gap in knowledge of leprosy pathogenicity, we conducted a genome-wide search for expression quantitative trait loci (eQTL) that are associated with transcript variation before and after stimulation with M. leprae sonicate in whole blood cells. We show that M. leprae antigen stimulation mainly triggered the upregulation of immune related genes and that a substantial proportion of the differential gene expression is genetically controlled. Indeed, using stringent criteria, we identified 318 genes displaying cis-eQTL at an FDR of 0.01, including 66 genes displaying response-eQTL (reQTL), i.e. cis-eQTL that showed significant evidence for interaction with the M. leprae stimulus. Such reQTL correspond to regulatory variations that affect the interaction between human whole blood cells and M. leprae sonicate and, thus, likely between the human host and M. leprae bacilli. We found that reQTL were significantly enriched among binding sites of transcription factors that are activated in response to infection, and that they were enriched among single nucleotide polymorphisms (SNPs) associated with susceptibility to leprosy per se and Type-I Reaction, and seven of them have been targeted by recent positive selection. Our study suggested that natural selection shaped our genomic diversity to face pathogen exposure including M. leprae infection. |
format | Online Article Text |
id | pubmed-5565194 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55651942017-08-25 Deciphering the genetic control of gene expression following Mycobacterium leprae antigen stimulation Manry, Jérémy Nédélec, Yohann Fava, Vinicius M. Cobat, Aurélie Orlova, Marianna Thuc, Nguyen Van Thai, Vu Hong Laval, Guillaume Barreiro, Luis B. Schurr, Erwin PLoS Genet Research Article Leprosy is a human infectious disease caused by Mycobacterium leprae. A strong host genetic contribution to leprosy susceptibility is well established. However, the modulation of the transcriptional response to infection and the mechanism(s) of disease control are poorly understood. To address this gap in knowledge of leprosy pathogenicity, we conducted a genome-wide search for expression quantitative trait loci (eQTL) that are associated with transcript variation before and after stimulation with M. leprae sonicate in whole blood cells. We show that M. leprae antigen stimulation mainly triggered the upregulation of immune related genes and that a substantial proportion of the differential gene expression is genetically controlled. Indeed, using stringent criteria, we identified 318 genes displaying cis-eQTL at an FDR of 0.01, including 66 genes displaying response-eQTL (reQTL), i.e. cis-eQTL that showed significant evidence for interaction with the M. leprae stimulus. Such reQTL correspond to regulatory variations that affect the interaction between human whole blood cells and M. leprae sonicate and, thus, likely between the human host and M. leprae bacilli. We found that reQTL were significantly enriched among binding sites of transcription factors that are activated in response to infection, and that they were enriched among single nucleotide polymorphisms (SNPs) associated with susceptibility to leprosy per se and Type-I Reaction, and seven of them have been targeted by recent positive selection. Our study suggested that natural selection shaped our genomic diversity to face pathogen exposure including M. leprae infection. Public Library of Science 2017-08-09 /pmc/articles/PMC5565194/ /pubmed/28793313 http://dx.doi.org/10.1371/journal.pgen.1006952 Text en © 2017 Manry et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Manry, Jérémy Nédélec, Yohann Fava, Vinicius M. Cobat, Aurélie Orlova, Marianna Thuc, Nguyen Van Thai, Vu Hong Laval, Guillaume Barreiro, Luis B. Schurr, Erwin Deciphering the genetic control of gene expression following Mycobacterium leprae antigen stimulation |
title | Deciphering the genetic control of gene expression following Mycobacterium leprae antigen stimulation |
title_full | Deciphering the genetic control of gene expression following Mycobacterium leprae antigen stimulation |
title_fullStr | Deciphering the genetic control of gene expression following Mycobacterium leprae antigen stimulation |
title_full_unstemmed | Deciphering the genetic control of gene expression following Mycobacterium leprae antigen stimulation |
title_short | Deciphering the genetic control of gene expression following Mycobacterium leprae antigen stimulation |
title_sort | deciphering the genetic control of gene expression following mycobacterium leprae antigen stimulation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5565194/ https://www.ncbi.nlm.nih.gov/pubmed/28793313 http://dx.doi.org/10.1371/journal.pgen.1006952 |
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