EGAGenomicsIllumina HumanOmni5-Quad and exome sequencinghttps://ega-archive.org/datasets/EGAD00010001131200EGA dataset EGAD00010001131EGAHumans differ in the outcome that follows exposure to life-threatening pathogens, yet the extent of population differences in immune responses and their genetic and evolutionary determinants remain undefined. Here, we characterized, using RNA sequencing, the transcriptional response of primary monocytes from Africans and Europeans to bacterial and viral stimuli-ligands activating Toll-like receptor pathways (TLR1/2, TLR4, and TLR7/8) and influenza virus-and mapped expression quantitative trait loci (eQTLs). We identify numerous cis-eQTLs that contribute to the marked differences in immune responses detected within and between populations and a strong trans-eQTL hotspot at TLR1 that decreases expression of pro-inflammatory genes in Europeans only. We find that immune-responsive regulatory variants are enriched in population-specific signals of natural selection and show that admixture with Neandertals introduced regulatory variants into European genomes, affecting preferentially responses to viral challenges. Together, our study uncovers evolutionarily important determinants of differences in host immune responsiveness between human populations.Genetic Adaptation and Neandertal Admixture Shaped the Immune System of Human Populations.Quach Hélène H, Rotival Maxime M, Pothlichet Julien J, Loh Yong-Hwee Eddie YE, Dannemann Michael M, Zidane Nora N, Laval Guillaume G, Patin Etienne E, Harmant Christine C, Lopez Marie M, Deschamps Matthieu M, Naffakh Nadia N, Duffy Darragh D, Coen Anja A, Leroux-Roels Geert G, Clément Frederic F, Boland Anne A, Deleuze Jean-François JF, Kelso Janet J, Albert Matthew L ML, Quintana-Murci Lluis LWES, Complete Transcriptome, Complete, Complete Transcriptome Sequencing, Exome Sequencings, Occidental, wide/broad, Complete Exome Sequencings, Genomes, Complete Exome, Complete Exome Sequencing, Whole Transcriptome Sequencing, Exome, white, whole genome, broad, Sequencing, wide, Exome Sequencing, Whole Exome, Caucasian, Whites, European, Whole, Whole Exome Sequencing, White, Whole Transcriptome, Transcriptome Sequencing, African unspecified., Transcriptome Sequencings, Caucasoid, Caucasiansbig, whole exome, Complete Exome, stRNA, SCF receptor activity, Mini Exon, Xkl-1, composed of, brl, HiSeq 2000, Small, large, KL receptor activity, DmelCG4114, Gsfsco1, Caucasian, scfr, Regions, Mini-Exon, SCO5, Whole Transcriptome, Transcriptome Sequencing, SCO1, Gsfsow3, SCFR, Gsfsco5, SOW3, WES, Fdc, Complete, Small Temporal, Occidental, Exome Sequencings, Complete Exome Sequencing, Whole Transcriptome Sequencing, composition, W, miRNA, Primary miRNA, pri-miRNA, Sequencing, Whole Exome, UTRs, Whole, great, Bs, African unspecified, Sl, whole exome., pre miRNA, HHT1, proto-oncogene c-Kit, RNA, Complete Exome Sequencings, Edg, Exome, CG4114, Small Temporal RNA, white, Tr-kit, Primary, compositionality, Expanded, PBT, Exome Sequencing, Micro RNA, KIT ligand receptor activity, European, 1270, kl1-A, KIT, Region, pre-miRNA, END, Caucasoid, XKrk1, Caucasians, Untranslated Region, pri miRNA, tyrosine-protein kinase Kit, pbt, Complete Transcriptome, c-KIT, miRNAs, Complete Transcriptome Sequencing, Micro, Temporal RNA, Mini-Exons, content, expanded, Exomes, Untranslated, Ex, Exon, Primary MicroRNA, kit, CD117, l(2)01270, c-kit, enlarged, C-Kit, Whites, Ssm, structure, Whole Exome Sequencing, xkl-1, l(2)ey, White, MicroRNA, ORW1, Transcriptome Sequencings, krk1genetic, Human, Immune, human being, Immune Systems, Man (Taxonomy), Homo sapiens, Modern Man, System, Systems, Modern, familial, inherited genetic, constitutitional genetic, hereditary, human., Manextent, Influenza in Human, influenza infection, host organism, lifespan, Influenza with other manifestations, Materials, human being, RNA Sequence Determination, Influenza with other manifestations NOS (disorder), Sequence Determination, RNA Sequence, Receptors, Gene, Trait Loci, 2610511A05Rik, Quantitative, TOLL, Human, BB234005, School-Age, Caucasian, Homo sapiens, resilient, responsivity, tough, Core Genome, fam:TLR, Virus, Genetic Selection, ARMD10, Analysis, Toll Like, Animal, Man, School-Age Populations, reactivity, strong, study, Toll Like Receptor, Animal Virus, Selection, Occidental, Man (Taxonomy), Ly87, Genetic, Viruses, Analyses, Genomes, Determination, entire lifespan, Natural, entire life cycle, Lps, Flu, Accessory Genome, TLR7-like, Trait Locus, Population, Natural Selection, Sequence Determinations, Sequencing, Toll Like Receptors, genetic, CD284, Monocyte, RNA Sequence Analyses, Loci, flu, Human Flu, Influenza in Humans, Protein G18, RNA Sequencing, Influenza, Influenza with non-respiratory manifestation (disorder), School Age Population, Quantitative Trait Loci Genes, Grippe, constitutitional genetic, Influenza with other manifestations (disorder), BACTS2, orthomyxoviridae disease or disorder, Sequence Analyses, Influenzas, ahl4, RNA, Ligand, completeness, RNA Sequence Determinations, Modern, familial, white, Toll-Like Receptor, influenza with non-respiratory manifestation, Cistrons, Pangenome, Determinations, Quantitative Trait, School Age, Cis, CIS, European, orthomyxoviridae caused disease or disorder, Quantitative Trait Locus, G18, Genetic Materials, Zoophaginae, human., Genetic Material, Caucasoid, Rasl2-8, Caucasians, influenza, TLR-4, Populations, CIS-1, Toll-Like, Human Influenza, life, influenza virus infection, 9030605P22Rik, Ran|M1, School Age Populations, Locus, orthomyxoviridae infectious disease, Ran/M1, Human Influenzas, Pan-genome, SOCS, Material, Whites, Modern Man, RNA Sequence Analysis, Animal Viruses, Cistron, White, inherited genetic, School-Age Population, Receptor, response, responsive, Suppressor of cytokine signaling, hereditary, humansfalseGenome-wide genotyping data and exome sequencing of 100 European-descent and 100 African-descent Belgians used in the EGAS000010The 100 European-descent (EUB) and 100 African-descent (AFB) Belgians studied were genotyped for a total of 4,301,332 SNPs on the Illumina HumanOmni5-Quad BeadChips. Whole-exome sequencing was carried out for the same 200 individuals with the Nextera Rapid Capture Expanded Exome kit, on the Illumina HiSeq 2000 platform, with 100-bp paired-end reads. This kit delivers 62 Mb of genomic content per individual, including exons, untranslated regions (UTR), and microRNAs. Omni5 and exome datasets were merged, yielding a concordance rate between platforms of 99.93%.2017-07-26 15:39:28EGAD00010001131960627768888EGAC00001000139EGAS00001001895