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Cited by 47Genetic Associations and EpidemiologyPleistocene-Era Hominins and ArchaeologyEvolution and Genetic Dynamics

Detection of Neanderthal Adaptively Introgressed Genetic Variants That Modulate Reporter Gene Expression in Human Immune Cells

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Jagoda, Evelyn, Xue, James R, Reilly, Steven K, Dannemann, Michael, Racimo, Fernando, Huerta-Sanchez, Emilia, Sankararaman, Sriram, Kelso, Janet +3 more·2022·Molecular Biology and Evolution
DOI 10.1093/molbev/msab304PMC PMC8760939
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Abstract

Although some variation introgressed from Neanderthals has undergone selective sweeps, little is known about its functional significance. We used a Massively Parallel Reporter Assay (MPRA) to assay 5,353 high-frequency introgressed variants for their ability to modulate the gene expression within 170 bp of endogenous sequence. We identified 2,548 variants in active putative cis-regulatory elements (CREs) and 292 expression-modulating variants (emVars). These emVars are predicted to alter the binding motifs of important immune transcription factors, are enriched for associations with neutrophil and white blood cell count, and are associated with the expression of genes that function in innate immune pathways including inflammatory response and antiviral defense. We combined the MPRA data with other data sets to identify strong candidates to be driver variants of positive selection including an emVar that may contribute to protection against severe COVID-19 response. We endogenously deleted two CREs containing expression-modulation variants linked to immune function, rs11624425 and rs80317430, identifying their primary genic targets as ELMSAN1, and PAN2 and STAT2, respectively, three genes differentially expressed during influenza infection. Overall, we present the first database of experimentally identified expression-modulating Neanderthal-introgressed alleles contributing to potential immune response in modern humans.

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  • Jagoda et al. has shown large impact on gene expression associated with the presence of Neanderthal aSNPs in vitro.

    “Similarly, Jagoda et al. has shown large impact on gene expression associated with the presence of Neanderthal aSNPs in vitro [73].”

    From Denisovan introgression has shaped the immune system of present-day Papuans (2022) · cites this paper as [73]

    The Results section, “292 Introgressed Variants Modulated Reporter Gene Expression” (page unavailable), reports that 292 Neanderthal-introgressed variants significantly changed reporter expression in K562 cells, supporting an in vitro effect. But those variants were 5.5% of the variants tested, and the passage establishes statistical significance rather than a generally “large impact” on gene expression. (LLM, conf=0.84)

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Research works printed but not linked: 71

  1. 1000 Genomes Project Consortium. 2015. A global reference for human genetic variation. Nature 526: 68– 74. 26432245 PMC4750478
  2. Astle WJ, Elding H, Jiang T, Allen D, Ruklisa D, Mann AL, Mead D, Bouman H, Riveros-Mckay F, Kostadima MA, et al 2016. The allelic landscape of human blood cell trait variation and links to common complex disease. Cell 167(5): 1415– 1429. 27863252 PMC5300907
  3. Bath P, Algert C, Chapman N, Neal B, PROGRESS Collaborative Group. 2004. Association of mean platelet volume with risk of stroke among 3134 individuals with history of cerebrovascular disease. Stroke 35(3): 622– 626. 14976328
  4. Benson G. 1999. Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Res. 27(2): 573– 580. 9862982 PMC148217
  5. Bett JS, Ibrahim AFM, Garg AK, Kelly V, Pedrioli P, Rocha S, Hay RT. 2013. The P-body component USP52/PAN2 is a novel regulator of HIF1A mRNA stability. Biochem J. 451(2): 185– 194. 23398456 PMC3632086
  6. Boudewijns R, Thibaut HJ, Kaptein SJF, Li R, Vergote V, Seldeslachts L, Van Weyenbergh J, De Keyzer C, Bervoets L, Sharma S, et al 2020. STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters. Nat Commun. 11(1): 5838. 33203860 PMC7672082
  7. Butler MO, Hirano N. 2014. Human cell-based artificial antigen-presenting cells for cancer immunotherapy. Immunol Rev. 257(1): 191– 209. 24329798 PMC3869003
  8. COVID-19 Host Genetics Initiative. 2020. The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic. Eur J Hum Genet. 28: 715– 718. 32404885 PMC7220587
  9. Dannemann M. 2021. The population-specific impact of Neandertal introgression on human disease. Genome Biol Evol. 13(1): evaa250. 33247712 PMC7851588
  10. Deng Y-J, Ren E-H, Yuan W-H, Zhang G-Z, Wu Z-L, Xie Q-Q. 2020. GRB10 and E2F3 as diagnostic markers of osteoarthritis and their correlation with immune infiltration. Diagnostics (Basel) 10(3): 171. PMC7151213 32235747
  11. Deschamps M, Laval G, Fagny M, Itan Y, Abel L, Casanova J-L, Patin E, Quintana-Murci L. 2016. Genomic signatures of selective pressures and introgression from archaic hominins at human innate immunity genes. Am J Hum Genet. 98(1): 5– 21. 26748513 PMC4716683
  12. Dideberg V, Kristjansdottir G, Milani L, Libioulle C, Sigurdsson S, Louis E, Wiman A-C, Vermeire S, Rutgeerts P, Belaiche J, et al An. 2007. Insertion–deletion polymorphism in the interferon regulatory factor 5 (IRF5) gene confers risk of inflammatory bowel diseases. Hum Mol Genet. 16(24): 3008– 3016. 17881657
  13. Dinarello CA, Novick D, Kim S, Kaplanski G. 2013. Interleukin-18 and IL-18 binding protein. Front Immunol. 4: 289. 24115947 PMC3792554
  14. Dupuis-Maurin V, Brinza L, Baguet J, Plantamura E, Schicklin S, Chambion S, Macari C, Tomkowiak M, Deniaud E, Leverrier Y, et al 2015. Overexpression of the transcription factor Sp1 activates the OAS-RNAse L-RIG-I pathway. PLoS One 10(3): e0118551. 25738304 PMC4349862
  15. Enard D, Petrov DA. 2018. Evidence that RNA viruses drove adaptive introgression between Neanderthals and modern humans. Cell 175(2): 360– 371. 30290142 PMC6176737
  16. Encode Project Consortium. 2012. An integrated encyclopedia of DNA elements in the human genome. Nature 489(7414): 57– 74. 22955616 PMC3439153
  17. Ernst J, Kellis M. 2017. Chromatin-state discovery and genome annotation with ChromHMM. Nat Protoc. 12(12): 2478– 2492. 29120462 PMC5945550
  18. Fang J, Ding Z. 2020. SNAI1 is a prognostic biomarker and correlated with immune infiltrates in gastrointestinal cancers. Aging (Albany NY). 12(17): 17167– 17208. 32833672 PMC7521489
  19. Gittelman RM, Schraiber JG, Vernot B, Mikacenic C, Wurfel MM, Akey JM. 2016. Archaic hominin admixture facilitated adaptation to out-of-Africa environments. Curr Biol. 26(24): 3375– 3382. 27839976 PMC6764441
  20. Grant CE, Bailey TL, Noble WS. 2011. FIMO: scanning for occurrences of a given motif. Bioinformatics 2727(7): 1017– 1018. PMC3065696 21330290
  21. GTEx Consortium. 2015. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science 348: 648– 660. 25954001 PMC4547484
  22. Huang DW, Sherman BT, Lempicki RA. 2009a. Systematic and integrative analysis of large gene lists using DAVID Bioinformatics Resources. Nat Protoc. 4(1): 44– 57. 19131956
  23. Huang DW, Sherman BT, Lempicki RA. 2009b. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37(1): 1– 13. 19033363 PMC2615629
  24. Huerta-Sánchez E, Jin X, Asan Bianba Z, Peter BM, Vinckenbosch N, Liang Y, Yi X, He M, Somel M, Ni P, et al 2014. Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA. Nature 512: 194– 197. 25043035 PMC4134395
  25. Hunt SE, McLaren W, Gil L, Thormann A, Schuilenburg H, Sheppard D, Parton A, Armean IM, Trevanion SJ, Flicek P, et al 2018. Ensembl variation resources. Database 2018:bay119. PMC6310513 30576484
  26. Inoue F, Kircher M, Martin B, Cooper GM, Witten DM, McManus MT, Ahituv N, Shendure J. 2017. A systematic comparison reveals substantial differences in chromosomal versus episomal encoding of enhancer activity. Genome Res. 27(1): 38– 52. 27831498 PMC5204343
  27. Ip YT, Kraut R, Levine M, Rushlow CA. 1991. The dorsal morphogen is a sequence-specific DNA-binding protein that interacts with a long-range repression element in Drosophila. Cell 64(2): 439– 446. 1988156
  28. Jagoda E, Lawson DJ, Wall JD, Lambert D, Muller C, Westaway M, Leavesley M, Capellini TD, Mirazón Lahr M, Gerbault P, et al 2018. Disentangling immediate adaptive introgression from selection on standing introgressed variation in humans. Mol Biol Evol. 35(3): 623– 630. 29220488 PMC5850494
  29. Jassal B, Matthews L, Viteri G, Gong C, Lorente P, Fabregat A, Sidiropoulos K, Cook J, Gillespie M, Haw R, et al 2020. The reactome pathway knowledgebase. Nucleic Acids Res. 48(D1): D498– D503. 31691815 PMC7145712
  30. Kulakovskiy IV, Vorontsov IE, Yevshin IS, Sharipov RN, Fedorova AD, Rumynskiy EI, Medvedeva YA, Magana-Mora A, Bajic VB, Papatsenko DA, et al 2017. HOCOMOCO: towards a complete collection of transcription factor binding models for human and mouse via large-scale ChIP-Seq analysis. Nucleic Acids Res. 46(D1):D252–D259. PMC5753240 29140464
  31. Love MI, Huber W, Anders S. 2014. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15(12): 550. 25516281 PMC4302049
  32. Mendez FL, Watkins JC, Hammer MF. 2012. A haplotype at STAT2 introgressed from neanderthals and serves as a candidate of positive selection in Papua New Guinea. Am J Hum Genet. 91(2): 265– 274. 22883142 PMC3415544
  33. Mizuno A, Okada Y. 2019. Biological characterization of expression quantitative trait loci (eQTLs) showing tissue-specific opposite directional effects. Eur J Hum Genet. 27(11): 1745– 1756. 31296926 PMC6871526
  34. Nei Y, Obata-Ninomiya K, Tsutsui H, Ishiwata K, Miyasaka M, Matsumoto K, Nakae S, Kanuka H, Inase N, Karasuyama H, et al 2013. GATA-1 regulates the generation and function of basophils. Proc Natl Acad Sci U S A. 110(46): 18620– 18625. 24167252 PMC3831963
  35. Nielsen R, Hellmann I, Hubisz M, Bustamante C, Clark AG. 2007. Recent and ongoing selection in the human genome. Nat Rev Genet. 8(11): 857– 868. 17943193 PMC2933187
  36. Pagani L, Lawson DJ, Jagoda E, Mörseburg A, Eriksson A, Mitt M, Clemente F, Hudjashov G, DeGiorgio M, Saag L, et al 2016. Genomic analyses inform on migration events during the peopling of Eurasia. Nature 538(7624): 238– 242. 27654910 PMC5164938
  37. Palazon A, Goldrath AW, Nizet V, Johnson RS. 2014. HIF transcription factors, inflammation, and immunity. Immunity 41(4): 518– 528. 25367569 PMC4346319
  38. Pan F, Ye Z, Cheng L, Liu JO. 2004. Myocyte enhancer factor 2 mediates calcium-dependent transcription of the interleukin-2 gene in T lymphocytes: a calcium signaling module that is distinct from but collaborates with the nuclear factor of activated T cells (NFAT). J Biol Chem. 279(15): 14477– 14480. 14722108
  39. Pastore N, Brady OA, Diab HI, Martina JA, Sun L, Huynh T, Lim J-A, Zare H, Raben N, Ballabio A. 2016. TFEB and TFE3 cooperate in the regulation of the innate immune response in activated macrophages. Autophagy 12(8): 1240– 1258. 27171064 PMC4968228
  40. Pers TH, Timshel P, Hirschhorn JN. 2015. SNPsnap: a Web-based tool for identification and annotation of matched SNPs. Bioinformatics 31(3): 418– 420. 25316677 PMC4308663
  41. Petr M, Pääbo S, Kelso J, Vernot B. 2019. Limits of long-term selection against Neandertal introgression. Proc Natl Acad Sci U S A. 116(5): 1639– 1644. 30647110 PMC6358679
  42. Prüfer K, de Filippo C, Grote S, Mafessoni F, Korlević P, Hajdinjak M, Vernot B, Skov L, Hsieh P, Peyrégne S, et al 2017. A high-coverage Neandertal genome from Vindija Cave in Croatia. Science 358(6363): 655– 658. 28982794 PMC6185897
  43. Prüfer K, Racimo F, Patterson N, Jay F, Sankararaman S, Sawyer S, Heinze A, Renaud G, Sudmant PH, de Filippo C, et al 2014. The complete genome sequence of a Neanderthal from the Altai Mountains. Nature 505(7481): 43– 49. 24352235 PMC4031459
  44. Quach H, Rotival M, Pothlichet J, Loh Y-HE, Dannemann M, Zidane N, Laval G, Patin E, Harmant C, Lopez M, et al 2016. Genetic adaptation and Neandertal admixture shaped the immune system of human populations. Cell 167(3): 643– 656.e17. 27768888 PMC5075285
  45. Racimo F, Marnetto D, Huerta-sánchez E. 2017. Signatures of archaic adaptive introgression in present-day. Mol Biol Evol. 34(2): 296– 317. 27756828 PMC5400396
  46. Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. 2013. Genome engineering using the CRISPR-Cas9 system. Nat Protoc. 8(11): 2281– 2308. 24157548 PMC3969860
  47. Rueda B, Reddy MVPL, González-Gay MA, Balsa A, Pascual-Salcedo D, Petersson IF, Eimon A, Paira S, Scherbarth HR, Pons-Estel BA, et al 2006. Analysis of IRF5 gene functional polymorphisms in rheumatoid arthritis. Arthritis Rheum. 54(12): 3815– 3819. 17133578
  48. Sams AJ, Dumaine A, Nédélec Y, Yotova V, Alfieri C, Tanner JE, Messer PW, Barreiro LB. 2016. Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans. Genome Biol. 17(1): 1– 15. 27899133 PMC5129249
  49. Sankararaman S, Mallick S, Patterson N, Reich D. 2016. The combined landscape of Denisovan and Neanderthal ancestry in present-day humans. Curr Biol. 26(9): 1241– 1247. 27032491 PMC4864120
  50. Settembre C, Di Malta C, Polito VA, Garcia Arencibia M, Vetrini F, Erdin S, Erdin SU, Huynh T, Medina D, Colella P, et al 2011. TFEB links autophagy to lysosomal biogenesis. Science 332(6036): 1429– 1433. 21617040 PMC3638014
  51. Shapira SD, Gat-Viks I, Shum BOV, Dricot A, de Grace MM, Wu L, Gupta PB, Hao T, Silver SJ, Root DE, et al 2009. A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection. Cell 139(7): 1255– 1267. 20064372 PMC2892837
  52. Simonti CN, Vernot B, Bastarache L, Bottinger E, Carrell DS, Chisholm RL, Crosslin DR, Hebbring SJ, Jarvik GP, Kullo IJ, et al 2016. The phenotypic legacy of admixture between modern humans and Neandertals. Science 351(6274): 737– 741. 26912863 PMC4849557
  53. Sivan G, Martin SE, Myers TG, Buehler E, Szymczyk KH, Ormanoglu P, Moss B. 2013. Human genome-wide RNAi screen reveals a role for nuclear pore proteins in poxvirus morphogenesis. Proc Natl Acad Sci U S A. 110(9): 3519– 3524. 23401514 PMC3587217
  54. Sloan CA, Chan ET, Davidson JM, Malladi VS, Strattan JS, Hitz BC, Gabdank I, Narayanan AK, Ho M, Lee BT, et al 2016. ENCODE data at the ENCODE portal. Nucleic Acids Res. 44(D1): D726– D732. 26527727 PMC4702836
  55. Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, Downey P, Elliott P, Green J, Landray M, et al 2015. UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 12(3): e1001779. 25826379 PMC4380465
  56. Suliman HB, Sweeney TE, Withers CM, Piantadosi CA. 2010. Co-regulation of nuclear respiratory factor-1 by NFkappaB and CREB links LPS-induced inflammation to mitochondrial biogenesis. J Cell Sci. 123(Pt 15): 2565– 2575. 20587593 PMC2912462
  57. Tabilio A, Pelicci PG, Vinci G, Mannoni P, Civin CI, Vainchenker W, Testa U, Lipinski M, Rochant H, Breton-Gorius J, et al 1983. Myeloid and megakaryocytic properties of K-562 cell lines. Cancer Res. 43(10): 4569– 4574. 6349795
  58. Trikha P, Sharma N, Pena C, Reyes A, Pécot T, Khurshid S, Rawahneh M, Moffitt J, Stephens JA, Fernandez SA, et al 2016. E2f3 in tumor macrophages promotes lung metastasis. Oncogene 35(28): 3636– 3646. 26549026 PMC4861698
  59. Trimarchi JM, Fairchild B, Verona R, Moberg K, Andon N, Lees JA. 1998. E2F-6, a member of the E2F family that can behave as a transcriptional repressor. Proc Natl Acad Sci U S A. 95(6): 2850– 2855. 9501179 PMC19658
  60. Uebbing S, Gockley J, Reilly SK, Kocher AA, Geller E, Gandotra N, Scharfe C, Cotney J, Noonan JP. 2021. Massively parallel discovery of human-specific substitutions that alter enhancer activity. Proc Natl Acad Sci U S A. 118(2): e2007049118. 33372131 PMC7812811
  61. Ulirsch JC, Nandakumar SK, Wang L, Giani FC, Zhang X, Rogov P, Melnikov A, McDonel P, Do R, Mikkelsen TS, et al 2016. Systematic functional dissection of common genetic variation affecting red blood cell traits. Cell 165(6): 1530– 1545. 27259154 PMC4893171
  62. Vernot B, Tucci S, Kelso J, Schraiber JG, Wolf AB, Gittelman RM, Dannemann M, Grote S, McCoy RC, Norton H, et al 2016. Excavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals. Science 352(6282): 235– 239. 26989198 PMC6743480
  63. Visvikis O, Ihuegbu N, Labed SA, Luhachack LG, Alves A-MF, Wollenberg AC, Stuart LM, Stormo GD, Irazoqui JE. 2014. Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes. Immunity 40(6): 896– 909. 24882217 PMC4104614
  64. Ward LD, Kellis M. 2012. HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res. 40(Database issue): D930– D934. 22064851 PMC3245002
  65. Warner N, Burberry A, Pliakas M, McDonald C, Núñez G. 2014. A genome-wide small interfering RNA (siRNA) screen reveals nuclear factor-κB (NF-κB)-independent regulators of NOD2-induced interleukin-8 (IL-8) secretion. J Biol Chem. 289(41): 28213– 28224. 25170077 PMC4192477
  66. Wolf J, Passmore LA. 2014. mRNA deadenylation by Pan2–Pan3. Biochem Soc Trans. 42(1): 184– 187. 24450649 PMC3992365
  67. Yair S, Lee KM, Coop G. 2021. The timing of human adaptation from Neanderthal introgression. Genetics 218(1): iyab052. 33787889 PMC8128397
  68. Yu Y, Li C, Wang Y, Wang Q, Wang S, Wei S, Yang M, Qin Q. 2019. Molecular cloning and characterization of grouper Krüppel-like factor 9 gene: involvement in the fish immune response to viral infection. Fish Shellfish Immunol. 89: 677– 689. 30905839
  69. Zeberg H, Pääbo SA. 2020a. Genetic variant protective against severe COVID-19 is inherited from Neandertals. Available from: http://biorxiv.org/lookup/doi/10.1101/2020.10.05.327197. · DOI
  70. Zeberg H, Pääbo S. 2020b. The major genetic risk factor for severe COVID-19 is inherited from Neandertals. Available from: http://biorxiv.org/lookup/doi/10.1101/2020.07.03.186296 32998156 · DOI
  71. Zhang X, Witt KE, Bañuelos MM, Ko A, Yuan K, Xu S, Nielsen R, Huerta-Sanchez E. 2020. The history and evolution of the Denisovan-EPAS1 haplotype in Tibetans. Proc Natl Acad Sci U S A. 118(22): e2020803118. PMC8179186 34050022

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Authors
Jagoda, E., Xue, J. R., Reilly, S. K., Dannemann, M., Racimo, F., Huerta-Sanchez, E., Sankararaman, S., Kelso, J., Pagani, L., Sabeti, P. C., & Capellini, T. D.
Affiliations
  • Harvard University (US)
  • Broad Institute (US)
  • Max Planck Institute for Evolutionary Anthropology (DE)
  • University of Copenhagen (DK)
  • Department of Ecology and Evolutionary Biology, Brown University, Providence, RI, USA
  • University of California, Los Angeles (US)
  • University of Padua (IT)
Corresponding author
Capellini, Terence D
ORCID
Venue
Molecular Biology and Evolution
Publisher
Oxford University Press (OUP)
Published
2021-10-18
Volume
39
Issue
1
ISSN
  • 0737-4038 (ISSN-L)
  • 1537-1719
DOI
10.1093/molbev/msab304
PMC
PMC8760939
OpenAlex
W3206690965
Cited by
47
References
15
Citations by year
2026: 8 · 2025: 10 · 2024: 11 · 2023: 9 · 2022: 9
FWCI
4.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Biology and Evolution (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by)
Funders
  • National Science Foundation (F32HG00922, 1847287, 2020205, K99HG010669)
  • Harvard University
  • Villum Fonden (00025300)
  • European Commission (MOBEC008, 810645)
  • Lundbeckfonden (R302-2018-2155)
  • Max-Planck-Gesellschaft
  • National Institutes of Health (F32HG00922)
  • European Regional Development Fund (810645, MOBEC008)
  • National Human Genome Research Institute (K99HG010669)
  • National Institute of General Medical Sciences (R35GM125055, R35GM128946)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Social Sciences › Anthropology › Pleistocene-Era Hominins and Archaeology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
Keywords
Neanderthal introgression, adaptive introgression, cis-regulatory elements, massively parallel reporter assay, human immune cells, positive selection, COVID-19 protection, STAT2, influenza, innate immunity, neutrophil count, white blood cell count, regulatory variants
MeSH terms
Animals, Humans, Immunity, Innate, Inflammation, Genetic Variation, Gene Expression, Genome, Human, Neanderthals

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