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  1. Article ; Online: Genetic adaptation to pathogens and increased risk of inflammatory disorders in post-Neolithic Europe

    Gaspard Kerner / Anna-Lena Neehus / Quentin Philippot / Jonathan Bohlen / Darawan Rinchai / Nacim Kerrouche / Anne Puel / Shen-Ying Zhang / Stéphanie Boisson-Dupuis / Laurent Abel / Jean-Laurent Casanova / Etienne Patin / Guillaume Laval / Lluis Quintana-Murci

    Cell Genomics, Vol 3, Iss 2, Pp 100248- (2023)

    2023  

    Abstract: Summary: Ancient genomics can directly detect human genetic adaptation to environmental cues. However, it remains unclear how pathogens have exerted selective pressures on human genome diversity across different epochs and affected present-day ... ...

    Abstract Summary: Ancient genomics can directly detect human genetic adaptation to environmental cues. However, it remains unclear how pathogens have exerted selective pressures on human genome diversity across different epochs and affected present-day inflammatory disease risk. Here, we use an ancestry-aware approximate Bayesian computation framework to estimate the nature, strength, and time of onset of selection acting on 2,879 ancient and modern European genomes from the last 10,000 years. We found that the bulk of genetic adaptation occurred after the start of the Bronze Age, <4,500 years ago, and was enriched in genes relating to host-pathogen interactions. Furthermore, we detected directional selection acting on specific leukocytic lineages and experimentally demonstrated that the strongest negatively selected candidate variant in immunity genes, lipopolysaccharide-binding protein (LBP) D283G, is hypomorphic. Finally, our analyses suggest that the risk of inflammatory disorders has increased in post-Neolithic Europeans, possibly because of antagonistic pleiotropy following genetic adaptation to pathogens.
    Keywords ancient DNA ; immunity ; host defense ; natural selection ; local adaptation ; inflammatory disorders ; Genetics ; QH426-470 ; Internal medicine ; RC31-1245
    Subject code 930
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Human inherited complete STAT2 deficiency underlies inflammatory viral diseases

    Giorgia Bucciol / Leen Moens / Masato Ogishi / Darawan Rinchai / Daniela Matuozzo / Mana Momenilandi / Nacim Kerrouche / Catherine M. Cale / Elsa R. Treffeisen / Mohammad Al Salamah / Bandar K. Al-Saud / Alain Lachaux / Remi Duclaux-Loras / Marie Meignien / Aziz Bousfiha / Ibtihal Benhsaien / Anna Shcherbina / Anna Roppelt / COVID Human Genetic Effort /
    Florian Gothe / Nadhira Houhou-Fidouh / Scott J. Hackett / Lisa M. Bartnikas / Michelle C. Maciag / Mohammed F. Alosaimi / Janet Chou / Reem W. Mohammed / Bishara J. Freij / Emmanuelle Jouanguy / Shen-Ying Zhang / Stephanie Boisson-Dupuis / Vivien Béziat / Qian Zhang / Christopher J.A. Duncan / Sophie Hambleton / Jean-Laurent Casanova / Isabelle Meyts

    The Journal of Clinical Investigation, Vol 133, Iss

    2023  Volume 12

    Abstract: STAT2 is a transcription factor activated by type I and III IFNs. We report 23 patients with loss-of-function variants causing autosomal recessive (AR) complete STAT2 deficiency. Both cells transfected with mutant STAT2 alleles and the patients’ cells ... ...

    Abstract STAT2 is a transcription factor activated by type I and III IFNs. We report 23 patients with loss-of-function variants causing autosomal recessive (AR) complete STAT2 deficiency. Both cells transfected with mutant STAT2 alleles and the patients’ cells displayed impaired expression of IFN-stimulated genes and impaired control of in vitro viral infections. Clinical manifestations from early childhood onward included severe adverse reaction to live attenuated viral vaccines (LAV) and severe viral infections, particularly critical influenza pneumonia, critical COVID-19 pneumonia, and herpes simplex virus type 1 (HSV-1) encephalitis. The patients displayed various types of hyperinflammation, often triggered by viral infection or after LAV administration, which probably attested to unresolved viral infection in the absence of STAT2-dependent types I and III IFN immunity. Transcriptomic analysis revealed that circulating monocytes, neutrophils, and CD8+ memory T cells contributed to this inflammation. Several patients died from viral infection or heart failure during a febrile illness with no identified etiology. Notably, the highest mortality occurred during early childhood. These findings show that AR complete STAT2 deficiency underlay severe viral diseases and substantially impacts survival.
    Keywords Immunology ; Medicine ; R
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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