The HLA-B*57:01 allele corresponds to a very large MHC haploblock likely explaining its massive effect for HIV-1 elite control

IntroductionWe have reanalyzed the genomic data of the International Collaboration for the Genomics of HIV (ICGH), centering on HIV-1 Elite Controllers.MethodsWe performed a genome-wide Association Study comparing 543 HIV Elite Controllers with 3,272 uninfected controls of European descent. Using the latest database for imputation, we analyzed 35,552 Single Nucleotide Polymorphisms (SNPs) within the Major Histocompatibility Complex (MHC) region.ResultsOur analysis identified 2,626 SNPs significantly associated (p<5. 10-8) with elite control of HIV-1 infection, including well-established MHC signals such as the rs2395029-G allele which tags HLA-B*57:01. A thorough investigation of SNPs in linkage disequilibrium with rs2395029 revealed an extensive haploblock spanning 1.9 megabases in the MHC region tagging HLA-B*57:01, comprising 379 SNP alleles impacting 72 genes. This haploblock contains damaging variations in proteins like NOTCH4 and DXO and is also associated with a strong differential pattern of expression of multiple MHC genes such as HLA-B, MICB, and ZBTB12. The study was expanded to include two cohorts of seropositive African-American individuals, where a haploblock tagging the HLA-B*57:03 allele was similarly associated with control of viral load. The mRNA expression profile of this haploblock in African Americans closely mirrored that in the European cohort.DiscussionThese findings suggest that additional molecular mechanisms beyond the conventional antigen-presenting role of class I HLA molecules may contribute to the observed influence of HLA-B*57:01/B*57:03 alleles on HIV-1 elite control. Overall, this study has uncovered a large haploblock associated with HLA-B*57 alleles, providing novel insights into their massive effect on HIV-1 elite control

A human leukocyte antigen imputation study uncovers possible genetic interplay between gut inflammatory processes and autism spectrum disorders

Autism spectrum disorders (ASD) are neurodevelopmental conditions that are for subsets of individuals, underpinned by dysregulated immune processes, including inflammation, autoimmunity, and dysbiosis. Consequently, the major histocompatibility complex (MHC)-hosted human leukocyte antigen (HLA) has been implicated in ASD risk, although seldom investigated. By utilizing a GWAS performed by the EU-AIMS consortium (LEAP cohort), we compared HLA and MHC genetic variants, single nucleotide polymorphisms (SNP), and haplotypes in ASD individuals, versus typically developing controls. We uncovered six SNPs, namely rs9268528, rs9268542, rs9268556, rs14004, rs9268557, and rs8084 that crossed the Bonferroni threshold, which form the underpinnings of 3 independent genetic pathways/blocks that differentially associate with ASD. Block 1 (rs9268528-G, rs9268542-G, rs9268556-C, and rs14004-A) afforded protection against ASD development, whilst the two remaining blocks, namely rs9268557-T, and rs8084-A, associated with heightened risk. rs8084 and rs14004 mapped to the HLA-DRA gene, whilst the four other SNPs located in the BTNL2 locus. Different combinations amongst BTNL2 SNPs and HLA amino acid variants or classical alleles were found either to afford protection from or contribute to ASD risk, indicating a genetic interplay between BTNL2 and HLA. Interestingly, the detected variants had transcriptional and/or quantitative traits loci implications. As BTNL2 modulates gastrointestinal homeostasis and the identified HLA alleles regulate the gastrointestinal tract in celiac disease, it is proposed that the data on ASD risk may be linked to genetically regulated gut inflammatory processes. These findings might have implications for the prevention and treatment of ASD, via the targeting of gut-related processes

Seasonal and environmental variations influencing the Varroa Sensitive Hygiene trait in the honey bee

International audienceThe invasive miteVarroa destructor is identified as the main biotic cause of European honey bee colony losses in many regions, leading to systematic treatments of colonies every year in order to prevent colonies from collapsing. However, some colonies have been reported to survive in the absence of treatment. The ability of honey bee colonies to survive varroa mite infestations has been associated with the development of Varroa Sensitive Hygiene (VSH) behavior. Colonies displaying VSH are able to detect the presence of varroa through the cap of developing brood cells and to remove the parasitized brood. To improve breeding programs for varroa resistance in apiculture, detailed knowledge of the mechanisms that enable bees to survive mite infestation and environmental conditions that can influence the expression and phenotyping of VSH behavior are needed. This study evaluated the influence of the genetic origin of the colony, the colony population dynamics, varroa density, and food supply on the ability of colonies to express the VSH trait. First, we found that varroa-selected colonies displayed lower varroa population growth rate. We also revealed that the genetic origin of the colonies and the month during which the test was performed had a significant impact on VSH behavior, with varroa-selected colonies showing higher VSH abilities than unselected colonies, and especially at the end of summer. Finally, we showed that sedentary varroa-selected colonies expressed higher VSH activity than colonies placed on lavender fields during active honey flow. Such findings are particularly important to standardize testing for varroa resistant colonies in different locations, a feature that is essential to ensure the success of breeding efforts

Caractérisation d'épisodes de pollution particulaire observés in situ sur la plateforme d'observations de Lille

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Nitrogen cycle inferred from N and O isotopes in a changing Arctic Ocean

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New Particle Formation observed in the close vicinity of a French megalopolis

International audienc

New Particle Formation observed in the close vicinity of a French megalopolis

International audienc