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bioRxiv · 10.1101/2025.07.18.665479

IMGT(R) Analysis of the Human IGH Locus: Unveiling Novel Polymorphisms and Copy Number Variations in Genome Assemblies from Diverse Ancestral Backgrounds

Papadaki, A.·Georga, M.·Jabado-Michaloud, J.·Folch, G.·Zeitoun, G.·Duroux, P.·Giudicelli, V.·Kossida, S.
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Abstract

Unraveling the genetic complexity of the human immunoglobulin heavy chain (IGH) locus provides valuable insights into the mechanisms underlying the efficacy and specificity of the adaptive immune response. Despite its crucial role, the IGH locus remains insufficiently characterized, with its allelic diversity and polymorphisms inadequately investigated. In this study, we present an analysis of the human IGH locus, incorporating 15 human genome assemblies from diverse ancestries, including African, European, Asian, Saudi, and mixed backgrounds. Through our examination of both maternal and paternal assemblies, we uncover novel IGH alleles, copy number variations (CNV), and polymorphisms, particularly within the variable (IGHV) region. Our findings reveal extensive and previously uncharacterized genetic variability in the constant (IGHC) region and distinct IMGT CNV forms across individuals. This research contributes to a significant enrichment of the IMGT(R) IGH reference directory, databases, tools and web resources and lays the groundwork for a comprehensive IMGT(R) haplotype database which can be progressively enriched to support future studies in population-specific immune profiles and adaptive immune related disease susceptibility, as comprehensive datasets become available. Such a resource promises to propel personalized immunogenomics forward, with exciting applications in cancer immunotherapy, COVID-19, and other immune-related diseases. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=82 SRC="FIGDIR/small/665479v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@17afc2corg.highwire.dtl.DTLVardef@141d785org.highwire.dtl.DTLVardef@1ac7500org.highwire.dtl.DTLVardef@13558fc_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Papadaki, A., Georga, M., Jabado-Michaloud, J., Folch, G., Zeitoun, G., Duroux, P., Giudicelli, V., Kossida, S.. 2025-07-22. IMGT(R) Analysis of the Human IGH Locus: Unveiling Novel Polymorphisms and Copy Number Variations in Genome Assemblies from Diverse Ancestral Backgrounds. https://doi.org/10.1101/2025.07.18.665479

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