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Characterization of Extensive Diversity In Immunoglobulin Light Chain Variable Germline Genes Across Biomedically Important Mouse Strains

View ORCID ProfileJustin T. Kos, View ORCID ProfileYana Safonova, Kaitlyn M. Shields, Catherine A. Silver, View ORCID ProfileWilliam D. Lees, Andrew M. Collins, View ORCID ProfileCorey T. Watson
doi: https://doi.org/10.1101/2022.05.01.489089
Justin T. Kos
1Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA
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  • For correspondence: justin.kos@louisville.edu
Yana Safonova
2Department of Computer Science, Johns Hopkins University, Baltimore MD, USA
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Kaitlyn M. Shields
1Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA
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Catherine A. Silver
1Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA
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William D. Lees
3Institute of Structural and Molecular Biology, Birkbeck College, University of London, London, UK
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Andrew M. Collins
4School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia
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Corey T. Watson
1Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA
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  • For correspondence: justin.kos@louisville.edu
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Abstract

The light chain immunoglobulin genes of biomedically relevant mouse strains are poorly documented in current germline gene databases. We previously showed that IGH loci of wild-derived mouse strains representing the major mouse subspecies contained 247 germline IGHV sequences not curated in the international ImMunoGeneTics (IMGT) information system, which is the most commonly used database that curates the germline repertoires used for sequence alignment in AIRR-seq analysis. Despite containing levels of polymorphism similar to the IGH locus, the germline gene content and diversity of the light chain loci have not been comprehensively cataloged. To explore the extent of germline light chain repertoire diversity across mouse strains commonly used in the biomedical sciences, we performed AIRR-seq analysis and germline gene inference for 18 inbred mouse strains, including the four wild-derived strains with diverse sub-species origins. We inferred 1582 IGKV and 63 IGLV sequences, representing 459 and 22 unique IGKV and IGLV sequences. Of the unique inferred germline IGKV and IGLV sequences, 67.8% and 59%, respectively, were undocumented in IMGT. Across strains we observed germline IGKV sequences shared by three distinct IGK haplotypes and a more conserved IGLV germline repertoire. In addition, J gene inference indicated a novel IGK2 allele shared between PWD/PhJ and MSM/MsJ and a novel IGLJ1 allele for LEWES/EiJ and IGLJ2 allele for MSM/MsJ. Finally, a combined IGHV, IGKV, and IGLV phylogenetic analysis of wild-derived germline repertoires displayed reduced germline diversity for the light chain repertoire compared to the heavy chain repertoire, suggesting potential evolutionary differences between the two chains.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 01, 2022.
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Characterization of Extensive Diversity In Immunoglobulin Light Chain Variable Germline Genes Across Biomedically Important Mouse Strains
Justin T. Kos, Yana Safonova, Kaitlyn M. Shields, Catherine A. Silver, William D. Lees, Andrew M. Collins, Corey T. Watson
bioRxiv 2022.05.01.489089; doi: https://doi.org/10.1101/2022.05.01.489089
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Characterization of Extensive Diversity In Immunoglobulin Light Chain Variable Germline Genes Across Biomedically Important Mouse Strains
Justin T. Kos, Yana Safonova, Kaitlyn M. Shields, Catherine A. Silver, William D. Lees, Andrew M. Collins, Corey T. Watson
bioRxiv 2022.05.01.489089; doi: https://doi.org/10.1101/2022.05.01.489089

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