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Prevalence and evolutionary origins of autoimmune susceptibility alleles in natural mouse populations

Genes & Immunity volume 9, pages 61–68 (2008)Cite this article

Abstract

The evolutionary origin of genetic diversity in the SLAM/CD2 gene cluster, implicated in autoimmune lupus susceptibility in mice, was investigated by sequence analysis of exons from six members of the cluster in 48 wild mouse samples derived from the global mouse population. A total of 80 coding region SNPs were identified among the six genes analyzed, indicating that this gene cluster is highly polymorphic in natural mouse populations. Phylogenetic analyses of these allelic sequences revealed clustering of alleles derived from multiple Mus species and subspecies, indicating alleles at several SLAM/CD2 loci were present in ancestral Mus populations prior to speciation and have persisted as polymorphisms for more than 1 million years. Analyses of nonsynonymous/synonymous ratios using likelihood codon substitution models identified several segments in Cd229, Cd48 and Cd84 that were impacted by positive diversifying selective pressures. These findings support the interpretation that selection favoring the generation and retention of functional polymorphisms has played a role in the evolutionary origin of genetic polymorphisms that are predisposing to autoimmunity.

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Acknowledgements

Support for these studies was provided by grants from the National Institute of Allergy and Infectious Disease to EKW. NL and KB were supported by NIH training grant no. NIH T32 AI 005284. FB was supported by ISEM 2007-084.

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Authors and Affiliations

  1. Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    N Limaye, K A Belobrajdic, A E Wandstrat & E K Wakeland

  2. CNRS-UMR 5172, Universite MontpellierII, Montpellier, France

    F Bonhomme

  3. Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA

    S V Edwards

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  1. N Limaye
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  2. K A Belobrajdic
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  3. A E Wandstrat
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  4. F Bonhomme
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  6. E K Wakeland
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Correspondence to E K Wakeland.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Limaye, N., Belobrajdic, K., Wandstrat, A. et al. Prevalence and evolutionary origins of autoimmune susceptibility alleles in natural mouse populations. Genes Immun 9, 61–68 (2008). https://doi.org/10.1038/sj.gene.6364446

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