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Direct sequence comparison of two divergent class I MHC natural killer cell receptor haplotypes

Genes & Immunity volume 6, pages 71–83 (2005)Cite this article

Abstract

The murine Ly49 gene family encoding natural killer cell receptors for class I MHC is an example of a rapidly evolving cluster of immune response genes. Determining the genomic sequence of the 129S6/SvEvTac (129S6) Ly49 cluster and comparing it to the known sequence of the C57BL/6 (B6) region provided insight into the mechanisms of Ly49 gene evolution. 129S6 contains 20 Ly49, many of which are pseudogenes and 40% of the genes have no counterpart in the B6 genome. The difference in gene content between these two strains is primarily the result of distinct patterns of gene duplication. Phylogenetic analyses of individual exons showed that Ly49 genes form distinct sub-families and an ancestral haplotype can be surmised. Dotplot analysis supports limited allelism in the two haplotypes; however, large regions of variation punctuate these islands of co-linearity. These variable regions contain a high concentration of repetitive elements that are predicted to contribute to the dynamic evolution of this cluster. The extreme variation in Ly49 haplotype content between mouse strains provides a genetic explanation for the documented differences in natural killer cell phenotype, and also indicates that differences in natural killer cell function observed between B6 and 129-derived gene-targeted mice should be interpreted with caution.

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Acknowledgements

We gratefully acknowledge Gary Levesque for BAC subcloning and subclone sequencing, Carole Dore and Xiaolan Zhang for BAC end sequencing, Vince Forgetta for bioinformatics support, Etienne Rousselle for performing pulse-field gel electrophoresis, and Brian Wilhelm for assistance with sequence analysis and critical reading of the manuscript. This project has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1CO12400. This work was also supported in part by an operating grant from the Canadian Institutes for Health Research. APM is a scholar of the Canadian Institutes for Health Research (New Investigator Award).

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Authors and Affiliations

  1. Laboratory of Molecular Immunology, IRCM, Montréal, QC, Canada

    A P Makrigiannis, D Patel & M-L Goulet

  2. Department of Medicine, Université de Montréal, Montréal, QC, Canada

    A P Makrigiannis

  3. Department of Medicine, Division of Experimental Medicine,

    A P Makrigiannis

  4. Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada

    A P Makrigiannis

  5. Department of Human Genetics, McGill University, McGill University and Genome Québec Innovation Centre, Montréal, QC, Canada

    K Dewar

  6. Basic Research Program, SAIC-Frederick, National Cancer Institute-Frederick, Frederick, MD, USA

    S K Anderson

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Correspondence to A P Makrigiannis.

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By acceptance of this article, the publisher or recipient acknowledges the right of the US Government to retain a nonexclusive, royalty-free license in and to any copyright covering the article.

Animal care was provided in accordance with the procedures outlined in ‘A Guide for the Care and Use of Laboratory Animals’ (National Institutes of Health Publication No. 86-23, 1985).

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Makrigiannis, A., Patel, D., Goulet, ML. et al. Direct sequence comparison of two divergent class I MHC natural killer cell receptor haplotypes. Genes Immun 6, 71–83 (2005). https://doi.org/10.1038/sj.gene.6364154

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