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Diversity in the preimmune immunoglobulin repertoire of SHR lines susceptible and resistant to end-organ injury

Genes & Immunity volume 15, pages 528–533 (2014)Cite this article

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Abstract

We used next-generation sequencing to identify immunoglobulin heavy chain (IGH) genetic variation in two closely related hypertensive rat lines that differ in susceptibility to end-organ disease (SHR-A3 and SHR-B2). The two SHR lines differ extensively at the IGH locus from the rat reference genome sequence and from each other, creating 306 sequence unique IGH genes. Compared with IGH genes mapped in the rat reference genome sequence, 98 are null gene alleles (31 are null in both SHR lines, 45 are null in SHR-A3 only and 23 are null in SHR-B2 only). Of the 306 divergent gene sequences, 126 result in amino acid substitution and, among these, SHR-A3 and SHR-B2 differ from one another at the amino acid level in 96 segments. Twelve pseudogenes in the rat reference genome sequence had changes displacing the stop codon and creating probable functional genes in either or both SHR-A3 and SHR-B2. A further five alleles that encoded functional rat reference genome sequence genes or open reading frames were converted to pseudogenes in either or both SHR-A3 and SHR-B2. These studies reveal that the preimmune immunoglobulin repertoire is highly divergent among SHR lines differing in end-organ injury susceptibility and this may modify immune mechanisms in hypertensive renal injury.

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Acknowledgements

The work reported has been supported by grants from NIH (R01DK069632-05 and R01DK081866) to PAD. PAD is grateful for additional endowed support from the Cullen Chair in Molecular Medicine at the University of Texas HSC Houston that provided support for rat genomic DNA sequencing.

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Authors and Affiliations

  1. Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA

    M L Gonzalez-Garay, S M Cranford, M C Braun & P A Doris

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  1. M L Gonzalez-Garay
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  2. S M Cranford
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  3. M C Braun
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  4. P A Doris
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Correspondence to P A Doris.

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Gonzalez-Garay, M., Cranford, S., Braun, M. et al. Diversity in the preimmune immunoglobulin repertoire of SHR lines susceptible and resistant to end-organ injury. Genes Immun 15, 528–533 (2014). https://doi.org/10.1038/gene.2014.40

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