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Polymorphisms of NKG2D ligands: diverse RAET1/ULBP genes in Northeastern Thais

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Abstract

Unique long 16 (UL-16)-binding proteins (ULBP) or retinoic acid early transcripts-1 (RAET1) are ligands to the activating receptor, NKG2D. The human RAET1/ULBP gene family is identified as ten members (RAET1E to N) with six loci encoding for potentially functional proteins. These are ULBP1 or RAET1I, ULBP2 or RAET1H, ULBP3 or RAET1N, and RAET1L, which are glycosylinositol phospholipid (GPI)-linked glycoproteins and ULBP4 or RAET1E and ULBP5 or RAET1G, which are transmembrane glycoproteins. The RAET1 products contain the α1 and α2 domains but lack the α3 domain and do not associate with β2-microglobulin. RAET1/ULBPs have tissue-specific expressions, and some of them are also polymorphic. In the present study, polymorphic exons 2 and 3 of the RAET1E, G, H, I, L, and N were analyzed using sequence-based typing. One hundred and seventy-six unrelated healthy Northeastern Thais were included in this study. For RAET1E, RAET1G, RAET1H, and RAET1L, there were seven, two, five, and four single nucleotide polymorphisms (SNPs), respectively. Six of these are new SNPs, which are rare in this population. Of these, six new SNPs, two of two in RAET1E, two of three in RAET1H, and none of one in RAET1L are nonsynonymous substitutions. Interestingly, although the RAET1N is polymorphic in Caucasians, RAET1N and RAET1I had no variation in Thais indicating diverse RAET1 genes in different ethnic groups. These data provide the important basis for future analysis on the role of RAET1 genes in immune responses especially in cancer and infectious diseases.

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Acknowledgements

This research was supported by the Department of Genetic Information, Division of Molecular Life Science, Tokai University School of Medicine, Japan and the Centre for Research and Development of Medical Diagnostic Laboratory (CMDL), Khon Kaen University. The authors thank Professor James Will for assistance with the English and the presentation of the manuscript and Dr. Anavaj Sakuntabhai, Pasteur Institute, Paris, France for additional samples, support, and assistance in SNP typing. CL was a Thailand Research Fund (TRF) Scholar and SR is holding a Royal Golden Jubilee Scholarship (RJG) supported by TRF.

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Correspondence to Chanvit Leelayuwat.

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Romphruk, A.V., Romphruk, A., Naruse, T.K. et al. Polymorphisms of NKG2D ligands: diverse RAET1/ULBP genes in Northeastern Thais. Immunogenetics 61, 611–617 (2009). https://doi.org/10.1007/s00251-009-0394-7

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  • DOI: https://doi.org/10.1007/s00251-009-0394-7

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