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Discrimination of suballeles present at the TNFd microsatellite locus using induced heteroduplex analysis

Genes & Immunity volume 5, pages 76–79 (2004)Cite this article

Abstract

Polymorphism at the TNFd locus has been implicated in a number of disease association studies. The TNFd locus consists of three regions of (GA)n repeats separated by an imperfect repeat of two guanine bases. TNFd alleles are genotyped by the number of repeats in the first (GA)n repeat region, and until now the second repeat region had been thought to be nonpolymorphic. We report the existence of suballeles present within the TNFd microsatellite locus, detected using induced heteroduplex generator (IHG) technology. These alleles cannot be detected using conventional typing strategies as they represent altered distribution of the (GA)n repeats or sequence variation within the repeat. The suballeles affect the frequencies of the conventional d3 and d4 alleles leading to significantly altered allele frequencies. Some studies have associated the d3 and d4 alleles with disease outcome. We re-analysed one such study cohort using IHG technology and demonstrated a high proportion of incorrectly assigned TNFd3 alleles.

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Acknowledgements

We would like to thank Dr. Nigel Wood for synthesis of the IHG reagents, and Doris Culpan for her help with the nucleotide sequencing.

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Authors and Affiliations

  1. Department of Pathology and Microbiology, University of Bristol, UK

    C F Spink, L J Keen & J L Bidwell

  2. Department of Haematology, School of Clinical Laboratory Sciences, University of Newcastle, UK

    P G Middleton

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  1. C F Spink
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  2. L J Keen
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  3. P G Middleton
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  4. J L Bidwell
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Correspondence to C F Spink.

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Spink, C., Keen, L., Middleton, P. et al. Discrimination of suballeles present at the TNFd microsatellite locus using induced heteroduplex analysis. Genes Immun 5, 76–79 (2004). https://doi.org/10.1038/sj.gene.6364039

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