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

Lookup NU author(s): Dr Peter Middleton

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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. © 2004 Nature Publishing Group All rights reserved.


Publication metadata

Author(s): Spink CF, Keen LJ, Middleton PG, Bidwell JL

Publication type: Article

Publication status: Published

Journal: Genes and Immunity

Year: 2004

Volume: 5

Issue: 1

Pages: 76-79

ISSN (print): 1466-4879

ISSN (electronic): 1476-5470

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/sj.gene.6364039

DOI: 10.1038/sj.gene.6364039

PubMed id: 14735154


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