1. ¹Department of Pathology and Microbiology, University of Bristol, UK
2. ²Department of Haematology, School of Clinical Laboratory Sciences, University of Newcastle, UK

Correspondence: Miss C Spink, Department of Pathology and Microbiology, University of Bristol, Homoeopathic Hospital Site, Cotham, Bristol BS6 6JU, UK. E-mail: C.F.Spink@bristol.ac.uk

Received 7 August 2003; Revised 2 October 2003; Accepted 3 October 2003.

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.