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Haplotypic relationship between SNP and microsatellite markers at the NOS2A locus in two populations

Genes & Immunity volume 4, pages 506–514 (2003)Cite this article

Abstract

The density of genetic markers required for successful association mapping of complex diseases depends on linkage disequilibrium (LD) between non-functional markers and functional variants. The haplotypic relationship between stable markers and potentially unstable but highly informative markers (e.g. microsatellites) indicates that LD might be maintained over considerable genetic distance in non-African populations, supporting the use of such ‘mixed marker haplotypes’ in LD-based mapping, and allowing inferences to be drawn about human origins. We investigated sequence variation in the proximal 2.6 kb of the inducible nitric oxide synthase (NOS2A) promoter and the relationship between SNP haplotypes and a pentanucleotide microsatellite (the ‘NOS2A−2.6 microsatellite’) in Gambians and UK Caucasians. UK Caucasians exhibited a subset of sequence diversity observed in Gambians, sharing four of 11 SNPs and a similar haplotypic structure. Five SNPs were found in the sequence of interspersed repetitive DNA elements. In both populations, there was dramatic loss of LD between SNP haplotypes and microsatellite alleles across a very short physical distance, suggesting a high intrinsic mutation rate of the NOS2A−2.6 microsatellite, the SNP haplotypes are relatively ancient, or that this was a region of frequent recombination. Understanding locus- and population-specific LD is essential when designing and interpreting genetic association studies.

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Acknowledgements

The authors thank Rosalind Harding, David Goldstein, Chris Tyler-Smith, John Armour, Dawn Field and Darren Irwin for stimulating discussions of the data. This work was financially supported by the Medical Research Council (UK).

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Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    D Burgner, K Rockett, H Ackerman, J Hull & D P Kwiatkowski

  2. Medical Research Council Laboratories, Fajara, The Gambia

    S Usen & M Pinder

  3. School of Paediatrics and Child Health, University of Western Australia, Perth, Australia

    D Burgner

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  1. D Burgner
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Correspondence to D Burgner.

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Burgner, D., Rockett, K., Ackerman, H. et al. Haplotypic relationship between SNP and microsatellite markers at the NOS2A locus in two populations. Genes Immun 4, 506–514 (2003). https://doi.org/10.1038/sj.gene.6364022

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