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An investigation of transmission ratio distortion in the central region of the human MHC

Genes & Immunity volume 7, pages 51–58 (2006)Cite this article

Abstract

Transmission ratio distortion (TRD) describes a significant departure from expected Mendelian inheritance ratios that is fundamental to both the biology of reproduction and statistical genetics. The relatively high fetal wastage in humans, with consequent selection of alleles in utero, makes it likely that TRD is prevalent in the human genome. The central region of the human major histocompatibility complex (MHC) is a strong TRD candidate, as it houses a number of immune and regulatory genes that may be important in pregnancy outcome. We used a nonhaplotype-based method to select 13 tagging SNPs from three central MHC candidate regions, and analysed their transmission in 380 newborns and their parents (1138 individuals). A TRD of 54:46 was noted in favour of the common allele of a promoter SNP in the CLIC1 gene (P=0.025), with a similar distortion using haplotypes across the same gene region (P=0.016). We also found evidence that markers in the CLIC1 gene region may have been subject to recent selection (P<0.001). The study illustrates the potential benefits of screening for TRD and highlights the difficulties encountered therein.

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Acknowledgements

We thank Zahra Madgwick and Jan Tinder for their assistance with patient recruitment and sample collation. We also thank Dr Jonathan Pritchard (University of Chicago) for his helpful comments and ideas. NH was supported in this work by a scholarship from the Rhodes Trust, UK. This study was financially supported with the help of an Oxfordshire Health Services Research Grant to MH, and through the Medical Research Council, UK.

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Authors and Affiliations

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

    N Hanchard, K Rockett, I Udalova, J Wilson, B Keating, O Koch, A Nijnik, M Diakite & D Kwiatkowski

  2. Department of Paediatrics, University of Oxford, Oxford, UK

    N Hanchard, K Rockett, J Wilson, M Herbert & D Kwiatkowski

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  1. N Hanchard
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  2. K Rockett
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  3. I Udalova
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Correspondence to N Hanchard.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gene)

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Hanchard, N., Rockett, K., Udalova, I. et al. An investigation of transmission ratio distortion in the central region of the human MHC. Genes Immun 7, 51–58 (2006). https://doi.org/10.1038/sj.gene.6364277

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