Abstract
BackgroundDeviations from Hardy-Weinberg equilibrium (HWE) are commonly thought of as indicating genotyping errors, population stratification or some other artefact. However they could also arise through important biological mechanisms. In particular, genetic variants having a recessive effect on the successful fertilisation and/or development of an embryo might be manifest through such deviations in an unselected sample of "control" subjects.FindingsWe investigated genotypes from 463842 autosomal markers from 1504 British subjects. We identified regions in which several neighbouring markers exhibited deviation from HWE in the same direction by considering "heterozygosity scores" in windows of 10 markers. The heterozygosity score for each marker was defined as -log(p) or log(p) according to whether the marker demonstrated increased heterozygosity or homozygosity. In each window the marker with the highest absolute score was ignored and the positive and negative scores were summed for the other nine markers. Windows were selected on the basis of this sum exceeding a given threshold, for which we used values of 50 or 15.For the threshold of 50, we identified 7 regions with increased heterozygosity and for the threshold of 15 we identified 22 regions with increased heterozygosity, 23 with increased homozygosity and 2 containing both kinds of window. The most impressive of these results came from a group of 6 markers at 17q21, each of which showed increased heterozygosity significant at p < 10-190.ConclusionThe human genome contains regions which deviate markedly from HWE and these might harbour genes influencing embryonic survival.
Highlights
Deviations from Hardy-Weinberg equilibrium (HWE) are commonly thought of as indicating genotyping errors, population stratification or some other artefact
When marker allele frequencies in controls deviate markedly from Hardy-Weinberg equilibrium (HWE) this is commonly taken as an indicator that the genotyping is unreliable or that there is marked population stratification and the marker is discarded [1]
We reasoned that if groups of nearby markers all showed deviation from HWE this could not result purely from genotyping errors since there would be no reason for the same kind of error to be repli
Summary
Deviations from Hardy-Weinberg equilibrium (HWE) are commonly thought of as indicating genotyping errors, population stratification or some other artefact. Conclusion: The human genome contains regions which deviate markedly from HWE and these might harbour genes influencing embryonic survival.
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