Abstract
The human population is undergoing a major transition from a historical metapopulation structure of relatively isolated small communities to an outbred structure. This process is predicted to increase average individual genome-wide heterozygosity (h) and could have effects on health. We attempted to quantify this increase in mean h. We initially sampled 1001 examinees from a metapopulation of nine isolated villages on five Dalmatian islands (Croatia). Village populations had high levels of genetic differentiation, endogamy and consanguinity. We then selected 166 individuals with highly specific personal genetic histories to form six subsamples, which could be ranked a priori by their predicted level of outbreeding. The measure h was then estimated in the 166 examinees by genotyping 1184 STR/indel markers and using two different computation methods. Compared to the value of mean h in the least outbred sample, values of h in the remaining samples increased successively with predicted outbreeding by 0.023, 0.038, 0.058, 0.067 and 0.079 (P<0.0001), where these values are measured on the same scale as the inbreeding coefficient (but opposite sign). We have shown that urbanisation was associated with an average increase in h of up to 0.08–0.10 in this Croatian metapopulation, regardless of the method used. Similar levels of differentiation have been described in many populations. Therefore, changes in the level of heterozygosity across the genome of this magnitude may be common during isolate break-up in humans and could have significant health effects through the established genetic mechanism of hybrid vigour/heterosis.
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Acknowledgements
Igor Rudan and Ozren Polasek were supported by Overseas Research Scheme and by the scholarship from the University of Edinburgh. Ozren Polasek is supported by the PhD scholarship from the University of Edinburgh. Igor Rudan and Zrinka Biloglav were supported by the British Scholarship Trust Fellowship. Zrinka Biloglav was supported by ‘Miroslav Cackovic’ fellowship of the Faculty of Medicine, University of Zagreb. The study was partially supported through the grants from the National Institutes of Health to Igor Rudan, Harry Campbell and James L Weber; Ministry of Science, Education and Sport of the Republic of Croatia to Igor Rudan (number 108-1080315-0302), and the grants from The British Council, The Wellcome Trust, The Royal Society and Medical Research Council to Harry Campbell and Igor Rudan and European Commission FP6 STRP grant number 018947 (LSHG-CT-2006-01947). The authors collectively thank medical students of the Faculty of Medicine, University of Zagreb, Croatia; local general practitioners and nurses in study populations; the employees of several other Croatian institutions, including but not limited to the Institute for Anthropological Research in Zagreb, Croatia; the University of Rijeka and Split, Croatia; Croatian Institute of Public Health; Institutes of Public Health in Split and Dubrovnik, Croatia for their individual help in planning and carrying out the field work related to the project.
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Rudan, I., Carothers, A., Polasek, O. et al. Quantifying the increase in average human heterozygosity due to urbanisation. Eur J Hum Genet 16, 1097–1102 (2008). https://doi.org/10.1038/ejhg.2008.48
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DOI: https://doi.org/10.1038/ejhg.2008.48
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