Human Molecular Genetics Advance Access first published online on November 5, 2009
This version [Corrected Proof] published online on November 18, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddp505
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Genetic structure of a unique admixed population: implications for medical research
1 Broad Institute of MIT (Massachusetts Institute of Technology) and Harvard University, Cambridge Center, Cambridge, MA, USA, 2 Cancer Genetics Group, Children's Cancer Institute Australia for Medical Research, Sydney Children's Hospital, Randwick, NSW 2031, Australia, 3 University of the Western Cape, Cape Town, South Africa, 4 Eijkman Institute for Molecular Biology, Jakarta, Indonesia, 5 Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa, 6 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA and 7 Faculty of Medicine, University of New South Wales, Randwick, NSW 2031, Australia
* To whom correspondence should be addressed. Tel: +61 293820229; Fax: +61 293821850; Email: vhayes{at}ccia.unsw.edu.au
Received May 12, 2009; Revised September 29, 2009; Accepted October 29, 2009
Statement: In naming population groups, we think a chief aim is to use terms that the group members use themselves, or find familiar and comfortable. The terms used in this manuscript to describe populations are as historically correct as possible and are chosen so as not to offend any population group. Two of the authors (DCP and REvdR) belong to the Coloured population, with one of the authors (REvdR) having contributed extensively to current literature on the history of the Coloured people of South Africa and served as Vice-President of the South African Institute of Race Relations. According to the 2001 South African census (http://www.statssa.gov.za/census01/HTML/CInBrief/ CIB2001.pdf), ‘Statistics South Africa continues to classify people by population group, in order to monitor progress in moving away from the apartheid-based discrimination of the past. However, membership of a population group is now based on self-perception and self-classification, not on a legal definition. Five options were provided on the questionnaire, Black African, Coloured, Indian or Asian, White and Other. Responses in the category "Other" were very few and were therefore imputed’. We have elected to use the term Bushmen rather than San to refer to the hunter-gatherer people of Southern Africa. Although they have no collective name for themselves, this decision was based on the term Bushmen (or Bossiesman) being the more familiar to the communities themselves, while the term San is the more accepted academic classification.
Understanding human genetic structure has fundamental implications for understanding the evolution and impact of human diseases. In this study, we describe the complex genetic substructure of a unique and recently admixed population arising 
350 years ago as a direct result of European settlement in South Africa. Analysis was performed using over 900 000 genome-wide single nucleotide polymorphisms in 20 unrelated ancestry-informative marker selected Coloured individuals and made comparisons with historically predicted founder populations. We show that there is substantial genetic contribution from at least four distinct population groups: Europeans, South Asians, Indonesians and a population genetically close to the isiXhosa sub-Saharan Bantu. This is in good accord with the historical record. We briefly examine the implications of determining the genetic diversity of this population, not only for furthering understanding of human evolution out of Africa, but also for genome-wide association studies using admixture mapping. In conclusion, we define the genetic structure of a uniquely admixed population that holds great potential to advance genetic-based medical research.
These authors equally contributed to this work.