Northampton Electronic Collection of Theses and Research

A worldwide analysis of beta-defensin copy number variation suggests recent selection of a high-expressing DEFB103 gene copy in East Asia

Hardwick, R. J., Machado, L., Zuccherato, L., Antolinos, S., Xue, Y., Shawa, N., Gilman, R., Cabrera, L., Berg, D., Tyler-Smith, C., Kelly, P., Tarazona-Santos, E. and Hollox, E. J. (2011) A worldwide analysis of beta-defensin copy number variation suggests recent selection of a high-expressing DEFB103 gene copy in East Asia. Human Mutation. 32(7), pp. 743-750. 1059-7794.

Item Type: Article
Abstract: Beta-defensins are a family of multifunctional genes with roles in defense against pathogens, reproduction, and pigmentation. In humans, six beta-defensin genes are clustered in a repeated region which is copy-number variable (CNV) as a block, with a diploid copy number between 1 and 12. The role in host defense makes the evolutionary history of this CNV particularly interesting, because morbidity due to infectious disease is likely to have been an important selective force in human evolution, and to have varied between geographical locations. Here, we show CNVof the beta-defensin region in chimpanzees, and identify a beta-defensin block in the human lineage that contains rapidly evolving noncoding regulatory sequences. We also show that variation at one of these rapidly evolving sequences affects expression levels and cytokine responsiveness of DEFB103, a key inhibitor of influenza virus fusion at the cell surface. A worldwide analysis of betadefensin CNV in 67 populations shows an unusually high frequency of high-DEFB103-expressing copies in East Asia, the geographical origin of historical and modern influenza epidemics, possibly as a result of selection for increased resistance to influenza in this region.
Uncontrolled Keywords: CNV, defensin, antimicrobial, influenza, paralogue ratio test
Subjects: R Medicine > RB Pathology > RB151 Theories of disease. Etiology. Pathogenesis > RB155 Medical genetics
Q Science > QH Natural history > QH426 Genetics > QH438.7 Human genetics
R Medicine > RA Public aspects of medicine > RA643 Disease (Communicable and non-infectious) and public health
Creators: Hardwick, Robert J, Machado, Lee, Zuccherato, Luciana, Antolinos, Suzanne, Xue, Yali, Shawa, Nyambura, Gilman, Robert, Cabrera, Lilia, Berg, Douglas, Tyler-Smith, Chris, Kelly, Paul, Tarazona-Santos, Eduardo and Hollox, Edward J
Publisher: John Wiley & Sons
Northamptonshire and East Midlands: Health
Faculties, Divisions and Institutes: University Faculties, Divisions and Research Centres - OLD > Faculty of Health & Society
University Faculties, Divisions and Research Centres - OLD > Research Centre > Institute of Health and Wellbeing > Ageing Research Centre
Research Centres > Centre for Health Sciences and Services
Research Centres > Centre for Physical Activity and Life Sciences
Date: July 2011
Date Type: Publication
Page Range: pp. 743-750
Journal or Publication Title: Human Mutation
Volume: 32
Number: 7
Language: English
ISSN: 1059-7794
Status: Published / Disseminated

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