Mapping the sickle cell gene

A team of geographers, biologists and statisticians produce the first detailed global map of the distribution of the sickle cell gene...

At a global scale, the sickle cell gene is most commonly found in areas with historically high levels of malaria, adding geographical support to the hyphothesis that the gene, whilst potentially deadly, avoids disappearing through natural selection by providing protection against malaria.

In a study funded by the Wellcome Trust, geographers, biologists and statisticians at the University of Oxford, together with colleagues from the KEMRI-Wellcome Trust Research Programme in Kenya, have produced the first detailed global map showing the distribution of the sickle cell gene. The results are published today in open access in the journal, Nature Communications.

Haemoglobin S (HbS) is known to cause sickle cell disease, which is usually fatal if untreated. Natural selection suggests that such a disadvantageous gene should not survive, yet it is common in people of African, Meditarranean and Indian origin.

More than sixty years ago, researchers observed that the sickle cell gene tended to be more common in populations living in, or originating from, areas of high malaria prevalence. This led to the 'malaria hypothesis', which suggested that, although deadly when inherited from both parents, the gene provided a degree of protection from malaria in children inheriting it from just one parent. This protective advantage was strong enough in areas of intense malaria transmission for the gene to survive.

The malaria hypothesis has since been supported by both population and laboratory studies, but the original observations of a geographical overlap between frequency of the gene and malaria prevalence have never been tested beyond simple visual comparisons at the global scale.

To address this, Dr Fred Piel and colleagues collated all the information currently accessible on the occurence of the sickle cell gene in native populations worldwide and, using modern mapping techniques, created a map of the global frequency of this gene. The map was then compared with the distribution and intensity of malaria before widespread malaria control.

The study showed that the sickle cell gene is most common in sub-Saharan Africa, the Middle East and India, and that the areas of high frequency of this gene are coincident with historically high levels of malaria, thus confirming that the malaria hypothesis is correct at the global scale.

''This study highlights the first steps in our efforts to create an open-access, online database of the frequency of various inherited blood disorders,'' says lead author Dr Piel, from the University of Oxford. ''Such databases will help improve estimates of their public health burden and guide where resources would be best applied.''

Co-author Dr Simon Hay adds: '' The malaria hyphothesis is the text-book example of a natural selection 'balancing act', where selection against an unfavourable mutation is weighed against selection in favour of a protective gene.''

The sickle frequency map was created as part of the activities of the Malaria Atlas Project, a multinational research collaboration funded primarily by the Wellcome Trust. Further information about the Malaria Atlas Project can be found at www.map.ox.ac.uk. More information on this release at: www.wellcome.ac.uk/News/Media-office/Press-releases/2010/WTX063297.htm 

ENDS

Press Office Contacts

Craig Brierley

Senior Media Officer, The Wellcome Trust, 215 Euston Road, London, NW1 2BE, U.K

T:+44 (0) 20 7611 7329, Email: c [dot] brierleywellcome [dot] ac [dot] uk

Pete Wilton

Press Officer, Mathematical, Physical and Life Sciences and Spin-Outs, University of Oxford

T+44 (0)1865 283877, Email: pete [dot] wiltonadmin [dot] ox [dot] ac [dot] uk

Justa Wawira

Head of External Relations, KEMRI-Wellcome Trust Research Programme

T:+254-41-7525603, Email: JWawirakilifi [dot] kemri-wellcome [dot] org

Author contacts for commentary

Dr Simon Hay: simon [dot] hayzoo [dot] ox [dot] ac [dot] uk (Tel: +44 (0) 1865 271243)

Dr Fred Piel: fred [dot] pielzoo [dot] ox [dot] ac [dot] uk (Tel: +44 (0) 1865 281210)

Suggested impartial contacts for commentary

Dr Kevin Baird

Eijkman-Oxford Clinical Research Unit, Jakarta, Indonesia

jkevinbairdyahoo [dot] com

Prof. Peter Zimmerman

Case Western Reserve University, Cleveland, OH, U.S

pazcase [dot] edu

Prof. Graham Serjeant

Medical Research Council Laboratories, University of the West Indies, Jamaica

grserjeantcwjamaica [dot] com

Notes for editors

1. Piel, F.B., A.P., Howes, R.E., Nyangiri O.A., Gething, P.W., Williams, T.N., Weatherall, D.J. and Hay, S.I (2010) Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis. Nature Communications. 2 Nov 2010. 1:104 doi: 10.1038/ncomms 1104

2. The Malaria Atlas Project (MAP) is funded by the Wellcome Trust (UK) to assemble medical intelligence and survey data to provide evidence-based maps on the distribution of malaria risk, human population, disease burdens, mosquito vectors, inherited blood disorders and malaria financing and control world wide. The maps generated are the results of a collaboration between malaria scientists in the UK, Kenya, Vietnam, Indonesia, Ecuador and the USA. MAP work in the Asia-Pacific region has been additionally supported by grants from the Li Ka Shing Foundation. For further information visit www.map.ox.ac.uk

3. The Wellcome Trust is a global charitable foundation dedicated to achieving extra ordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. www.wellcome.ac.uk

4. The Department of Zoology, within the Mathematical, Physical and Life Sciences Division at the University of Oxford, has a long-standing reputation for world class research and teaching. Research in the Department is organised into several research themes; these span a broad spectrum of biology ranging from ecology and behaviour, through to molecular evolution, development and infectious disease biology. www.zoo.ox.ac.uk

5. The Kenya Medical Research Institute (KEMRI) is a Kenya government parastatal with the responsibility for health research to improve the health of Kenyans. It is one of the most well developed national research institutes in Africa with a network of centres across Kenya such as the Centre for Geographic Medicine Research-Coast (CGMR-C), which is home to the KEMRI-Wellcome Trust Research Programme. The programme was formally established in 1989 as a partnership between KEMRI, Oxford University and the Wellcome Trust. It conducts basic, epidemiological and clinical research in parallel, with results feeding directly into local and international health policy. The programme aims to expand the country's capacity to conduct multidisciplinary research that is strong, sustainable and internationally competitive. www.kemri-wellcome.org

6. The Weatherall Institute of Molecular Medicine (WIMM) fosters research in molecular and cell biology with direct application to the study of human disease. Housing around 400 scientists, WIMM is proud to be at the forefront of an exciting research field impacting on the understanding and treatment of diseases ranging from Cancer to AIDS. The Institute was founded by Professor David Weatherall in 1989. The three main sponsors of research in the institute are the University of Oxford, The Medical Research Council and Cancer Research UK. Significant funding also comes from the Wellcome Trust and other medical research charities. www. imm.ox.ac.uk

7. The Philippe Wiener-Maurice Anspach Foundation aims to promote cultural relations between the Universite Libre de Bruxelles (ULB) (Free University of Brussels) and the Universities of Oxford and Cambridge. Since 1969 it has offered awards each year to students and postdoctoral researchers from Brussels to Oxford and Cambridge, and vice-versa. www.ulb.ac.be/iee/fwa