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Pro-Test: standing up for science
Pro-Test: Standing Up For Science
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17/04/07

Permalink 10:52:38 am, by Tom, 575 words, 2714 views   English (UK)
Categories: Information

Publication of the Macaque Genome

The latest issue of Science (http://www.sciencemag.org) included another milestone in medical research, the publication of the draft Genome sequence of Macaca Mulatta, the rhesus macaque(1). The rhesus macaque has made a huge contribution to medical progress, from the identification of the Rhesus factor by Karl Landsteiner and Alexander Wiener in 1937 to recent breakthroughs in the treatment of Parkinson's disease (http://www.pro-test.org.uk/facts.php?lt=aa), though it's probably best known for its essential role in ongoing efforts to develop a vaccine against HIV (http://www.iavi.org/).

The simian immunodeficiency virus (SIV) infected macaque is the most useful model for evaluation of new HIV vaccination strategies(2). It's also been crucial to our understanding of HIV pathology, for example in 1998 Ronald Veazey and Andrew Lackner demonstrated that rapid depletion of CD4+ T cells occurred in the gut of SIV infected macaques. Their discovery was later confirmed in HIV infected humans, and indicates that a successful HIV vaccine will need to protect against mucosal tissue infection(3).

Analysis of how the genetic similarities and differences between the macaque and human, and indeed between macaque populations, relate to differences in susceptibility to disease will enable the identification of more protective factors such as TRIM5α, which protects the rhesus macaque from HIV(4). These discoveries may facilitate development of potent new approaches to the prevention and treatment of HIV infection.

Publication of high quality sequences for over 20,000 macaque genes will for the first time allow scientists to build microarrays to simultaneously study the expression of thousands of individual genes in the macaque, an approach which has already lead to valuable insight into the role of the host immune response in the pathology of the 1918 influenza5, and to identify the genes in macaque which correspond to those that are faulty in human diseases such as cystic fibrosis.

Perhaps most importantly comprehensive knowledge of the components of the immune and other systems in the rhesus macaque will enable scientists to design better experiments and have greater confidence in how well the results correspond to human disease. In doing so it will enhance the usefulness of the rhesus macaque in HIV vaccine research, by highlighting the vaccine strategies that are more likely to succeed in human trials.

We don't know if the availability of the draft genome will lead to an increase in the number of rhesus macaques used in medical research, through better experimental design and by aiding the development of transgenic rodents to replace macaques it may even lead to a reduction in their use. What is clear is that the draft genome of Macaca Mulatta is a tremendous resource, not only for those studying primate evolution but also for scientists working to cure some of the world's most dreaded diseases.

Paul Browne

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References

1. Gibbs R.A. et al. "Evolutionary and Biomedical Insights from the Rhesus Macaque Genome." Science Vol. 316, pages 222-234 (2007).

2. Girard M.P. et al. "A review of vaccine research and development: the human immunodeficiency virus (HIV)." Vaccine Vol. 24, pages 4062-4081 (2006).

3. Veazey R.S. and Lackner A.A "Getting to the guts of HIV pathogenesis." Journal of Experimental Medicine Vol. 200, pages 697-700 (2004).

4. Stremlau M. et al. " The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys." Nature Vol. 427, pages 848-853 (2004).

5. Bass T. et al. " Integrated molecular signature of disease: analysis of influenza virus-infected macaques through functional genomics and proteomics." Journal of Virology Vol. 80, pages 10813-10828 (2006).

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