Monday, July 23, 2007

The genetics of HIV infection   posted by p-ter @ 7/23/2007 08:16:00 PM

AIDS is obviously not a genetic disease-- if one were to make a list of risk factors predisposing to HIV infection, genetics would be a pretty low-ranking member (though still present on the list, of course). Yet genetics is still a useful tool for understanding the disease, as evidenced by this paper:
Understanding why some people establish and maintain effective control of HIV-1 and others do not is a priority in the effort to develop new treatments for HIV/AIDS. Using a whole-genome association strategy we identified polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set point period of infection. One of these is found within an endogenous retroviral element and is associated with major histocompatibility allele HLA-B*5701, while a second is located near the HLA-C gene. An additional analysis of the time to HIV disease progression implicated a third locus encoding a RNA polymerase subunit. These findings emphasize the importance of studying human genetic variation as a guide to combating infectious agents.
People trained to think about disease from a "public health" (read: short-term) standpoint might be a little appalled by the amount of money spent on a study like this-- those hundreds of thousands of dollars could very well have been spent on far more effective ways to reduce AIDS prevalence.

However, the goal here is more long-term-- understanding the variation in how humans interact with pathogens will lead to more effective drug targeting and greater understanding of immunity down the road. Genome-wide association studies also, given the fact that they are largely hypothesis-free, also provide a way to generate novel hypotheses (or confirm old ones) about disease aetiology. In this study, for example, one of the major signals lies in an endogenous retrovirus-- that is, a virus that has incorporated itself into the genome. This raises the intriguing possibility that some of our immune response is mediated by viruses that previously spliced themselves into the genome (the authors mention that antisense transcripts would be a very plausible mechanism by which that could work).

The genetics of any phenotype you can think of will eventually be mapped, and this information will be useful not necessarily for its predictive value (though in some cases that will be the case), but also for the basic understanding of the phenotype that it carries with it. This site sometimes sees speculation as to the causes of variation in sexual orientation, for example-- genetic studies (assuming they're carried out) will severely restrict the plausible "hypothesis space" on that question.

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