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| Scientists aim to identify genes that were not previously implicated in human disease with the Human Knockout Project. Courtesy: http://www.dermamedics.com/science_id35.html |
When scientists aim to uncover the function of a gene, where do they start? They know that genes make up the chromosomes that occupy the nucleus of every cell, but how can this feat be achieved? The classical method for elucidating a gene's function is by "knocking out," or eliminating, the function of the gene. Scientists can prevent a gene from being expressed by introducing mutations, or changes to the genetic sequence, in the gene of interest. They can also introduce a foreign gene into the gene's chromosomal location to prevent it from being converted into messenger RNA, which would in turn prevent protein production. These knockout experiments have been performed in several organisms such as worms, yeast, flies, and mice, and initiatives such as the Knockout Mouse Project (KOMP) venture to collect information detailing the physical effects that result from the ablation of individual genes.
Due to ethical issues, these initiatives were not implemented in humans. However, Dr. Daniel McArthur at Harvard University has circumvented this roadblock. He is deeply intrigued in the existence of healthy "human knockouts," people that lack function of individual genes without illness, so he began the Human Knockout Project. This endeavor involves the study of naturally occurring mutations in humans that result in the loss of genetic function. This allows Dr. McArthur's group to avoid many of the ethical issues that surround human genetic research. Dr. McArthur stresses that in addition to the necessity for understanding the effects of genetic mutations in essential genes, it is as important to study mutations in genes that lack deleterious effects. This knowledge could lead to the elucidation of genes that are known to improve responses to cancer treatment, for example, and methods to decrease or eliminate the function of these genes can be pursued in humans.
The Human Knockout Project is a creative way to address the relevance of individual genes to human disease. Oftentimes, scientists tend to have a linear methodology for studying the role of genes in disease, usually focusing on genes that confer harmful effects upon elimination. But as Dr. McArthur eloquently described, we forget that the loss of a subset of genes can bestow beneficial effects on an organism, and ultimately this may revolutionize the current mode of thinking when treating disorders such as Alzheimer's and diabetes. With the implementation of the Human Knockout Project, it is possible that additional efforts to understand the function of human genes can be formulated and carried out in an ethical manner.
