Animal Rights

Single Gene Multiple Functions

| by Dr Ray Greek

A study out of Yale has revealed that:

Mutations in a single gene can cause several types of developmental brain abnormalities that experts have traditionally considered different disorders. "This is going to change the way we approach single-gene disorders," said lead investigator Murat Gunel, MD.

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Gunel went on to say that a single gene "is required for strikingly diverse aspects of human cortical brain development." The study was published August 22 in Nature.

I have been blogging about why small differences in genetic composition can lead to dramatic differences in outcomes vis-à-vis drugs and disease. This is yet another example of why genetically altered mice have failed to predict human response. Genes in mice and humans do not share a one to one correspondence for complex traits like drug and disease response nor do single genes do single things. For example:

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One puzzling discovery is that several mutations that cause genetic diseases in humans - such as phenylketonuria and Sanfilippo syndrome, which lead to mental retardation - are the normal form in macaques and, presumably, our own ancestors. "How can genes that seem to be fine in one species give disease in another closely related one?" asks Richard Gibbs, a geneticist at Baylor College of Medicine in Houston, Texas, who led the consortium. It is in delicately balanced genes like these that we may find some of the key steps in the evolution of modern humans. Some cases of mental retardation, Gibbs speculates, may even result from mutations that restore a key gene to its ancestral condition. (Holmes 2007)

The Yale study was carried out in humans then reproduced in mice. So mice, not surprisingly, also have genes that are multifunctional. The point is not that mice and humans share traits—diverse functions of single genes—but rather that these very traits explain the different responses to drugs and disease. Society is interested in drug and disease response and so should health care researchers or researchers who obtain funding ostensibly for advancing health care.

When the above is combined with the facts that humans and animals are robust complex systems, that genes work in networks, and that genes are affected by modifier genes, it should come as no surprise that genetically altered animals have failed as predictive models for human response to drugs and disease. (See Animal Models in Light of Evolution for more.)

I should also point out that this new knowledge was by no means dependent upon mouse models. The exome wide association study that is reported in Nature is similar to genome wide association studies that have yielded so much information about human gene-disease links. Mice are not needed for these human-based studies.