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One Size Doesn't Fit All

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Much of the discussion when it comes to personalized medicine centers on accurately interpreting individual genomes. But the genome is a bit of a moving target — and the evidence for this is written all over the human body.

"I used to have a full head of hair on my head. However, as I get older, I continue to lose my hair — I don't fully understand why, but one possibility is that the genome structure on my head is changing and those changes are contributing to the phenotype of my forehead," says Kiho Cho, an associate professor at Shriners Hospitals for Children, Northern California, and the University of California, Davis. "This concept applies to disease phenotypes as well. If you look at children, we don't see a lot of cancer patients. However, as we get older, we see more instances of cancer."

Cho and his colleagues decided to explore this concept by studying structural changes in the genome as they relate to age and organ tissue in association with the transposon activity of retroelements.

As Cho and his team reported in an April Experimental and Molecular Pathology article, the size of -genomes isolated from mouse liver tissues increased with age, peaking at five weeks. They found that the copy number of several retro-element sub-families were up to two-fold higher in liver tissue than in lung or spleen tissue. That an individual's genome structure is variable depending on age and organ type in association with the transposition of retro-elements may have broad implications for understanding biological phenomena, they said in the article.

"DNA is changing spatially and temporally, meaning that within one subject — in this case an inbred mouse — depending on the tissue type, the structure of DNA is different," Cho says. "And also, depending on the age, within the same tissue type, the DNA structure is changing. It is likely that DNA structure is unique for the individual cell, although we don't yet have as much data on that as we would like at this point."

Because the data from this study indicate that there may be multiple variant isoforms of an individual's genome, Cho says that personalized medicine is going to be more of a challenge to realize than was previously thought. A new protocol or system — and more research — will be needed to analyze and make sense of how the structural changes in the genome relate to an individual's health, he says.

"Based on my understanding of current scientific literature, I do not see people reporting these levels of changes in the -genome. But there is a genuine link between the findings of our research and the personal genome — for personalized medicine, we cannot just say that you have just one genome; it cannot just represent you or me," he says. "So there's a big question about how we define someone's personal genome. I don't have [an] answer for that, but I would say that we should be looking into each aspect of genome biology and incorporating the idea that genomes can be different depending on when and from what tissue you get the sample."

Cho's team would like to expand its work to investigate whether changes in the structure of the genome are cell type-specific, and try to answer questions about how some disease processes — tumorigenesis in particular — are linked to specific structural changes in the genome. Being able to pinpoint which structural changes in the genome correlate to a particular disease process might eventually provide clinicians with new prognostic markers, he says.

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