Contrary to popular belief, body cells in a human may not all have the same DNA

According to an article in Science Daily, 15 July 2009, "research by a group of Montreal scientists calls into question one of the most basic assumptions of human genetics: that when it comes to DNA, every cell in the body is essentially identical to every other cell."
The original report of the results appears in the July issue of the journal Human Mutation.
The article continues:

This discovery may undercut the rationale behind numerous large-scale genetic studies conducted over the last 15 years, studies which were supposed to isolate the causes of scores of human diseases.

Most body samples used in large-scale genomic studies are saliva or blood. If these samples have DNA that doesn't match genetically to cells in the diseased or affected tissue--which this report suggests is likely--then, the samples may not tell us "the truth" about the DNA makeup responsible for the disease being investigated. Thus, "ambitious and expensive genome-wide association studies may prove to have been essentially flawed from the outset."

The article continues:

This discovery sprang from an investigation into the underlying genetic causes of abdominal aortic aneurysms (AAA) led by Dr. Morris Schweitzer, Dr. Bruce Gottlieb, Dr. Lorraine Chalifour and colleagues at McGill University and the affiliated Lady Davis Institute for Medical Research at Montreal's Jewish General Hospital. The researchers focused on BAK, a gene that controls cell death.

What they found surprised them.

AAA is one of the rare vascular diseases where tissue samples are removed as part of patient therapy. AAA is a localized widening and weakening of the abdominal aorta, and affects primarily elderly Caucasian men who smoke, have high blood pressure, and high cholesterol levels. It often has no symptoms, but can lead to aortic ruptures which are fatal in 90 per cent of cases.

When researchers compared BAK genes in blood cells and tissue cells coming from the same individuals, they discovered major differences. The suspected disease "trigger" was found only in the affected tissue. The same differences were later evident in samples derived from healthy individuals.

So, what are the implications of these results? According to Gottlieb, a geneticist with McGill's Centre for Translational Research in Cancer,

We can only look at the blood cells of patients with multi-factorial diseases other than cancer. Traditionally when we have looked for genetic risk factors for, say, heart disease, we have assumed that the blood will tell us what's happening in the tissue. It now seems this is simply not the case.

From a genetic perspective, therapeutic implications aside, the observation that not all cells are the same is extremely important. Genome-wide association studies were introduced with enormous hype several years ago, and people expected tremendous breakthroughs. They were going to draw blood samples from thousands or hundreds of thousands of individuals, and find the genes responsible for disease.

Unfortunately, the reality of these studies has been very disappointing, and our discovery certainly could explain at least one of the reasons why.

I have not had a chance to check this report out in other sources, but will when I can--I'm traveling tomorrow.

Marie Godfrey, PhD

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