Major Genetic Differences between Blood and Tissue Cells

dna splitGenome-wide association studies aim to identify genetic contributions to common diseases such as diabetes and atherosclerosis by comparing samples from those with the disease and healthy individuals. Because of the difficulty in sampling diseased tissue from living patients, blood samples are often used for the comparisons. The impact of such studies is potentially substantial, but scientists at McGill University have now sounded a note of caution about the use of blood samples as surrogates.

It had been assumed that DNA is essentially identical in every cell in the body, and that blood acts as a good surrogate for other tissues but, in an investigation into the underlying genetic causes of abdominal aortic aneurysms (AAA), the McGill team found differences between DNA from blood samples and diseased tissue. AAA is a localised widening and weakening of the abdominal aorta which can lead to fatal rupture of the aorta and is one of a small number of vascular diseases in which tissue samples are removed as part of therapy. Since activation of apoptosis has been linked to the development and progression of AAA, the team were examining the role of sequence variations in the BAK1 gene (BAK1) which encodes a pro-apoptotic protein. BAK1 abdominal aorta cDNA from AAA patients and healthy individuals were compared with each other as well as with BAK1 genomic sequences obtained from matching blood samples. Specific BAK1 single nucleotide polymorphism (SNP) containing alleles were found in both aneurysmic (31 cases) and healthy aortic tissue (5 cases) but not in the matching blood samples. If the mutations discovered in the tissue cells are found to predispose for AAA – or other vascular diseases – they could lead to new therapeutic targets. Although the study compared complementary DNA from aortic tissue with genomic DNA from blood, if the mismatch between blood and tissue samples turns out to be a general phenomenon when comparing like DNA, it questions the validity of the widespread practice of using blood samples to represent diseased tissue in genome-wide association studies.

The study is published in full in the July issue of the journal Human Mutation.