Advertisement
Sino Biological
Sino Biological

DNA may differ between tissues

Recent findings may spell trouble for genome-wide association studies based on DNA obtained through blood samples.

By | July 20, 2009

Genetic material may vary between blood cells and other tissues in a single individual, a study in the July issue of Human Mutation reports.

Image: Wikimedia

The study "raises a very interesting question," Howard Edenberg, director of the Indiana University School of Medicine's center for medical genomics, told The Scientist. Many genome-wide association studies—especially studies on systemic diseases such as diabetes and atherosclerosis—depend solely upon DNA harvested from blood samples to identify genes associated with medical conditions. But this study "suggests that looking only at blood, you may miss some things."

Searching for the genes behind a fatal condition called abdominal aortic aneurysm (AAA), researchers from McGill University in Montreal found that complementary DNA from diseased abdominal aortic tissue did not match genomic DNA from leukocytes in blood from the same patient. "We did not expect to find a difference in the tissue [genes] compared to the leukocyte [genes]," said endocrinologist Morris Schweitzer, who led the study. Schweitzer and his team uncovered three single nucleotide polymorphisms (SNPs) in samples of diseased tissue from 31 AAA patients that were not present in matching blood samples. They also tested five aortic and blood samples from normal individuals and found the same discrepancy.

Schweitzer said that the apparent genetic difference between different cells in the body may cast some doubt on genome-wide association studies that only use DNA from blood samples to infer disease states. "I think they may not be accurate because they might not reflect what's in the tissue," he said, adding that researchers should look upon such genetic results "very carefully and very trepidatiously."

Edenberg, who was not involved with the study but who conducts genome-wide association studies to explore the genetic roots of alcoholism and bipolar disorder, said that while the findings are interesting, they are very preliminary. "If they're correct about this, and there are these genomic differences between tissues and blood at certain alleles, then we're missing some things," he said. Edenberg explained that experimenters generally take into account that such studies are somewhat "underpowered" in terms of their ability to catch every genetic indicator of disease. Schweitzer's results, he noted, may add another layer to this consideration, but do not suggest that genome-wide association studies would turn up false positives, or blood-based genes mistakenly attributed to a particular disease.

Sudha Seshadri, a Boston University neurologist who was not involved in the study, told The Scientist that though the McGill group's results are important, they do not negate genome-wide association data that scientists have already gathered. "I don't think [the study] says much about the usefulness or validity of genome-wide association studies as they are being done in cohorts around the world." Genome-wide studies on diabetes, for example, have identified about 16 genes that are related (in varying degrees) to the disease, said Seshadri, who collaborates on the Framingham Heart Study, a six-decade longitudinal study on more than 5,000 people that has more recently included genomic data. "I think I would have suggested a few more experiments, personally," Edenberg added. In particular, he pointed to the fact that the McGill researchers were comparing complementary DNA from aortic tissue to genomic DNA from blood. "At the moment," he said, the discrepancy "seems relatively compatible with RNA editing [rather] than with a genomic issue." The study should have compared genomic DNA from the aortic tissues with the genomic blood DNA, and cDNA from both cell types, Edenberg said.

Schweitzer said his group is currently working on this experiment and "should have results probably in a couple of weeks." He noted that differences between tissue and blood DNA may account for the relatively low levels of association turned up by most genome-wide association studies. Of all the genome-wide association studies that have been conducted, he said, "No one has really found that one miracle gene that really points to something." Seshadri, however, said it's hasty to dismiss the value of such studies. "I think [the authors] make some provocative statements that express a viewpoint, but not a widely-accepted viewpoint," she said. "It's far too early in the process of genome-wide association studies to conclude that they have not been fruitful."

Advertisement

Comments

Avatar of: Horace Gaims

Horace Gaims

Posts: 4

July 20, 2009

My layman's question? Can this discovery of different DNA contents within one human body pose potential problems for criminal prosecutions based on DNA evidence?
Avatar of: anonymous poster

anonymous poster

Posts: 51

July 20, 2009

This finding is an eye opener in post-genomic era and points to the need for further research. It has apparently important implications for biomedical research and particularly genetic-related diseases.
Avatar of: anonymous poster

anonymous poster

Posts: 3

July 20, 2009

Hmmm....reviewers of my grants have raised this as a problem for over 10 years. So, maybe new "support" but the idea is not new.
Avatar of: anonymous poster

anonymous poster

Posts: 26

July 20, 2009

Do some biologists *not* know that B-cells and T-cells specifically reorganize their own genomes to produce diverse receptors / antibodies? Afterall, there was a Nobel prize given for this discovery... There are no cells in the body less likely to be genetically "pure" than white blood cells (and red cells jettison their nuclei altogether). So, obviously a different, non-lymphoid, tissue should be used for DNA samples when genomics are involved.\n\nBaxter Zappa
Avatar of: anonymous poster

anonymous poster

Posts: 107

July 20, 2009

Kudos for Howard Edenberg, and for Bob Grant. Inclusion of Edenberg's cautionary remarks earns this story its fifth star. A pity Edenberg did not referee the original paper before publication.
Avatar of: anonymous poster

anonymous poster

Posts: 85

July 21, 2009

Thank you, author of "This is surprising?/by anonymous poster," for remembering that the immune system is what it is as a result of the generation of genetic variability. Ever since the discovery of this genetic system, it has seemed obvious to me that it is highly unlikely that the immune system would be the only developmental / differentiation system that works via generation of genetic diversity. Rather, it seemed most likely to me that many (if not all) complex irreversible differentiation processes in multicellular organisms would utilize a similar type of genetic mechanism. PLUS, there is always the possibility of random somatic mutation in cellular lineages within a multicellular organism. So even comparing genomic DNA from buccal swabs with liver biopsy material should result in the discovery of at least some differences, for one reason or another (or multiple reasons). \n\nI certainly hope that this observation proves to not merely be a reflection of post-translational modifications (i.e., cDNA vs. genomic DNA), but rather a genuine difference in genomic sequences. Then perhaps the current paradigm to which most molecular biologists are unconsciously wedded will be revealed as a bubble in need of bursting in order to advance the field of developmental genetics.
Avatar of: Jeremy Wickins

Jeremy Wickins

Posts: 9

July 21, 2009

As an academic lawyer involved in biotechnology, including the use of DNA for identification purposes, I find this very interesting. I look forward to the report(s) on the further experiments being carried out. Well done to "The Scientist" for picking this up.
Avatar of: anonymous poster

anonymous poster

Posts: 1

July 22, 2009

human nature is very complex and no one knows for sure everything related to our body system.so i say their findings,though prelimenary,too important to neglect!
Avatar of: anonymous poster

anonymous poster

Posts: 28

July 22, 2009

"Then perhaps the current paradigm to which most molecular biologists are unconsciously wedded will be revealed as a bubble in need of bursting in order to advance the field of developmental genetics".\n\n"Personal medicine" beased genomic signature has been generaing a bubble for clinical diagnosis, prognosis and therapeutics. \n\nSomatic mutation seems a general law for developmental genetics. It is not suprising there is a difference of genome between tissue cells, even between cells within the same tissue. Diseased cells are more susceptible to mutation than healthy cells, especially in cancers. Examining blood cells without looking at diseased tissue cells will give rise to either false negative or fals positive.\n\n\n
Avatar of: ROULETTE Wm. SMITH

ROULETTE Wm. SMITH

Posts: 10

August 2, 2009

In a 1979 report, I cited and reported considerable evidence that DNA must be repositories of long-term memories in living systems (LTM) - all claims to the contrary notwithstanding. That report accurately anticipated 'immune dementia' (e.g., GRIDS/HIV/AIDS et al.) based on studies of lentiviruses and other 'slow' viruses. The McClintock and Tonegawa findings represented a very small part of that evidence. Perhaps more important, the central dogma was cited as the principal impediment limiting one's ability to think outside-the-box. I then conceptualized, designed and invented a 'preliophic moleculator' (i.e., a PRotonic-ELectronic-IOnic-PHotonIC MOLECUlar calcuLATOR) device and processes (patents pending) to specifically prove the concept and expand upon the notion of using electromotive forces to propel molecules in vectorized processes (i.e., beyond electrophoresis). My findings suggest that DNA in the immune system, brain, developmental tissue and other repositories of LTM are likely to differ systematically. A central challenge is to disambiguate the underlying 'code(s)'. In brain, a second challenge is to identify 'a priori' molecular events giving rise to 'a posteriori' neural networks.

Follow The Scientist

icon-facebook icon-linkedin icon-twitter icon-vimeo icon-youtube
Advertisement

Stay Connected with The Scientist

  • icon-facebook The Scientist Magazine
  • icon-facebook The Scientist Careers
  • icon-facebook Neuroscience Research Techniques
  • icon-facebook Genetic Research Techniques
  • icon-facebook Cell Culture Techniques
  • icon-facebook Microbiology and Immunology
  • icon-facebook Cancer Research and Technology
  • icon-facebook Stem Cell and Regenerative Science
Advertisement
Advertisement
Life Technologies