Archive for August, 2006


3 Chromosomes Mapped Epigenetically

August 15, 2006

The Human Epigenome Project Consortium, a public/private collaboration led by Epigenomics AG and the Wellcome Trust Sanger Institute have published comprehensive epigenetic data for chromosomes 6, 20, and 22. The group, founded in 2003, hopes to identify and catalog all Methylation Variable Positions (MVPs) in the human genome.

The group is excited about their progress with the Human Epigenome Project:

“This is the first study report ever establishing the DNA methylation blueprint for whole chromosomes,” said Alexander Olek, CEO of Epigenomics AG, “and we believe the results justify the effort. As an example, we found that between the specimens examined, a surprisingly high proportion of the genomic sites are differentially methylated. So science may have underestimated the role of DNA methylation in gene regulation and tissue differentiation. The data constitute an important reference tool for further epigenetic studies and will help us to identify new marker candidates for a variety of medical conditions.”

The results were patented, and Epigenomics intends to use the data for for development of diagnostic products. The data is expected to be particularly useful for research into cancer, mental health and aging. The next step is to use the MVPs as a reference for epidimilogical studies to find out how they correlate to health and disease states.

This is genuinely good news, but its not going to stop me from grumbling about the patents.


Nucleosome Code

August 5, 2006

Scientists claim to have discovered an epigenetic code. This could be a fundamental discovery in the field. This weeks New York Times Science Section has a very accessible explanation.

Researchers believe they have found a second code in DNA in addition to the genetic code.

The genetic code specifies all the proteins that a cell makes. The second code, superimposed on the first, sets the placement of the nucleosomes, miniature protein spools around which the DNA is looped. The spools both protect and control access to the DNA itself.Jerry Workman of the Stowers Institute in Kansas City said the detection of the nucleosome code was “a profound insight if true,” because it would explain many aspects of how the DNA is controlled.

In the genetic code, sets of three DNA units specify various kinds of amino acid, the units of proteins. A curious feature of the code is that it is redundant, meaning that a given amino acid can be defined by any of several different triplets. Biologists have long speculated that the redundancy may have been designed so as to coexist with some other kind of code, and this, Dr. Segal said, could be the nucleosome code.

This discovery is very early in the scientific process and needs to be verified. If it pans out, it could provide the basis for more powerful epigenetic epidimiology. I’ll keep tabs on this story as the implications become more clear.


False Starts in Psychiatric Genetics

August 2, 2006

You’ve probably seen the headline a dozen times “Researchers at State College University Discover the Gene for Depression”. And yet it seems like no progress has been made towards understanding the genetic basis for psychiatric diseases. How can this be?

Well the fundamental reason for the lack of progress is that psychiatric diseases, like most interesting genetic traits, are the result of complex interactions between a number of genes. Every study that gets talked about in the media is only a small part of a very complex puzzle. It will take many years of broader more detailed studies to start to uncover the patterns in which these genes interact to cause psychiatric disorders.

However the problem goes deeper than that. The entire search for genetic causes of psychiatric diseases is undermined by the vague and arbitrary nature of psychiatric diagnosis. Many people are shocked to find out that there is no ‘test’ for depression, schizophrenia or any other psychiatric disease. There are only generally accepted guidelines (found in DSM-IV – the current edition of the diagnostic and statistical manual). Human inconsistencies in assigning diagnoses make it extremely difficult to do statistical analysis across studies.

Even more problematic than inconsistency in assigning psychiatric diagnoses, is inconsistency in the diagnoses themselves. Psychiatric diseases are a poorly designed, fuzzy set. That means that patients often fit into the definitions of mulitiple diseases. This ambiguity is a consequence of diagnosis using external symptoms. Because every person is different, their disease manifests in different ways, making it very difficult to identify exactly what their pathology is. Ths suggests that the search for genetic causes to psychiatric diseases may never bear fruit.


Chronic disease and epigenetics

August 1, 2006

Physiological or Health capital has been a research interest of Nobel Laureate Economist Robert Fogel for nearly three decades. Now his research into historical trends in life expectancy and chronic disease is uncovering historical evidence for epigenetics. Today’s New York Times describes his findings in a very interesting and accessible article comparing us to our Civil-war era counterparts.

The most striking part of the article was the description of the chronic health problems suffered by Civil War-era Americans. The article tells the story of Valentin Keller, a tailor in the 1860s, who developed crippling (literally) arthritis and lung disease at 26, and died at 40. Keller’s modern day descendants are in their 50s and 60s without any hint of his health problems.

Genetically, we are nearly identical to our great-great-grandparents. The reason for our discrepancy in health outcomes is usually interpreted as the consequence of modern health care and quality of life.

This explanation does not capture the whole story. Not only do we live longer than our great-great grandparents, we are bigger, stronger, and healthier. We also age slower. Researchers who investigate these trends have found that even the people who survived their early illnesses were much more likely to be afflicted with health problems in their 50s. That a severe illness early in life accelerates aging, and increases the risk for diseases such as heart disease and cancer later in life. This finding reinforces what the <animal studies> have been telling us for years.

This description just screams Epigenetics to me. Environmental insults will have effect gene regulation and expression patterns, compounding health effects over time. This is fits perfectly with the study that showed that identical twins become more and more different epigenetically as they age. This article hints at epigenetics by referencing our favorite <winter famine> but says nothing of the second-generation effects, or epigenetics.

(A quick aside, the overwhelming message here is that people today are healthier by every barometer other than BMI than they were at any other time in history. Is the obesity epidemic an issue to be seriously dealth with – yes. Is it something that is threatening society as we know it – absolutley not. Rant Over)

The take home here is

  1. Be careful with your body – what you do to it now will effect you (and perhaps your children) and that health effects compound. It’s all related.
  2. More research emphasis is needed on the intersection between disease and long-term health. Epigenetically focused epidemiology would be incredibly valuable data.