Archive for the ‘Epigenetics’ Category


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.


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.

Epigenetics Based Breast Cancer Test

June 21, 2006

In this month’s edition of Clinical Cancer Research, researchers report that they have developed a new diagnostic test for breast cancer. By using Quantitiatvie multiplex methylation-specific PCR (QM-MSP) of body fluid, they claim to be able to double the rate of detection of breast cancer.

Because this system is so non-invasive and inexpensive, women will be able to screen for breast cancer much more often – increasing the chances of early detection. As more epigenetic epidimiology studies are completed, tests like this will become even more comprehensive.

Cancer research has long been at the forefront of applied epigenetics. Changes links between cancer and changes in DNA methylation patterns are well established. I would like to see researchers of cardiovascular disease and other chronic illnesses adapt similar strategies.


Human Epigenome Project

January 15, 2006

The American Association of Cancer Researchers have published a blueprint for a comprehensive international Human Epigenome Project. According to the authors –

“The goal of the HEP (Human Epigenomic Project) is to identify all the chemical changes and relationships… that provide function to the DNA code, which will allow a fuller understanding of normal development, aging, abnormal gene control in cancer and other diseases, as well as the role of the environment in human health.”

The proposed structure involves a “low-resolution scan” of a large group of samples to get a general picture of the epigenome. And then focused, detailed mapping of a handful of high-interest ‘reference epigenomes’. The AARC wants the project to happen in conjunction with the existing European and Japanese efforts.

The researchers claim that the technology necessary for high-throughput mapping of the epigenome is within sight. The most promising approach involved –

“The so-called ChIP/chip methodology, in which intact chromatin – the complex of DNA and histones – is immunoprecipitated (brought out of solution using antibodies that recognize specific histone modifications) and analyzed on microarray “chips.” Modifications of DNA are also tracked on chips, following treatment with enzymes that recognize sites of methylation. Impressive accounts of success with these methods were presented at the workshop.”

I love this idea and hope that it gains momentum. The existing European effort hopes to have 10% of the human epigenome mapped by fall 2006. An international effort, with considerable American support, could move much much faster (to state the obvious). I agree with the statement in the report that, ultimately, the Human Epigenome Project could have a bigger impact than the Human Genome Project Especially in fields like psychiatry that have not benefitted from gene sequence based approaches.

I can see a few obstacles that might interfere with cooperation with the Europeans. As of now, Epigenomics AG, a German molecular diagnostics firm, stands to patent all of the MVPs identified by the Human Epigenome Project. During the Human Genome Project, the US Government was vehemently opposed to Celera’s patenting of genetic information. Assuming that the US government’s position hasn’t changed on this topic, it may be difficult to get public funding for a project involving the Europeans.