In a letter to Nature, Mark Ptashne, Oliver Hobert, and Eric Davidson question an editorial that appeared in the journal (Nature).

The editorial, focused on the International Human Epigenome Consortium, and says that it is “clear that epigenetics … could explain much about how similar genetic codes are expressed uniquely in different cells, in different environmental conditions and at different times.”

However, Ptashne, Hobert, and Davidson say that epigenetic marks stem from the DNA sequence and its interations with RNA and proteins. “They are thus directly dependent on the genomic sequence,” they write.

At Adaptive Complexity, Michael White says he agrees with Ptashne, Hobert, and Davidson.
The idea that genomes between species are too similar to account for species diversity is absolute nonsense. And "so is the idea that epigenetic information is completely independent of DNA sequence,” he writes.

This writer is of the opinion that it is clear that we have much more to learn about the role of epigenetics in DNA modification and biological processes underlying the mechanisms leading to human disease.

Ptashne points out as early as 2007 (On the use of the word 'epigenetic', Curr Biol. 2007 Apr 3;17(7):R233-6) that "there is much excess baggage that comes with misuse of this term [epigenetics] that can have misleading implications."

It is my opinion that Ptashne is on the mark, and also, that many people confuse the word "epigenetics" with "epigenomics", which is far more inclusive. It is unfortunate that these terms are used loosely, potentially causing misleading thoughts about the classification of mechanisms that might change gene expression and consequently cell function or evolution.

    Impact of the HGP on Medicine

More recently in the journal Nature (Nature 470, pp 187–197, 10 February 2011), Dr. Eric Lander assesses the "Initial impact of the sequencing of the human genome and asserts that "genomics has provided the first systematic approaches to discover the genes and cellular pathways underlying disease."

    Genetic Basis for Human Disease

This has far reaching consequences for the future practice of medicine because whereas candidate gene studies have yielded slow progress, comprehensive approaches aided by the identification of genomic sequence data has exposed ~2,850 genes underlying rare Mendelian diseases, ~1,100 loci affecting common polygenic disorders and ~150 new recurrent targets of somatic mutation in cancer.

These discoveries are propelling research throughout medicine, academia and industry.

    Early Surprises

One could argue that the most surprising discovery made in the first ten years after the publication of the first human sequence is that majority of the sequences coding for functional molecular entities do not code for proteins. These features had been missed by decades of molecular biology, because scientists had no clue where to look. In fact, protein-coding sequences comprise only ~1.5% of the genome and are dwarfed by functional conserved non-coding elements (CNEs).

Indeed, one early application of massively parallel genomic sequencing was to create ‘epigenomic maps’, showing the locations of specific DNA modifications, chromatin modifications and protein-binding events across the human genome that could potentially affect the phenotypic expression of native DNA sequences. (Definitions: Phenotype, Genotype).

    Future Surprises Ahead

In conclusion, our understanding of epigenetics and epigenomics has been undergoing rapid evolution in response to the systematic reshaping of our view of genome physiology. We can expect that much more will be revealed as we continue to make new and exciting discoveries about the roles of protein-coding genes, non-coding RNAs and regulatory sequences in determining human health and disease.

Food for thought - Ken Niebling