The initial ENCODE report was interesting enough to encourage the U.S. based National Human Genome Research Institute to fund a study of the whole human genome. As a result, in 2012, a new larger ENCODE consortium published its results. In summary they found that:
The vast desert regions have now been populated with hundreds of thousands of features that contribute to gene regulation. And every cell type uses different combinations and permutations of these features to generate its unique biology.
.....the person who became best known for his attacks on ENCODE was Dan Graur. Concerning the 80% functional claim of the consortium for the human genome, Dan Graur and colleagues declared:
Progress in understanding the functional significance of DNA sequences can only be achieved by not ignoring evolutionary principles.
As an alternative, Graur and his friends argued for a 10% functional proportion in the genome.Their article was provocatively entitled: “On the immortality of television sets: ‘Function’ in the human genome according to the evolution-free gospel of ENCODE.”
.....in their reply, however, the ENCODE II consortium referred to another bombshell connected to their report: the fact that since 2005, important genetic markers connected with specific diseases, had increasingly been identified in the noncoding part of the genome (that is, the part not connected with genes, supposedly representing junk DNA). The consortium used Genome Wide Association Studies (GWAS) in part to make these identifications. Meanwhile, progress in the ability to obtain sequences of entire genomes from more and more people developed. Specialists began to look for unique markers in people with a specific disease (or condition) compared to others who lacked this trait. And surprise, surprise:
More recently, genome-wide association studies have indicated that a majority of trait-associated loci [locations], including ones that contribute to human diseases and susceptibility, also lie outside the protein-coding regions. These findings suggest that the noncoding regions of the human genome harbor a rich array of functionally significant elements with diverse regulatory and other functions.”
The scientists had discovered that a great deal of important activity was going on in noncoding regions of the genome. If markers of disease are found not connected to genes, it must mean that something important is going on in these noncoding regions. If the area were unimportant, a change in the DNA order of nucleotides there would not matter one way or the other. But it obviously did matter.