Human genome connectivity code links disease-associated SNPs, microRNAs and pyknons.

Discovery of pyknons, the most frequent, variable-length DNA sequence motifs in the human genomes, suggests extensive sequence-based connectivity between non-coding and protein-coding components of human genomes. Here we report identification of ubiquitous template design sequences (templum intentio series, templints) of human genomes common for disease-associated SNPs, microRNAs and pyknons. We demonstrate that genome-unique SNP-coding sequences associated with multiple common human disorders appear assembled from series of ubiquitous short octamer sequences shared by 5'-UTR pyknons and microRNAs. Our analysis suggests that units of genetic information encoded in the linear sequences of the 3.6 billion bases of human genome are condensed in approximately 200,000 bases (0.006%) of 5' UTR pyknons which are represented by hundreds of copies in a genome and utilized to build genome-unique sequences. Allele-specific sequence variations link disease-associated SNPs to distinct sets of pyknons and microRNAs, suggesting that increased susceptibility to multiple common human disorders is associated with global alterations of genome-wide regulatory templates affecting the biogenesis and functions of non-coding RNAs.