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

Abstract

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 ∼ 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. © 2009 Landes Bioscience.