Mapping the sequences of potential guanine quadruplex motifs

The knowledge that potential guanine quadruplex sequences (PQs) are non-randomly distributed in relation to genomic features is now well established. However, this is for a general potential quadruplex motif which is characterized by short runs of guanine separated by loop regions, regardless of the nature of the loop sequence. There have been no studies to date which map the distribution of PQs in terms of primary sequence or which categorize PQs. To this end, we have generated clusters of PQ sequence groups of various sizes and various degrees of similarity for the non-template strand of introns in the human genome. We started with 86 697 sequences, and successively merged them into groups based on sequence similarity, carrying out 66 clustering cycles before convergence. We have demonstrated here that by using complete linkage hierarchical agglomerative clustering such PQ sequence categorization can be achieved. Our results give an insight into sequence diversity and categories of PQ sequences which occur in human intronic regions. We also highlight a number of clusters for which interesting relationships among their members were immediately evident and other clusters whose members seem unrelated, illustrating, we believe, a distinct role for different sequence types.