ZHuntIII: A Computer Approach To Mapping Z-DNA Within Human Chromosomes 21 and 22

Speaker: Christoph Champ

Abstract: In this project (ZHuntIII), we have developed several processes and programs in order to map the potential Z-DNA-forming sequences within the recently sequenced human chromosomes 21 and 22. The seven programs developed (collectively called ZHuntIII) employ rigorous thermodynamic search strategies, statistical mechanics, and pattern matching and comparison. ZHuntIII has been built upon past research, biochemical and biophysical principles, and computational techniques. The ZHuntIII search algorithm considers sequence type, length, and cooperativity to determine a “Z-Score” for a specified stretch of potential Z-DNA-forming nucleotides. The higher a Z-Score, the more likely that sequence is to adopt the Z conformation. Since every base pair within the chromosomes is assigned a Z-Score, we must choose only those Z-Scores that represent the highest likelihood in forming potential Z-DNA-forming sequences. In genomic sequences, these Z-Scores have been found to have values covering seven orders of magnitude. When plotting these values on a graph, the highest Z-Scores are easily visible as relatively few peaks raising several orders of magnitude among the majority of lower Z-Scores. We have chosen a threshold that is in the same order of magnitude as there are genes within human chromosomes 21 and 22. We expect this determination to compliment past research which has shown potential Z-DNA-forming sequences to occur upstream of the first expressed exon in a gene. That is, they are most commonly found near the 5’ end of genes. We hope to show that this is also the case with most genes in much larger sequences, as those of human chromosomes 21 and 22.