Complexity of a small non-protein coding sequence in chromosomal region 22q11.2: presence of specialized DNA secondary structures and RNA exon/intron motifs

Nicholas Delihas

DiGeorge Syndrome is a genetic abnormality involving ~3 Mb deletion in human chromosome 22, termed 22q.11.2. To better understand the non-coding regions of 22q.11.2, a small 10,000 bp non-protein-coding sequence close to the DiGeorge Critical Region 6 gene (DGCR6) was chosen for analysis and functional entities as the homologous sequence in the chimpanzee genome could be aligned and used for comparisons. The GenBank database provided genomic sequences. In silico computer programs were used to find homologous DNA sequences in human and chimpanzee genomes, generate random sequences, determine DNA sequence alignments, sequence comparisons and nucleotide repeat copies, and to predicted DNA secondary structures. At its 5' half, the 10,000 bp sequence has three distinct sections that represent phylogenetically variable sequences. These Variable Regions contain biased mutations with a very high A + T content, multiple copies of the motif TATAATATA and sequences that fold into long A:T-base-paired stem loops. The 3' half of the 10,000 bp unit, highly conserved between human and chimpanzee, has sequences representing exons of lncRNA genes and segments of introns of protein genes. Central to the 10,000 bp unit are the multiple copies of a sequence that originates from the flanking 5' end of the translocation breakpoint Type A sequence. This breakpoint flanking sequence carries the exon and intron motifs. The breakpoint Type A sequence seems to be a major player in the proliferation of these RNA motifs, as well as the proliferation of Variable Regions in the 10,000 bp segment and other regions within 22q.11.2. The data indicate that a non-coding region of the chromosome may be reserved for highly biased mutations that lead to formation of specialized sequences and DNA secondary structures. On the other hand, the highly conserved nucleotide sequence of the non-coding region may form storage sites for RNA motifs.