Novel RNAs identified from an in-depth analysis of the transcriptome of human chromosomes 21 and 22

In this report, we have achieved a richer view of the transcriptome for Chromosomes 21 and 22 by using high-density oligonucleotide arrays on cytosolic poly(A)+ RNA. Conservatively, only 31.4 % of the observed transcribed nucleotides correspond to well-annotated genes, whereas an additional 4.8 % and 14.7 % correspond to mRNAs and ESTs, respectively. Approximately 85 % of the known exons were detected, and up to 21 % of known genes have only a single isoform based on exon-skipping alternative expression. Overall, the expression of the well-characterized exons falls predominately into two categories, uniquely or ubiquitously expressed with an identifiable proportion of antisense transcripts. The remaining observed transcription (49.0%) was outside of any known annotation. These novel transcripts appear to be more cell-line-specific and have lower and less variation in expression than the well-characterized genes. Novel transcripts were further characterized based on their distance to annotations, transcript size, coding capacity, and identification as antisense to intronic sequences. By RT-PCR, 126 novel transcripts were independently verified, resulting in a 65 % verification rate. These observations strongly support the argument for a re-evaluation of the total number of human genes and an alternative term for “gene ” to encompass these growing, novel classes of RNA transcripts in the human genome. [Supplemental material is available online at www.genome.org. All novel, sequence-verified transcripts (Supplemental Table S4) have been submitted to dbEST (CF798425–CF798506). The following individuals kindly provide