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Genome Res. 14:331-342, 2004
©2004 by Cold Spring Harbor Laboratory Press; ISSN 1088-9051/04 $5.00
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Novel RNAs Identified From an In-Depth Analysis of the Transcriptome of Human Chromosomes 21 and 22

Dione Kampa1, Jill Cheng, Philipp Kapranov, Mark Yamanaka, Shane Brubaker, Simon Cawley, Jorg Drenkow, Antonio Piccolboni, Stefan Bekiranov, Gregg Helt, Hari Tammana and Thomas R. Gingeras

Affymetrix, Santa Clara, California 95051, USA

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.

Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.2094104.

1 Corresponding author.
E-MAIL dione_kampa{at}affymetrix.com; FAX (408) 481-0422.

[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 The following individuals kindly provided unpublished information as indicated in the paper: K. Cole, V. Truong, D. Barone, G. McGall, H.H. Ng, E.A. Sekinger, A.J. Williams, R. Wheeler, B. Wong, and K. Struhl.]


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