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.
Kampa
Dione
D
Affymetrix, Santa Clara, California 95051, USA. dione_kampa@affymetrix.com
Cheng
Jill
J
Kapranov
Philipp
P
Yamanaka
Mark
M
Brubaker
Shane
S
Cawley
Simon
S
Drenkow
Jorg
J
Piccolboni
Antonio
A
Bekiranov
Stefan
S
Helt
Gregg
G
Tammana
Hari
H
Gingeras
Thomas R
TR
D002460:Cell Line; D045744:Cell Line, Tumor; D002874:Chromosome Mapping / Q000379:methods; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D005796:Genes / Q000235:genetics; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015345:Oligonucleotide Probes / Q000235:genetics; D012313:RNA / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*
D004273:DNA, Neoplasm; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D012313:RNA