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

Genome Res. 2004 Mar;14(3):331-42. doi: 10.1101/gr.2094104.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Validation Study

MeSH terms

  • Cell Line
  • Cell Line, Tumor
  • Chromosome Mapping / methods
  • Chromosomes, Human, Pair 21 / genetics*
  • Chromosomes, Human, Pair 22 / genetics*
  • DNA, Neoplasm / genetics
  • Gene Expression Profiling / methods
  • Genes / genetics
  • Genes, Neoplasm / genetics
  • Humans
  • Jurkat Cells / chemistry
  • Jurkat Cells / metabolism
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis / methods
  • Oligonucleotide Probes / genetics
  • RNA / genetics*
  • RNA, Messenger / genetics
  • Transcription, Genetic / genetics*

Substances

  • DNA, Neoplasm
  • Oligonucleotide Probes
  • RNA, Messenger
  • RNA

Associated data

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