TRANSCRIPTOME 2002: From Functional Genomics to Systems
RNA Transcription Detected on Chromosomes 21 and 22 Using High Density Oligonucleotide Arrays
Thomas R. Gingeras, Affymetrix Inc., Santa Clara, CA
The first drafts of complete human genome sequence have brought with them the opportunities to map the RNA transcription patterns that are characteristic of each differentiated and undifferentiated cell type and characterize the sequence variations that underlie the phenotypic differences observed in the human population. By using the very high information content inherent in high-density oligonucleotide arrays it will be possible to map the locations of RNA transcription along the length of the entire human genome. Such a transcriptome map will provide information concerning: 1) the identification of novel transcription domains of the genome, 2) the predominant utilization of exon sequences during differentially spliced gene expression and 3) a empirically derived set of results which can be compared to the sequence annotation now being assembled for the human genome. Initial experiments have been focused on mapping the transcription domains originating from chromosomes 21 and 22. Oligonucleotide probes of 25 nucleotides in length have been selected to interrogate the non-repetitive nucleotide sequences within these chromosomes at a resolution of approximately 35 base pairs (measured from the central positions of each adjoining probe). A total of three arrays each of which contain ~400,000 probe pairs (probes designed to be perfect match and mismatch) are needed to interrogate ~35 Mb of non-repetitive sequences from these chromosomes. The map results when overlaid on to the sequence annotations available for these two chromosomes reveal that as much as an order of magnitude more of the genomic sequences are used for transcription than envisioned by the predicted and characterized exons. These transcripts represent a hidden transcriptome not accounted for in current annotated maps.
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