Global View of Gene Activity and Alternative Splicing by Deep Sequencing of the Human Transcriptome

• Published in: Science (American Association for the Advancement of Science) Vol. 321; no. 5891; pp. 956 - 960
• Main Authors: Sultan, Marc, Schulz, Marcel H, Richard, Hugues, Magen, Alon, Klingenhoff, Andreas, Scherf, Matthias, Seifert, Martin, Borodina, Tatjana, Soldatov, Aleksey, Parkhomchuk, Dmitri, Schmidt, Dominic, O'Keeffe, Sean, Haas, Stefan, Vingron, Martin, Lehrach, Hans, Yaspo, Marie-Laure
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 15.08.2008; The American Association for the Advancement of Science
• Subjects: Alternative Splicing; B lymphocytes; Biological and medical sciences; Cell Line; Cell Line, Tumor; Cell lines; Cells; Cellular biology; Computational Biology; DNA, Complementary; DNA, Intergenic; Exons; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Genes; Genome, Human; Genomes; Genomics; high-throughput nucleotide sequencing; Human body; Humans; Intergenic DNA; Introns; Kidneys; microarray technology; Molecular and cellular biology; Molecular genetics; Oligonucleotide Array Sequence Analysis; Ribonucleic acid; RNA; RNA Polymerase II - metabolism; RNA Splice Sites; RNA, Messenger - genetics; Sequence Analysis, RNA; surveys; Transcription. Transcription factor. Splicing. Rna processing; transcriptome; Human; Alternative splicing; Embryo; Urinary system; Nucleotide sequence; Transcriptome; B-Lymphocyte; Gene expression; Kidney
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1160342

The functional complexity of the human transcriptome is not yet fully elucidated. We report a high-throughput sequence of the human transcriptome from a human embryonic kidney and a B cell line. We used shotgun sequencing of transcripts to generate randomly distributed reads. Of these, 50% mapped to unique genomic locations, of which 80% corresponded to known exons. We found that 66% of the polyadenylated transcriptome mapped to known genes and 34% to nonannotated genomic regions. On the basis of known transcripts, RNA-Seq can detect 25% more genes than can microarrays. A global survey of messenger RNA splicing events identified 94,241 splice junctions (4096 of which were previously unidentified) and showed that exon skipping is the most prevalent form of alternative splicing.