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Nucleic Acids Research Advance Access originally published online on August 12, 2006
Nucleic Acids Research 2006 34(14):3917-3928; doi:10.1093/nar/gkl507
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Nucleic Acids Research, 2006, Vol. 34, No. 14 3917-3928
© 2006 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Genomics

Large-scale identification and characterization of alternative splicing variants of human gene transcripts using 56 419 completely sequenced and manually annotated full-length cDNAs

Jun-ichi Takeda1,2, Yutaka Suzuki3, Mitsuteru Nakao4,5, Roberto A. Barrero6, Kanako O. Koyanagi7, Lihua Jin6, Chie Motono4, Hiroko Hata3, Takao Isogai8,9, Keiichi Nagai9,10, Tetsuji Otsuki9, Vladimir Kuryshev11, Masafumi Shionyu12, Kei Yura13,14, Mitiko Go11,15, Jean Thierry-Mieg16,17, Danielle Thierry-Mieg16,17, Stefan Wiemann11, Nobuo Nomura2, Sumio Sugano3, Takashi Gojobori2,6 and Tadashi Imanishi2,7,*

1 Integrated Database Group, Japan Biological Information Research Center, Japan Biological Informatics Consortium, AIST Bio-IT Research Building Aomi 2-42, Koto-ku, Tokyo 135-0064, Japan 2 Biological Information Research Center, National Institute of Advanced Industrial Science and Technology, AIST Bio-IT Research Building Aomi 2-42, Koto-ku, Tokyo 135-0064, Japan 3 Department of Medical Genome Sciences, Graduate School of Frontier Sciences, the University of Tokyo 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan 4 Computational Biology Research Center, National Institute of Advanced Science and Technology, AIST Bio-IT Research Building Aomi 2-42, Koto-ku, Tokyo 135-0064, Japan 5 Kazusa DNA Research Institute 2-6-7 Kazusa-Kamatari, Kisarazu, Chiba 292-0818, Japan 6 Center for Information Biology and DDBJ, National Institute of Genetics 1111 Yata, Mishima, Shizuoka 411-8540, Japan 7 Graduate School of Information Science and Technology, Hokkaido University North 14, West 9, Kita-ku, Sapporo, Hokkaido 060-0814, Japan 8 Reverse Proteomics Research Institute, 2-6-7 Kazusa-Kamatari Kisarazu, Chiba 292-0818, Japan 9 Helix Research Institute, Inc. 1532-3 Yana, Kisarazu, Chiba 292-0812, Japan 10 Central Research Laboratory, Hitachi Ltd 1-280, Higashi-koigakubo, Kokubunji-shi, Tokyo 185-8601, Japan 11 Division of Molecular Genome Analysis, German Cancer Research Center Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany 12 Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology 1266 Tamura-cho, Nagahama, Shiga 526-0829, Japan 13 Quantum Bioinformatics Team, Center for Computational Science and Engineering, Japan Atomic Energy Agency 8-1 Umemidai, Kizu, Souraku, Kyoto 619-0215, Japan 14 Core Research for Evolution Science and Technology, Japan Science and Technology Agency Japan 15 Ochanomizu University 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan 16 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health Bethesda, MD, USA 17 Centre National de la Recherche Scientifique, Laboratoire de Physique Mathematique Montpellier, France

*To whom correspondence should be addressed. Tel: +81 3 3599 8800; Fax: 81 3 3599 8801; Email: imanishi{at}jbirc.aist.go.jp

Received April 22, 2006. Revised July 3, 2006. Accepted July 3, 2006.

We report the first genome-wide identification and characterization of alternative splicing in human gene transcripts based on analysis of the full-length cDNAs. Applying both manual and computational analyses for 56 419 completely sequenced and precisely annotated full-length cDNAs selected for the H-Invitational human transcriptome annotation meetings, we identified 6877 alternative splicing genes with 18 297 different alternative splicing variants. A total of 37 670 exons were involved in these alternative splicing events. The encoded protein sequences were affected in 6005 of the 6877 genes. Notably, alternative splicing affected protein motifs in 3015 genes, subcellular localizations in 2982 genes and transmembrane domains in 1348 genes. We also identified interesting patterns of alternative splicing, in which two distinct genes seemed to be bridged, nested or having overlapping protein coding sequences (CDSs) of different reading frames (multiple CDS). In these cases, completely unrelated proteins are encoded by a single locus. Genome-wide annotations of alternative splicing, relying on full-length cDNAs, should lay firm groundwork for exploring in detail the diversification of protein function, which is mediated by the fast expanding universe of alternative splicing variants.


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