Large-scale identification and characterization of alternative splicing variants of human gene transcripts using 56,419 completely sequenced and manually annotated full-length cDNAs.
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.
Takeda
Jun-ichi
J
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.
Suzuki
Yutaka
Y
Nakao
Mitsuteru
M
Barrero
Roberto A
RA
Koyanagi
Kanako O
KO
Jin
Lihua
L
Motono
Chie
C
Hata
Hiroko
H
Isogai
Takao
T
Nagai
Keiichi
K
Otsuki
Tetsuji
T
Kuryshev
Vladimir
V
Shionyu
Masafumi
M
Yura
Kei
K
Go
Mitiko
M
Thierry-Mieg
Jean
J
Thierry-Mieg
Danielle
D
Wiemann
Stefan
S
Nomura
Nobuo
N
Sugano
Sumio
S
Gojobori
Takashi
T
Imanishi
Tadashi
T
D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods; D018076:DNA, Complementary / Q000737:chemistry*; D005091:Exons; D014644:Genetic Variation; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D006801:Humans; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism; D017422:Sequence Analysis, DNA
D018076:DNA, Complementary; D011506:Proteins; D012333:RNA, Messenger