Integrative annotation of 21,037 human genes validated by full-length cDNA clones.
The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
Imanishi
Tadashi
T
Integrated Database Group, Biological Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
Itoh
Takeshi
T
Suzuki
Yutaka
Y
O'Donovan
Claire
C
Fukuchi
Satoshi
S
Koyanagi
Kanako O
KO
Barrero
Roberto A
RA
Tamura
Takuro
T
Yamaguchi-Kabata
Yumi
Y
Tanino
Motohiko
M
Yura
Kei
K
Miyazaki
Satoru
S
Ikeo
Kazuho
K
Homma
Keiichi
K
Kasprzyk
Arek
A
Nishikawa
Tetsuo
T
Hirakawa
Mika
M
Thierry-Mieg
Jean
J
Thierry-Mieg
Danielle
D
Ashurst
Jennifer
J
Jia
Libin
L
Nakao
Mitsuteru
M
Thomas
Michael A
MA
Mulder
Nicola
N
Karavidopoulou
Youla
Y
Jin
Lihua
L
Kim
Sangsoo
S
Yasuda
Tomohiro
T
Lenhard
Boris
B
Eveno
Eric
E
Suzuki
Yoshiyuki
Y
Yamasaki
Chisato
C
Takeda
Jun-ichi
J
Gough
Craig
C
Hilton
Phillip
P
Fujii
Yasuyuki
Y
Sakai
Hiroaki
H
Tanaka
Susumu
S
Amid
Clara
C
Bellgard
Matthew
M
Bonaldo
Maria de Fatima
Mde F
Bono
Hidemasa
H
Bromberg
Susan K
SK
Brookes
Anthony J
AJ
Bruford
Elspeth
E
Carninci
Piero
P
Chelala
Claude
C
Couillault
Christine
C
de Souza
Sandro J
SJ
Debily
Marie-Anne
MA
Devignes
Marie-Dominique
MD
Dubchak
Inna
I
Endo
Toshinori
T
Estreicher
Anne
A
Eyras
Eduardo
E
Fukami-Kobayashi
Kaoru
K
Gopinath
Gopal R
GR
Graudens
Esther
E
Hahn
Yoonsoo
Y
Han
Michael
M
Han
Ze-Guang
ZG
Hanada
Kousuke
K
Hanaoka
Hideki
H
Harada
Erimi
E
Hashimoto
Katsuyuki
K
Hinz
Ursula
U
Hirai
Momoki
M
Hishiki
Teruyoshi
T
Hopkinson
Ian
I
Imbeaud
Sandrine
S
Inoko
Hidetoshi
H
Kanapin
Alexander
A
Kaneko
Yayoi
Y
Kasukawa
Takeya
T
Kelso
Janet
J
Kersey
Paul
P
Kikuno
Reiko
R
Kimura
Kouichi
K
Korn
Bernhard
B
Kuryshev
Vladimir
V
Makalowska
Izabela
I
Makino
Takashi
T
Mano
Shuhei
S
Mariage-Samson
Regine
R
Mashima
Jun
J
Matsuda
Hideo
H
Mewes
Hans-Werner
HW
Minoshima
Shinsei
S
Nagai
Keiichi
K
Nagasaki
Hideki
H
Nagata
Naoki
N
Nigam
Rajni
R
Ogasawara
Osamu
O
Ohara
Osamu
O
Ohtsubo
Masafumi
M
Okada
Norihiro
N
Okido
Toshihisa
T
Oota
Satoshi
S
Ota
Motonori
M
Ota
Toshio
T
Otsuki
Tetsuji
T
Piatier-Tonneau
Dominique
D
Poustka
Annemarie
A
Ren
Shuang-Xi
SX
Saitou
Naruya
N
Sakai
Katsunaga
K
Sakamoto
Shigetaka
S
Sakate
Ryuichi
R
Schupp
Ingo
I
Servant
Florence
F
Sherry
Stephen
S
Shiba
Rie
R
Shimizu
Nobuyoshi
N
Shimoyama
Mary
M
Simpson
Andrew J
AJ
Soares
Bento
B
Steward
Charles
C
Suwa
Makiko
M
Suzuki
Mami
M
Takahashi
Aiko
A
Tamiya
Gen
G
Tanaka
Hiroshi
H
Taylor
Todd
T
Terwilliger
Joseph D
JD
Unneberg
Per
P
Veeramachaneni
Vamsi
V
Watanabe
Shinya
S
Wilming
Laurens
L
Yasuda
Norikazu
N
Yoo
Hyang-Sook
HS
Stodolsky
Marvin
M
Makalowski
Wojciech
W
Go
Mitiko
M
Nakai
Kenta
K
Takagi
Toshihisa
T
Kanehisa
Minoru
M
Sakaki
Yoshiyuki
Y
Quackenbush
John
J
Okazaki
Yasushi
Y
Hayashizaki
Yoshihide
Y
Hide
Winston
W
Chakraborty
Ranajit
R
Nishikawa
Ken
K
Sugawara
Hideaki
H
Tateno
Yoshio
Y
Chen
Zhu
Z
Oishi
Michio
M
Tonellato
Peter
P
Apweiler
Rolf
R
Okubo
Kousaku
K
Wagner
Lukas
L
Wiemann
Stefan
S
Strausberg
Robert L
RL
Isogai
Takao
T
Auffray
Charles
C
Nomura
Nobuo
N
Gojobori
Takashi
T
Sugano
Sumio
S
D017398:Alternative Splicing / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D018076:DNA, Complementary / Q000235:genetics*; D030541:Databases, Genetic; D005796:Genes / Q000235:genetics / Q000502:physiology*; D015894:Genome, Human; D006801:Humans; D020407:Internet; D018895:Microsatellite Repeats / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary
D018076:DNA, Complementary