Download IMGT/GENE-DB: genomic reference sequences for human and

Im
Muno
Gene
Tics
IMGT/GENE-DB: genomic reference sequences for human and
mouse IG and TR genes and alleles
Fatena Bellahcene, Géraldine Folch, Joumana Jabado-Michaloud, Chantal Ginestoux, Patrice Duroux,
Véronique Giudicelli and Marie-Paule Lefranc
IMGT®, the international ImMunoGeneTics information system®, Laboratoire d’ImmunoGénétique Moléculaire LIGM, Université Montpellier 2,
Institut de Génétique Humaine IGH, CNRS UPR 1142, 141 rue de la Cardonille, F-34396 Montpellier cedex 05, France
Information
system®
http://www.imgt.org
The immunoglobulin (IG) and T cell receptor (TR) major loci span about 6 Megabases (Mb) of the human genome on chromosomes 2, 7, 14 and 22, and 9 Mb in mouse on chromosomes 6, 12, 13, 14 and 16.
There are seven major loci: three IG loci (IGH, IGK, IGL) and four TR loci (TRA, TRB, TRG, TRD), with a distinct repartition of the variable (V), diversity (D), joining (J) and constant (C) genes. The human
genome comprises a total number of 608-665 IG and TR genes (371-422 IG and 237-243 TR), depending on the haplotypes, per haploid genome [1, 2] of which 531-588 genes are located in the major loci
(distributed in 369-418 V, 32 D, 105-109 J and 25-29 C genes). There are also 77 orphons (68 IG and 9 TR) including two processed IG genes, outside the major loci. The number of functional IG and TR
genes is 308-356 (136-171 IG and 172-185 TR) per haploid genome. The mouse genome comprises an approximate number of 876 IG and TR genes (624 IG and 252 TR). All these genomic data are available
in the IMGT® gene database, IMGT/GENE-DB [3]. The major contribution of IMGT/GENE-DB has been to establish, for the first time, a standardized nomenclature of the IG and TR genes and alleles of humans
and other vertebrates. In April 2009, IMGT/GENE-DB manages 1999 genes and 3026 alleles.
[1] Lefranc M.-P. and Lefranc G., The Immunoglobulin FactsBook, Academic Press, London, 458 pages (2001).
[2] Lefranc M.-P. and Lefranc G., The T cell receptor FactsBook, Academic Press, London, 398 pages (2001).
[3] Giudicelli V. et al. Nucleic Acids Res., 33, D256-261 (2005).
IMGT/GENE-DB
specificity
sequences
IMGT/GeneFrequency
IMGT/DomainDisplay
Genomic approach
Genetic approach
Structural approach
IMGT repertoire links
External links
IMGT/LIGM-DB
IMGT/DomainGapAlign
genes/reference sequences
IMGT/GeneInfo
IMGT/GeneSearch
IMGT/GeneView
IMGT/LocusView
loc gen
ali e
za
tio
n
Locus representations
Gene tables
IMGT Repertoire
Web resources
Protein Display
IMGT/Collier-de-Perles
IMGT/V-QUEST
gen
e
ide and
ntif alle
ic a
l
tion e
IMGT/CloneSearch
IMGT/
3Dstructure-DB
res
ctu
stru
/3D
nes
translation of IG and TR
constant genes
UnitProt
Alignments of alleles
HGNC
MGI
NCBI/GenBank
Wellcome Trust
Sanger Institute
Vega
EBI
Ensembl
Mouse Genome
Informatics
IMGT/GENE-DB provides
links to IMGT® sequence
database (IMGT/LIGM-DB)
and 3D structure database
(IMGT/3Dstructure-DB), to
IMGT® tools for sequences
(IMGT/V-QUEST,
IMGT/DomainGapAlign,
etc.), genomic data
(IMGT/GeneFrequency,
etc.), structural data
(IMGT/DomainDisplay,
etc.), and to IMGT
Repertoire Web resources
(Chromosomal localizations,
Locus representations,
Gene tables, etc.).
Human and mouse IG and
TR IMGT reference
sequences have been
provided to NCBI Entrez
Gene, Mouse Genome
Informatics (MGI), EBI
Ensembl and Wellcome
Trust Sanger Institute
Vega, for the human and
mouse genome IG and TR
annotation. The translation
of the IG and TR constant
genes was provided to
UniProt in 2008.
ge
IMGT/GENE-DB
DATABASE
1-68
(III)-67-4
(III)-67-2
(II)-67-1
1-67
3-66
(II)-65-1
3-65
1-69
3-71
2-70
3-72
3-73
3-74
(III)-76-1
3-76
3-75
(II)-74-1
7-77
5-78
(III)-82
7-81
4-80
3-79
(II)-78-1
IGK and IGL loci (not shown here)
are available in IMGT Repertoire
(http://www.imgt.org/textes/IMGT
repertoire)
1-24
3-23
(II)-22-1
3-22
3-6
3-7
(III)-5-2
(III)-5-1
2-5
1-8
J1 to J6
J1P
D7-27
4.5
Locus
~55
G4
18
E
23
A2
Enhancer
10
25
3'
1 250 kb
Allelic multigene duplications
Deletion I
Deletion II
Deletion III
Deletion IV
Deletion V
Deletion VI
Not found
Not found
III (also triplication)
IV
V
Not found
Chromosomal
localization
100
150
TRG 3’
TRGC : 1
TRGJ : 2
TRGC : 1
TRGJ : 3
JP
0
16
50
100
C1
C2
JP2 J2
Silencer
Enhancer
3'
1250
1820
500
1050
IGL
Total of functional
IG genes
IGH
IGK
ter
3’
150
200 kb
200 kb
50
100
150
Telomeric
30
T6 T7 T8
Enhancer
T4 T5
D1
J1-1 to J1-6
C1
D2
J2-1 to J2-7
C2
29-1
B
27
28
A
26
25-1
24-1
400 kb
21-1
22-1
23-1
L-PART1+V-EXON
nucleotides
amino acids
F+ORF+all P
F+ORF+in-frame P
nucleotides
amino acids
Locus and genes
Gene table
Locus representation
Proteins and alleles
Protein displays
123-129
(40d or) 76
73-74
236-279
27
0
0
27
9
5
7-11
21-25
11a
1
7-11
19-23
170-176b
(46d or) 82
87-96
303-354
Total number
of IG genes
including
orphons
206-212b,c
(71d or) 107
94-103
371-422c,e
Number of
orphons
36c
25
7e
68c,e
D
J
C
38-46
34-38
17-19d
29-33
101-117
84-98d
23
6
9a
0
5
1
0
4-5
4-5
Number of
functional
IG genes
76-84
40-44
23-25d
37-43
23
15-16
14-15
136d-171
Allelic IGHC multigene deletions, duplications and triplications have
been described in healthy individuals. The number of IGHC genes is
5 (deletions I, III, and V), 6 (deletions IV and VI), or 8 (deletion II),
per haploid genome.
In haplotypes with multigene duplication or triplication, the exact
number of functional IGHC genes per haploid genome is not known.
b
Not included the 7 non-mapped IGHV genes.
c
Included the IGHC processed gene, IGHEP2, localized on
chromosome 9 (9p24.2-24.1).
d
Number of genes in the rare IGKV haplotype without the distal
V-CLUSTER.
e
Included the IGLJ-C/OR18 processed gene, localized on
chromosome 18 (18p11.31).
a
CELL GENES
Chromosomal
localization
V
D
J
C
Total number
of genes
54a
64-67
42339
3 (8a)
133-139
0
2
0
3
5
61
14
5
4
84
1
2
2
1
6
116a
82-85
19-22
11 (16a)
228-234
Number of
orphons
0
9
0
0
9
Total number
of TR genes
including
orphons
116a
91-94
19-22
11 (16a)
237-243
The functional TR genes (172-185 depending on the haplotypes) are located in the 4 major TR loci. Different
molecular mechanisms (V-J and V-D-J rearrangements, N-diversity), unique to vertebrates, allow to create a huge
repertoire of 2x1012 TR per individual.
18
19
20-1
15
16
17
12-5
14
11-3
12-3
12-4
10-3
7-9
13
5-8
6-9
7-8
5-7
5-5
6-7
7-6
5-6
6-8
7-7
5-4
6-6
7-5
7-4
620 kb
(82-85 genes)
0
gDNA
IMGT Repertoire links :
Total number
of genes
14q11.2
TRA
7q34
TRB
7p14
TRG
14q11.2
TRD
Total number of genes
12-2
6-5
11-2
12-1
10-2
11-1
6-4
7-3
8-2
5-3
9
10-1
5'
TRA and TRD loci (not shown
here) are available in IMGT
Repertoire
(http://www.imgt.org/textes/IMGT
repertoire)
M34978
Number of functional TR genes
8-1
5-2
T3
P
C
Centromeric
6-3
7-2
TRB
IGHV1-58*02
J
5’ TRBD : 1
TRBJ : 6
TRBC : 1
TRBD : 1
TRBJ : 8
TRBC : 1
TRBV : 1
gDNA
IGHV1S48,VH1.3
F+ORF+in-frame P with IMGT gaps
nucleotides
Major loci
Locus
TRB locus at 7q34
TRBV : 63-66
AC087166
A/J
V-REGION
F+ORF+all P
D
200 kb
40 kb
160 kb
(19-22 genes)
cen
Accession numbers Molecule type
Total number of TR genes
5’ TRGV : 12-15
3-2
4-3
q
21
15.2
14
13
12
11.2 11.1
11.21 11.1
11.22
11.23
21.1
21.2 21.3
22
31.1
31.2
31.3
32
33
34
35
36
15.3
15.1
10 B 11
100 kb
4-2
6-2
p
-
The human genome comprises 237-243 TR genes (228-234 genes located in the 4 major TR loci and 9 orphons), per
haploid genome.
Telomeric
JP1 J1
3P
ter
F
200 kb
Vg III Vg IV
Vg II
5 5P 6 7 8 A 9
1
2
3-1
4-1
5-1
6-1
7-1
22
Vg I
1 2 3 4
5'
Gene
functionality
IGHV1-58*01
V
TRG locus at 7p14
7
IGHV1-58 allele names
V
Locus
size (kb)
HUMAN T
Centromeric
C57BL/6
IMGT/GENE-DB reference sequences (in FASTA format)
GLVR1
(II)-44-2
(IV)-44-1 (III)-67-3
(III)-44
(II)-43-1
3-43
3-42
3-48
25
50
Clone names
The functional IG genes (136-171 depending on the haplotypes) are located in the 3 major IG loci. Different
molecular mechanisms (V-J and V-D-J rearrangements, N-diversity, and for IG, somatic hypermutations), unique to
vertebrates, allow to create a huge repertoire of 2x1012 IG (or antibodies) per individual.
Allelic multigene deletions
0
P
+
Strain
600 kb
1 000 kb
~60
Enhancer
G2
GP
Enhancer
13
IGHV1-58*02
Pr
Number of functional IG genes
M D
KIAA
EP1 A1
19
F
T
D5-18
D3-10
D5-12
D1-1
D2-2
D3-3
D4-4
D5-5
D6-6
D1-7
D2-8
D3-9
D4-11
D6-13
D1-14
D2-15
D3-16
D4-17
D6-19
D1-20
D2-21
D3-22
D4-23
D5-24
D6-25
D1-26
G1
26
IGHV1-58*01
IMGT/LIGM-DB reference sequences
R
14q32.33
IGH
2p11.2
IGK
22q11.2
IGL
Total number of genes
Centromeric
G3
Gene
functionality
Major loci
(III)-22-2
(III)-25-1
3-25
2-26
3-9
2-10
3-13
Golgin
1-12
(III)-11-1
3-11
3-15
1-14
(III)-13-1
Golgin
1-18
GLVR1
1-17
(III)-16-1
3-16
(II)-15-1
(II)-20-1
3-20
3-19
MDC
5’
(II)1-1
6-1
1 250 kb
(170-176 genes)
IGHV1-58 allele
names
Locus
800 kb
1-2
S8
ter
2
IMGT reference alleles :
400 kb
4-30-1
4-30-2
3-30-3
4-30-4
3-30-5
3-37
3-36
3-35
7-34-1
4-34
3-33-2
(II)-33-1
3-33
3-32
(II)-31-1
4-31
3-30-2
(II)-30-1
3-30
3-29
(II)-28-1
4-28
7-27
(II)-26-2
(III)-26-1
7-40
4-39
(III)-38-1
3-38
3-41
(II)-40-1
IGH
3-21
IGHC : 11
IGHJ : 9
IGHD : 27
IGHV : 123-129
Number of alleles:
200 kb
cen
3’
Mus musculus IGH locus
12
12 (58.0 cM)
The human genome comprises 371-422 IG genes (303-354 genes located in the 3 major IG loci and 68 orphons), per
haploid genome.
(II)-51-2
(III)-47-1
3-47
(II)-46-1
1-46
1-45
7-56
4-55
3-54
(II)-53-1
3-53
3-52
(III)-51-1
5-51
3-50
(II)-49-1
3-49
3-64
3-63
(II)-62-1
3-62
4-61
(II)-60-1
3-60
4-59
1-58
3-57
ter
7-4-1
q
11.1
11.1
11.2
12
13
21
22
23
24.1 24.2
24.3
31
32.1 32.2
32.3
4-4
1-3
(III)-2-1
p
Golgin
14
12
Locus name :
Chromosome :
Chromosomal localization :
Total number of IG genes
5'
11.2
An IMGT/GENE-DB entry includes
IMGT gene name and definition,
Chromosomal localization,
Number of alleles, IMGT reference
alleles, IMGT Repertoire links and
table of annotated cDNA
sequences in IMGT/LIGM-DB and,
if available, protein structures in
IMGT/3Dstructure-DB.
Mus musculus IGHV1-58
Immunoglobulin heavy variable 1-58
Chromosomal localization
IMMUNOGLOBULIN GENES
IGH locus at 14q32.3
13
IMGT gene name :
IMGT gene definition :
Annotated IMGT/LIGM-DB cDNA sequences for Mus musculus IGHV1-58: 2
HUMAN
Telomeric
IMGT/GENE-DB entry for Mus musculus IGHV1-58
IMGT gene name and definition
3'
620 kb
200 kb
IMGT founder and director: Marie-Paule Lefranc ([email protected])
Bioinformatics manager: Véronique Giudicelli ([email protected])
Computer manager: Patrice Duroux ([email protected])
Interface design: Chantal Ginestoux ([email protected])
© Copyright 1995-2009 IMGT®, the international ImMunoGeneTics information system®
Locus
Locus
size (kb)
1000
TRA
620
TRB
160
TRG
b
TRD
60 (530c)
Total of functional
TR genes
Number of
functional
TR genes
V
D
J
C
43-45a
40-48
4-6
3 (7-8a)
0
2
0
3
50
41609
5
4
1
2
2
1
11 (15-16a)
90-102
5
71-72
6
172-185
94-96a
56-65
41579
Including 5 TRAV/TRADV genes. These 5 genes are counted once.
The number of functional TRAV and TRDV genes in the TRA/TRD
locus is 46-48. The total number of the functional genes for the
TRA/TRD locus is 105-107.
b
Size of the cluster from TRDV2 to TRDV3.
c
Distance between the most 5' TRAV/DV gene (TRAV14/DV4) and
the most 3' gene of the TRD locus (TRDV3).
d
Taking into account the rearrangement with 2 or 3 TRDD (4
possible combinations: D1,D2; D1,D3; D2,D3; D1,D2,D3).
a
IMGT® is funded by CNRS, MESR and EU ImmunoGrid IST-2004-028069
© 2009 F.Bellahcene and M-P.Lefranc