Human Chromosome 10 - uoc.gr
Transcript of Human Chromosome 10 - uoc.gr
Human Chromosome 10 (Aug 2003)
Size: 133 Mb, p/q arm: 35/92 MbFinishedsequence: ~ 124 MB Percentage: 86 %
Assembly completion status
> 5 Mb> 1 Mb
> 0.5 Mb
> 0.1 Mb
> 0.01 Mb
> 50% in golden path
Molecular function of 292 HC10 RefSeq proteins
Euchromatin: ~129 Mb Hetetochromatic region: 3.3-4 Mb
Gene density: ~ 8 genes/MbGenes: 1060G+C content: 42% CpG density: 8.2 islands/MbRepeats: ~43%
Microsatellite density: 4 microsatellites/MbSNP density: 460 SNPs/Mb
Disease genes: 53; clinical phenotypes: 75 Multifactorial disease susceptibility loci: 10 Fragile sites: 7 (2 rare)
heterochromatin
draft seq.
> 1 Mb0.25-1 Mb< 0.25 Mb
Sequencing progress
0%
5%
10%
15%
20%
25%
Cellular
proc
esse
s
Metabo
lism
DNA/RNA mod
ificatio
n
Trans
cription
/Tran
slation Sig
naling
Cell-cel
l commun
ication
Protein
mod
ificatio
nTra
nspo
rt
Cytos
keleta
l
Defens
e/Immun
ity
Cell cy
cle
HC10All HCs
www.ensembl.org/Homo_sapiens/
http://www.sanger.ac.uk/HGP/Chr10/
Physical and genic map of the EPT/ADLTE
critical region (3,5 Mb)
ter
hDHDPS-like
bA56
2L21
bA31
3N18
bA30
E16
bA43
7J2
bA51
2J3
bA39
7J18
bA42
9H9
bA16
2K11
bA39
1J2
bA76
P2
bA14
6P21
bA11
9K6
bA36
1K9
bA40
0G3
bA20
8C17
bA31
0E22
bA16
0P20
bA47
6E15
bA16
4I17
bA7D
5bA
429G
19bA
690P
14bA
44D
15bA
533B
2bA
35J2
3bA
304C
14bA
34E
5bA
196N
24bA
153G
4bA
175O
19bA
208M
2bA
375N
9bA
452K
12bA
445I
23bA
548K
23bA
459F
3
RBP4PDE6C
LGI1CYP2C18
CYP2C9
CYP2C8
CLIM1
PYCS
CD39 DNTT
SLIT1
FRAT1
cenFER1L3
FLJ10540
FRA10AC1
PLCE
AD24
KIAA0608
SMARCA6
CYP2C19 SORBS1
BLNKHTMP10
TLL2
emp70
FRAT2
KIAA0690PGAM1
hCSL4
3077hMMS19FLJ11807
ANKRD2
44050
LOC159371
AL050022
KIAA1795
FLJ13022
SPG9 (~7Mb)
EPT (~3,2Mb)
SHFM3(~1,5Mb)
FRA10A
NEURL
NT
_008
769
(6.7
Mb
)N
T_0
3005
9 (2
0 M
b) 10
q23
.3-q
24
Mutations in LGI1 cause AD lateral temporal lobe epilepsy (EPT)
1 2 3 4 5 7 8
ATG STOP
1639insA
1050-1051delCA1148AgC
6
611delC
IVS3(-3)CgA
598TgC
758delC 1420CgT
136TgC
Normal 557aa
IVS3(-3)CgA 120aa136TgC C46R*
C200R**598TgC238aa (203+35 missense)611delC
758delC 283aa (252+31 missense)**1050-1 delCA 379aa (349+30 missense)
1148AgC E383A1420CgT 473aa**1639insA
553aa (546+7 missense)
EPTP repeatsLRR
LRR-NT LRR-CT
•auditory symptoms, short-lasting sensory aphasia
** auditory symptoms, visual hallucinations
European Consortium for EPT
R. Ottman et. al.
O. Steinlein et al.
Expression of mLgi1 in adult mouse brain
hippocampusCortical layers
Coronal image of half brain
Expression of mLgi1 in synaptic terminals
Adult mouse brain Embryonic neurons (cell bodies and neurites)
Expression of hLGI1 in human temporal and frontal cortex
Temporal cortex Frontal cortex
2002
The superfamily of EPTP genes
LGI family (1-4) TNEP1
VLGR1500aa
Gene Chromosome location Description
LGI1 10q24 Temporal lobe partial epilepsy
LGI2 4p15.2 Expressed in brain
LGI3 8p21 Expressed in brain/ Torsion dystonia (DYT6)
LGI4 19q13.12 Benign familial infantile convulsions (hereditary epilepsy
VLGR1 5q14 Familial febrile convulsions type 4
TNEP1 21q22.3 Myoclonus epilepsy EPM1/Down syndrome critical region/MR
EPTP repeat: a protein interaction domain that links several genes implicated in neurological diseases
Very large G-protein-coupled receptor
ThrombospondinN-terminal domain-EPTP
EMITTING CELL
RECEIVING CELL nucleus
Not
ch
Del
taNe
uraliz
ed
TACEpresenilin
Del
ta
?
Del
taN
otch
Neu
raliz
ed
Ub
Not
ch
?Endocytic vesicle
Dm neuralized (Neur) protein-is an intracellular peripheral membrane protein-stimulates Delta endocytosis and Notch signaling-RING domain is required for Delta accumulation in endosomes but dispensable for Delta signaling;-acts as an E3 ubiquitin ligase
Nec Nec
Dl Dl
Delta over-expressed
Delta + Neur over-expressed
neur
Dm neuralized (neur):- a neurogenic gene implicated in Dm process of sense organ formation
- neur mutations cause hyperplasia of the central & peripheal nervous system, mimicing the excessive neurogenesis phenotype of Notchmutations
mergemerge
The role of drosophila neuralized in Notch signaling
Human NEURL
Drosophila neur
94%
id
enti
ty
Neuralized proteins
RING Zn finger
Mouse Neurl1 574
100 200
NEUZ 1
60 183
300 400 500
291 414 521 560
NEUZ 2
574100 200
60 183
300 400 500
291 414 521 560
1
522 616 73 94
7541143 242
264 292 55 69
104 225
377 680475
366 489 701 741
3 7
15 18
629 637 38 39
314 318367 36930
% i
den
tity
(sim
ilari
ty 5
7%)
(574aa)
(574aa)
(754aa)
neur/EGFPNeurl/EGFP neur/EGFPNeurl/EGFP
Subcellular localization in mammalian cell linesSubcellular localization in Drosophila
neur