Transcript The human "ferlin" genes

The human “ferlin” genes
DYSF
OTOF
FERLIN-10
2p13
7 kb
skeletal
brain
LGMD2B, MM
2p23
6 kb
inner ear,
placenta
DFNB9
10q23.3
7.5 kb
heart, lung, muscle
?
Structure of the “ferlins”
FER-1
DYSF OTOF
C2 domains
6
6
3
C-terminal anchor
+
+
+
Homology with FER-1
28%
30%
FERLIN-10
6
+
40%
Disease genes mapped to 10q23
Several tumour suppressor genes
PTEN/MMAC1, Mxl1, RET
Intestinal polyposis syndrome
Congenital erythropoietic porphyria
Dilated cardiomyopathy, CMD1C
Apert syndrome
Current and future research on the
“ferlins”
Molecular genetic characterisation
Expression analysis
Role in disease
Subcellular localisation
Interacting proteins
Characterisation of the C2 domains
Analysis of the yeast “ferlins”
The SJL/J mouse is the natural model
for dysferlinopathy
experimental model for MS
non-sensitised mice have a progressive muscular
dystrophy
inherited as autosomal recessive
mapped to mouse chromosome 6
affected mouse muscle is deficient for dysferlin
Ferlin-10 is highly similar to dysferlin
• amino acid sequence is >60% homologous to
dysferlin
• transcript sizes are similar
• expression in human and mouse dysferlinopathy
to be determined
• role as a potential modifier of dysferlinopathy
needs to be explored