Biology Reference
In-Depth Information
vertebrates, coupled with the versatility and rapidity of Drosophila techniques,
makes them an ideal system for advancement of our understanding of neurological
disease mechanisms. Such progress may ultimately yield preventative treatments
for these disorders.
The completion and annotation of the genome sequence of
D. melano-
gaster
, 2000) and the availability of internet accessible homology
search algorithms make the identification of candidate Drosophila disease homo-
logs relatively trivial (e.g., see http://superfly.ucsd.edu/homophila/). Use of these
search algorithms indicates that the Drosophila genome encodes excellent
homologs for many of the currently identified PD-related genes (Table 1.1).
In particular, the Drosophila genome encodes genes highly homologous to
Dardarin
(Adams
et al.
/
LRRK2
,
parkin
,
PINK1
,
Omi
/
HtrA2
,
DJ-1
,
UCH-L1
,
GIGYF2
,
PLA2G6
, and
GBA
(Table 1.1). Notably, there is a clear lack of Drosophila
Table 1.1. Putative Function of Human Genes Linked to PD and Their Fly Homologs
Fly
homolog(s)
identity,
similarity
Mode of
inheritance
Fly homolog
CG#
Putative
function
PD locus
Gene/protein
PARK1
SNCA
/
AD
no homolog
no homolog
Synaptic plasticity?
PARK4
PARK2
-synuclein
Parkin
AR
parkin/
CG10523
42%, 59%
E3 ubiquitin-protein
ligase
PARK5
UCH-L1
AD(?)
Uch/
CG4265
45%, 66%
Ubiquitin hydrolase/
ligase
PARK6
PINK1
AR
CG4523
32%, 50%
Mitochondrial kinase
PARK7
DJ-1
AR
DJ-1 /
CG6646
56%, 70%
Oxidative stress sensor,
chaperone?
DJ-1/
CG1349
52%, 69%
PARK8
Dardarin/
LRRK2
AD
CG5483
26%, 43%
Kinase, GTPase
PARK9
ATP13A2
AR
no homolog
no homolog
Lysosome
PARK11 GIGYF2
AD
CG11148
50%, 71%
Insulin signaling
PARK13 Omi/HtrA2
AD(?)
HtrA2/
CG8464
51%, 70%
Serine protease
PARK14
PLA2G6
AR
CG6718/
iPLA2-
VIA
50%, 67%
Phospholipase
PARK15
FBXO7
AR
no homolog
no homolog
Protein complex
scaffolding
GBA
AD(?)
CG31414
31%, 49%
Glucocerebrosidase
CG31148
32%, 50%
