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IJ
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SN:
2252
-
8938
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o
n
y
m
o
u
s
m
u
tatio
n
s
ar
e
t
h
e
s
ile
n
t
m
u
tatio
n
s
t
h
at
t
h
e
v
ar
ian
t
w
i
ll
n
o
t
s
h
o
w
a
m
e
n
d
i
n
t
h
e
a
m
in
o
ac
id
s
.
Sil
e
n
t
m
u
tatio
n
s
ar
e
a
ch
a
n
g
e
i
n
co
d
o
n
t
h
at
e
n
co
d
es
f
o
r
t
h
e
s
a
m
e
a
m
i
n
o
ac
i
d
an
d
t
h
er
ef
o
r
e
t
h
e
tr
an
s
lated
p
r
o
tein
i
s
n
o
t
m
o
d
i
f
ied
[
1
1
]
.
I
n
d
etec
ti
n
g
t
h
e
t
y
p
e
o
f
d
i
s
ea
s
e
it
i
s
n
ec
es
s
ar
y
to
co
n
s
id
er
t
h
e
s
ile
n
t
m
u
tatio
n
a
s
th
e
c
h
a
n
g
e
s
ca
n
a
f
f
ec
t
p
r
o
tein
f
o
ld
i
n
g
a
n
d
f
u
n
c
tio
n
.
E
v
e
n
th
o
u
g
h
s
ev
er
al
co
d
o
n
s
en
co
d
e
f
o
r
t
h
e
s
a
m
e
a
m
i
n
o
ac
id
t
h
eir
f
r
eq
u
e
n
c
y
w
ill
v
ar
y
an
d
th
i
s
i
s
r
e
f
er
r
ed
as
co
d
o
n
b
ias.
T
h
e
in
cr
ea
s
e
in
t
h
e
n
u
m
b
er
o
f
th
e
s
a
m
e
n
u
cleo
tid
es
i
n
a
lo
c
atio
n
is
ter
m
ed
a
s
d
u
p
licatio
n
s
.
Dele
tio
n
s
ar
e
t
h
e
m
u
tatio
n
s
w
h
e
n
a
b
ase
o
r
a
n
ex
o
n
is
d
elete
d
f
r
o
m
a
s
eq
u
e
n
ce
th
e
m
u
tatio
n
s
.
[
1
2
]
.
Mu
s
cle
b
io
p
s
y
a
n
d
DN
A
te
s
ti
n
g
ar
e
i
n
p
r
o
g
r
e
s
s
f
o
r
d
ia
g
n
o
s
in
g
m
u
s
cu
lar
d
y
s
tr
o
p
h
y
[
1
3
]
.
An
i
n
it
ial
s
tep
in
ex
a
m
i
n
i
n
g
m
u
s
c
u
lar
d
y
s
tr
o
p
h
y
i
s
t
h
r
o
u
g
h
g
e
n
etic
te
s
tin
g
.
T
h
e
ad
v
an
ta
g
e
o
f
p
er
f
o
r
m
i
n
g
g
e
n
etic
test
in
g
o
v
er
m
u
s
c
le
b
io
p
s
y
is
t
h
at
i
n
g
en
et
ic
te
s
ti
n
g
,
th
e
b
lo
o
d
s
a
m
p
le
is
e
n
o
u
g
h
to
s
p
o
t
th
e
alter
at
io
n
i
n
t
h
e
g
e
n
e
s
w
h
er
ea
s
t
h
e
p
ar
t
o
f
th
e
tis
s
u
e
is
r
eq
u
ir
ed
to
p
er
f
o
r
m
t
h
e
m
u
s
cle
b
io
p
s
y
.
[
1
4
]
.
Gen
e
th
er
ap
y
h
elp
s
in
k
n
o
w
in
g
th
e
ex
ac
t
m
u
tatio
n
i
n
t
h
e
DM
D
g
en
e
a
n
d
d
ir
ec
t
s
eq
u
en
ci
n
g
aid
s
in
id
en
ti
f
y
i
n
g
m
i
s
s
e
n
s
e,
n
o
n
s
en
s
e,
in
s
er
tio
n
s
,
d
eletio
n
s
an
d
s
p
lici
n
g
m
u
tat
io
n
s
[
1
5
,
1
6
]
.
A
ll
s
o
r
t
o
f
m
u
tatio
n
s
ca
n
n
o
t
b
e
id
e
n
ti
f
ied
o
u
t
u
s
i
n
g
M
u
ltip
le
x
L
i
g
atio
n
-
d
ep
en
d
en
t
P
r
o
b
e
Am
p
li
f
icatio
n
(
ML
P
A
)
an
d
i
n
s
o
m
e
ca
s
es,
t
h
e
r
es
u
lts
w
o
u
ld
b
e
n
eg
ati
v
e
[
1
7
]
.
I
n
th
e
ca
s
e
o
f
DM
D,
S
NV’
s
ar
e
d
etec
ted
b
y
m
ea
n
s
o
f
San
g
er
's
f
u
ll
g
e
n
e
s
eq
u
e
n
ci
n
g
,
w
h
ic
h
i
s
p
er
f
o
r
m
ed
b
y
d
ir
ec
t
s
eq
u
en
ci
n
g
m
et
h
o
d
o
lo
g
y
.
T
h
e
d
ir
ec
t
s
eq
u
en
cin
g
an
al
y
s
is
is
co
n
s
id
er
ed
to
b
e
lab
o
r
io
u
s
,
e
x
p
en
s
iv
e
a
n
d
ti
m
e
-
co
n
s
u
m
i
n
g
[
1
8
,
1
9
]
.
P
C
R
is
n
o
w
a
co
m
m
o
n
a
n
d
o
f
te
n
in
d
i
s
p
en
s
ab
le
tech
n
iq
u
e
u
s
ed
in
m
ed
ical
a
n
d
b
io
lo
g
ical
r
esea
r
ch
lab
s
in
t
h
e
d
iag
n
o
s
is
o
f
h
er
ed
it
ar
y
d
i
s
ea
s
es [
2
0
,
2
1
]
.
T
h
e
lab
o
r
ato
r
y
m
et
h
o
d
s
ar
e
f
ac
in
g
c
h
alle
n
g
e
s
in
an
a
l
y
zi
n
g
t
h
e
g
e
n
e
s
eq
u
e
n
ce
s
to
d
etec
t
th
e
g
e
n
etic
d
is
o
r
d
er
.
T
h
er
ef
o
r
e,
th
e
p
r
o
ce
s
s
s
h
o
u
ld
b
e
au
to
m
ated
t
h
r
o
u
g
h
th
e
co
m
p
u
tatio
n
al
m
eth
o
d
s
an
d
d
is
ea
s
e
s
h
o
u
ld
b
e
id
en
tif
ied
ef
f
icie
n
tl
y
.
C
las
s
i
f
icatio
n
o
f
Facio
s
ca
p
u
lo
h
u
m
er
al
m
u
s
cu
lar
d
y
s
tr
o
p
h
y
(
FS
HD)
d
is
ea
s
e
is
d
o
n
e
b
y
m
o
n
ito
r
in
g
o
f
ex
p
r
ess
io
n
le
v
els.
Us
u
all
y
,
m
i
cr
o
ar
r
ay
g
en
e
ex
p
r
es
s
io
n
a
n
al
y
s
i
s
i
s
m
ai
n
l
y
f
o
cu
s
ed
to
ca
n
ce
r
d
is
ea
s
es.
I
n
t
h
e
p
ap
er
[
2
2
]
,
th
e
au
th
o
r
s
p
r
o
p
o
s
ed
an
ap
p
r
o
ac
h
to
class
if
y
in
g
t
h
e
t
y
p
es
o
f
Facio
s
ca
p
u
l
o
h
u
m
er
al
m
u
s
c
u
lar
d
y
s
tr
o
p
h
y
(
F
SHD)
.
A
m
o
d
el
i
s
cr
ea
ted
u
s
i
n
g
S
u
p
p
o
r
t v
ec
to
r
m
ac
h
i
n
e
to
clas
s
i
f
y
t
h
e
t
y
p
e
s
o
f
FS
HD.
T
h
e
au
th
o
r
s
C
at
h
er
i
n
e
T
.
Falk
,
J
am
e
s
M.
Gilc
h
r
is
t
[
2
3
]
d
ev
elo
p
ed
a
m
o
d
el
u
s
i
n
g
n
e
u
r
al
n
et
w
o
r
k
s
t
o
id
en
ti
f
y
w
h
eth
er
th
e
p
atie
n
t
is
af
f
ec
ted
f
r
o
m
L
i
m
b
Gr
id
d
le
m
u
s
c
u
lar
d
y
s
tr
o
p
h
y
(
L
GM
D)
.
T
h
e
d
ata
b
ased
o
n
th
e
p
atien
t
s
’
f
a
m
il
y
d
etail
s
ar
e
co
llected
.
T
h
e
class
if
icatio
n
o
f
d
is
ea
s
e
s
tat
u
s
i
s
m
ad
e
u
s
in
g
th
e
n
e
u
r
al
n
et
w
o
r
k
an
d
ac
h
ie
v
ed
an
ac
cu
r
ac
y
o
f
9
8
%.
T
h
e
au
th
o
r
s
in
[
2
4
]
co
n
s
tr
u
cted
a
p
r
o
tein
–
p
r
o
tein
in
ter
ac
tio
n
n
et
w
o
r
k
to
class
i
f
y
t
h
e
s
u
b
ty
p
es
o
f
m
u
s
c
u
lar
d
y
s
tr
o
p
h
y
t
h
r
o
u
g
h
m
ac
h
in
e
lear
n
in
g
tech
n
iq
u
e
s
.
Mic
r
o
ar
r
ay
g
e
n
e
ex
p
r
ess
io
n
d
atasets
ar
e
an
al
y
ze
d
an
d
th
e
p
r
o
tein
d
ata
a
n
d
th
e
i
r
in
ter
ac
tio
n
d
ata
ar
e
co
llected
an
d
a
n
et
w
o
r
k
is
co
n
s
tr
u
cted
to
class
i
f
y
th
e
s
u
b
t
y
p
es.
M
u
lti
cla
s
s
s
u
p
p
o
r
t
v
ec
to
r
m
ac
h
i
n
e
is
ap
p
lie
d
f
o
r
th
e
clas
s
i
f
icatio
n
o
f
s
ix
s
u
b
-
t
y
p
e
s
o
f
m
u
s
c
u
lar
d
y
s
tr
o
p
h
y
.
So
m
e
o
f
t
h
e
l
i
m
itatio
n
s
o
f
m
icr
o
ar
r
a
y
d
ata
to
clas
s
i
f
y
a
ll
f
o
r
m
s
o
f
m
u
s
c
u
lar
d
y
s
tr
o
p
h
y
ar
e
th
e
cDN
A
p
r
o
b
es
p
lo
tted
o
n
th
e
m
icr
o
ar
r
a
y
s
d
o
n
o
t
co
v
er
al
l
o
f
t
h
e
g
en
e
s
e
x
p
r
ess
ed
i
n
s
k
eleta
l
m
u
s
cle,
th
e
p
r
o
p
er
ties
o
f
p
r
o
b
e
cDN
A
s
h
a
v
e
n
o
t
b
ee
n
n
o
t
w
ell
-
c
h
ar
ac
ter
ized
,
h
o
m
o
lo
g
o
u
s
g
e
n
es
o
f
ea
ch
tar
g
et
g
en
e
m
a
y
cr
o
s
s
-
h
y
b
r
id
ize
w
it
h
t
h
e
p
r
o
b
es
an
d
b
ec
au
s
e
r
elativ
e
l
y
lar
g
e
a
m
o
u
n
ts
o
f
R
N
A
ar
e
r
eq
u
ir
ed
,
ea
ch
m
icr
o
ar
r
a
y
an
al
y
s
is
h
as r
eq
u
ir
ed
p
o
o
led
R
NA
s
a
m
p
le
s
f
r
o
m
s
ev
er
al
p
ati
en
ts
[
2
5
,
2
6
]
.
T
h
e
au
th
o
r
s
in
[
2
7
]
p
r
o
p
o
s
ed
a
m
o
d
el
to
class
i
f
y
t
h
e
t
y
p
e
s
o
f
Hu
m
a
n
L
eu
k
o
c
y
te
A
n
t
ig
en
(
HL
A)
g
en
e
in
to
d
if
f
er
en
t
f
u
n
ctio
n
a
l
g
r
o
u
p
s
b
y
ch
o
o
s
i
n
g
t
h
e
co
d
o
n
u
s
a
g
e
b
ias
as i
n
p
u
t.
I
n
th
eir
wo
r
k
,
th
e
y
co
n
v
er
ted
th
e
g
en
e
s
eq
u
en
ce
in
to
5
9
v
e
cto
r
ele
m
e
n
ts
b
y
ca
lc
u
lati
n
g
t
h
e
R
S
C
U
v
al
u
es
f
o
r
t
h
e
g
en
e
s
eq
u
e
n
ce
.
A
m
o
d
el
w
a
s
cr
ea
ted
u
s
i
n
g
Su
p
p
o
r
t v
ec
to
r
m
a
c
h
i
n
e
an
d
ac
h
iev
ed
an
a
cc
u
r
ac
y
r
ate
o
f
9
9
.
3
p
er
ce
n
t.
T
h
e
au
th
o
r
s
C
.
M.
Nis
h
a,
B
h
a
s
k
er
P
an
t,
an
d
K.
R
.
P
ar
d
asan
i
p
r
o
p
o
s
ed
an
ap
p
r
o
ac
h
b
ased
o
n
co
d
o
n
u
s
a
g
e
p
atter
n
to
cla
s
s
i
f
y
t
h
e
t
y
p
e
o
f
Hep
atiti
s
C
v
ir
u
s
(
HC
V)
t
h
at
ar
e
th
e
p
r
i
m
ar
y
r
ea
s
o
n
f
o
r
th
e
li
v
er
in
f
ec
t
io
n
.
T
o
class
if
y
th
e
s
u
b
class
o
f
it
s
g
e
n
o
t
y
p
e
a
m
o
d
el
w
as
cr
ea
ted
u
s
in
g
co
d
o
n
u
s
a
g
e
b
ias
as
in
p
u
t
to
m
u
lti cla
s
s
SVM
[
2
8
]
.
T
h
e
class
if
icat
io
n
o
f
m
u
s
cu
lar
d
y
s
tr
o
p
h
y
co
n
ti
n
u
es
to
ev
o
lv
e
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Evaluation Warning : The document was created with Spire.PDF for Python.
I
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N
:
2
2
5
2
-
8938
IJ
-
AI
Vo
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6
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4
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176
en
tire
m
u
tatio
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al
s
p
ec
tr
u
m
in
a
s
i
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g
le
p
lat
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m
.
Ho
w
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v
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,
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is
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s
s
e
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tial
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lo
o
k
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to
t
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ac
cu
r
ate
m
u
tatio
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ite
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ed
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th
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d
is
ea
s
e.
I
n
t
h
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ab
o
v
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m
e
n
tio
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ed
liter
at
u
r
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t
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clas
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l
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m
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w
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etails.
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s
y
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m
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s
v
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R
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C
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v
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n
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ated
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ce
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ith
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o
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n
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cleo
tid
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v
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ts
.
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n
th
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s
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ch
w
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k
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tu
r
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ated
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w
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g
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eq
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t.
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r
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ab
o
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t
m
is
s
en
s
e,
n
o
n
-
s
e
n
s
e
m
u
tatio
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d
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ile
n
t
m
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s
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tif
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d
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ated
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s
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n
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p
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tec
h
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iq
u
e.
2.
RE
S
E
ARCH
M
E
T
H
O
D
T
h
e
g
en
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s
eq
u
e
n
ce
s
a
n
d
it
s
p
atter
n
v
ar
y
i
n
e
v
er
y
h
u
m
an
.
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l
s
o
th
e
p
atter
n
g
ets
alt
er
ed
w
h
e
n
m
u
tatio
n
s
o
cc
u
r
in
t
h
e
c
h
r
o
m
o
s
o
m
e.
T
h
e
p
r
in
cip
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f
o
c
u
s
o
f
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i
s
r
esear
c
h
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s
to
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ti
f
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d
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cr
i
m
i
n
ati
v
e
f
ea
tu
r
e
s
an
d
to
p
r
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an
ef
f
icie
n
t
m
ac
h
in
e
lear
n
in
g
s
o
lu
tio
n
f
o
r
p
r
ed
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g
t
h
e
t
y
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e
o
f
m
u
s
c
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la
r
d
y
s
tr
o
p
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d
is
ea
s
e
w
it
h
t
h
e
s
ile
n
t
m
u
ta
tio
n
s
.
M
u
lti
-
cla
s
s
cla
s
s
i
f
icatio
n
is
f
o
r
m
u
lated
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r
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u
g
h
d
ata
m
o
d
elin
g
o
f
g
en
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s
eq
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e
n
ce
s
.
T
h
e
s
y
n
t
h
etic
m
u
tatio
n
al
g
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n
e
s
eq
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ce
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ar
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g
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ated
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h
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ea
s
ed
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en
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s
eq
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n
ce
s
ar
e
n
o
t
r
ea
d
il
y
av
ailab
le
f
o
r
th
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co
m
p
licated
d
is
ea
s
e.
Fi
v
e
t
y
p
es
o
f
m
u
s
c
u
l
ar
d
y
s
tr
o
p
h
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n
a
m
el
y
DM
D,
B
MD
,
E
MD
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L
GM
D
an
d
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MT
h
av
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co
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o
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u
ild
in
g
t
h
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d
is
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s
e
p
r
ed
ictio
n
m
o
d
el.
2
.
1
.
Dis
ea
s
e
I
dentif
ica
t
io
n M
o
del
T
h
e
Mu
s
c
u
lar
d
y
s
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o
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is
e
ase
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d
en
ti
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icatio
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m
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co
m
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r
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o
f
f
iv
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p
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ase
s
s
u
c
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u
tatio
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a
l
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eq
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ce
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n
er
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e
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r
e
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tr
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,
b
u
id
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g
t
h
e
m
o
d
el
a
n
d
clas
s
i
f
icatio
n
.
T
h
e
f
r
a
m
e
w
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k
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f
t
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p
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p
o
s
ed
m
o
d
el
is
ill
u
s
tr
ated
in
Fi
g
u
r
e
1.
Fig
u
r
e
1.
Dis
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s
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I
d
en
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f
icatio
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Mo
d
el
2
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.
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ize
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ased
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ch
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t
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ai
t.
T
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Evaluation Warning : The document was created with Spire.PDF for Python.
IJ
-
AI
IS
SN:
2252
-
8938
I
d
en
tifi
ca
tio
n
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Gen
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Dis
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V
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(
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177
g
en
e
to
d
iag
n
o
s
e
DM
D
a
n
d
h
en
ce
t
h
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s
a
m
e
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p
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e
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ate
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en
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en
co
d
in
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all
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h
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r
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ir
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es.
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tated
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n
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eq
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ated
b
y
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s
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p
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ased
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m
u
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its
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ch
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e.
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h
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i
n
f
o
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m
atio
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t
h
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p
o
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m
u
tatio
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i
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t
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ailab
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in
HGM
D1
(
Hu
m
a
n
Ge
n
e
M
u
tatio
n
Data
b
ase)
[
2
8
]
is
a
co
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ata
o
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er
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m
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r
e
f
er
en
ce
s
eq
u
en
ce
ar
e
f
ir
s
t
s
to
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ed
as
te
x
t
f
il
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s
.
U
s
in
g
th
e
Stri
n
g
r
ep
lace
(
)
f
u
n
ctio
n
f
r
o
m
t
h
e
s
tr
i
n
g
i
lib
r
ar
y
t
h
e
r
e
q
u
ir
ed
p
o
s
itio
n
i
s
to
b
e
alter
e
d
is
id
en
t
if
ied
an
d
r
ep
lace
d
w
it
h
th
e
n
u
cleo
tid
e
s
p
ec
if
ied
in
t
h
e
n
u
cleo
tid
e
ch
an
g
e
co
l
u
m
n
o
f
HGM
D
d
atab
ase.
Fiv
e
t
y
p
es
o
f
m
u
ta
tio
n
s
h
a
v
e
b
ee
n
co
n
s
id
er
ed
fo
r
g
en
er
ated
f
o
r
g
en
er
ati
n
g
m
u
tated
s
eq
u
e
n
ce
s
.
Usi
n
g
th
e
tr
ad
itio
n
al
p
o
s
itio
n
al
clo
n
in
g
ap
p
r
o
ac
h
th
e
m
u
tated
s
eq
u
e
n
ce
s
ar
e
g
en
er
a
ted
an
d
s
to
r
ed
as
f
as
ta
f
iles
.
C
o
n
s
id
er
th
e
m
i
s
s
e
n
s
e
m
u
tatio
n
al
i
n
f
o
r
m
atio
n
f
o
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th
e
E
MD
p
h
en
o
t
y
p
e
f
r
o
m
th
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E
m
er
i
n
g
e
n
e
s
u
c
h
as
n
u
cl
eo
tid
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ch
an
g
e
is
2
T
>C
w
h
i
ch
in
d
icate
s
i
n
th
e
p
o
s
itio
n
2
th
e
n
u
cleo
tid
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ch
a
n
g
es
f
r
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m
T
to
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alter
s
th
e
p
r
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tein
f
r
o
m
Me
t to
th
r
.
2
.
3
Dis
ea
s
e
G
ene
Da
t
a
s
et
s
T
h
e
g
en
e
s
a
s
s
o
ciate
d
w
i
th
d
is
ea
s
es
ar
e
ex
a
m
i
n
ed
.
T
h
er
e
a
r
e
ab
o
u
t
f
if
t
y
f
i
v
e
g
e
n
es
ev
ac
u
ated
w
it
h
fi
v
e
t
y
p
e
o
f
m
u
s
cu
lar
d
y
s
tr
o
p
h
y
.
T
ab
le
1
s
u
m
m
ar
ize
s
g
e
n
es
as
s
o
ciate
d
w
i
th
t
h
e
d
is
ea
s
e.
T
h
e
m
u
tatio
n
al
in
f
o
r
m
atio
n
is
r
etr
iev
ed
f
r
o
m
th
e
HGM
D
d
atab
ase
u
s
in
g
t
h
e
g
e
n
e
i
n
f
o
r
m
atio
n
f
o
r
th
e
r
eq
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ir
ed
p
h
en
o
t
y
p
e.
T
h
e
co
r
p
u
s
o
f
d
ata
h
o
ld
s
all
t
y
p
es
o
f
m
u
tated
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eq
u
e
n
c
es
s
u
c
h
as
Mi
s
s
e
n
s
e,
No
n
s
en
s
e,
s
y
n
o
n
y
m
o
u
s
,
I
n
s
er
tio
n
an
d
d
eletio
n
m
u
tatio
n
s
.
A
s
et
o
f
3
0
m
u
tated
g
e
n
e
s
eq
u
en
c
es
f
o
r
ea
ch
d
is
ea
s
e
i
s
g
e
n
er
a
ted
f
o
r
all
t
y
p
e
o
f
p
h
en
o
t
y
p
e
s
.
T
h
e
d
ataset
co
m
p
r
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s
es
o
f
1
5
0
m
u
tated
g
e
n
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s
eq
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ce
s
co
m
b
i
n
i
n
g
all
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o
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m
s
o
f
m
u
s
c
u
lar
d
y
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tr
o
p
h
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s
d
ev
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p
ed
.
T
ab
le
1
.
Gen
es a
s
s
o
ciate
d
w
it
h
d
if
f
er
en
t t
y
p
e
o
f
m
u
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lar
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y
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tr
o
p
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u
s
c
u
l
a
r
d
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st
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p
h
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se
a
se
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e
n
e
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sso
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t
e
d
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h
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d
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se
a
se
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n
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sc
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ss mu
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r
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A
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V
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Y
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K
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M
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O
M
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O
M
T
1
,
P
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M
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2
,
S
G
C
A
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B
,
S
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C
D
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G
C
G
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T
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M
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2
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T
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h
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r
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se
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J
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M
N
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R
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M
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M
E
D
2
5
,
M
F
N
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P
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3
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4
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Y
A
R
S
2
.4
.
F
e
a
t
ure
E
x
t
ra
ct
io
n a
nd
T
ra
ini
ng
D
a
t
a
s
et
C
h
a
n
g
e
in
th
e
s
tr
u
ctu
r
e
o
f
s
eq
u
en
ce
i
m
p
lie
s
t
h
e
ca
u
s
e
o
f
th
e
d
is
ea
s
e.
T
h
ese
s
t
r
u
ct
u
r
al
ch
a
n
g
es c
a
n
b
e
ca
p
tu
r
ed
as
f
ea
t
u
r
es
f
o
r
m
u
ta
tio
n
al
s
eq
u
e
n
ce
to
lear
n
th
e
p
r
ed
ictio
n
m
o
d
el.
T
h
e
co
d
o
n
u
s
a
g
e
p
atter
n
s
ar
e
co
n
s
id
er
ed
as
th
e
co
n
tr
ib
u
ti
n
g
f
ea
tu
r
es
f
o
r
r
ep
r
esen
tin
g
s
ile
n
t
m
u
tatio
n
s
in
t
h
e
m
u
tated
g
e
n
e
s
eq
u
en
ce
s
.
Sin
ce
co
d
o
n
u
s
ag
e
p
att
er
n
s
ar
e
d
iv
e
r
s
e
in
d
if
f
er
e
n
t
g
e
n
e
f
a
m
ilies
,
th
is
f
ea
t
u
r
e
in
p
u
t
is
a
w
e
ll
-
c
h
o
s
en
d
escr
ip
to
r
s
f
o
r
s
p
ec
if
y
in
g
d
if
f
er
en
t
g
en
e
f
a
m
ilie
s
f
o
r
all
t
y
p
es
o
f
d
is
ea
s
es.
E
ig
h
t
y
eig
h
t
ev
o
ca
ti
v
e
f
e
atu
r
es
f
o
r
b
o
th
th
e
s
y
n
o
n
y
m
o
u
s
a
n
d
n
o
n
s
y
n
o
n
y
m
o
u
s
m
u
tatio
n
s
ar
e
ex
tr
ac
te
d
an
d
f
ea
t
u
r
e
v
ec
to
r
s
ar
e
cr
ea
ted
f
o
r
lear
n
in
g
d
is
ea
s
e
p
r
ed
ictio
n
m
o
d
el.
2
.5
.
F
e
a
t
ures o
f
M
is
s
ens
e
a
nd
No
ns
en
s
e
M
uta
t
i
o
ns
T
h
e
m
is
s
en
s
e
a
n
d
n
o
n
s
e
n
s
e
m
u
tatio
n
a
l
f
ea
tu
r
e
s
ar
e
b
ased
o
n
a
n
n
o
tatio
n
,
s
tr
u
ct
u
r
e
an
d
ali
g
n
m
e
n
t
o
f
th
e
d
is
ea
s
ed
g
e
n
e
s
eq
u
e
n
ce
s
.
T
h
ey
ar
e
Gen
eI
D,
Gen
e
s
y
m
b
o
l,
C
h
r
o
m
o
s
o
m
e
n
u
m
b
er
,
Alte
r
atio
n
t
y
p
e,
P
r
o
tein
ch
an
g
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,
R
e
f
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allele,
Ob
s
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v
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allele,
Mu
tat
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p
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s
itio
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,
L
en
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t
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t
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s
eq
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n
ce
,
Mu
tat
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s
tar
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p
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itio
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,
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ta
tio
n
e
n
d
p
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n
,
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o
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o
f
m
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in
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h
e
r
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er
en
ce
a
llele
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s
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h
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t
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t
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t
in
t
h
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d
th
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ti
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ied
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th
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l
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h
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t
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th
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it
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to
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r
e
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ac
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ased
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tio
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o
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o
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k
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h
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h
o
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th
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s
eq
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ce
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s
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p
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eter
m
i
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ed
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h
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t
t
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ase
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lated
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th
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t c
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atter
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ig
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t
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m
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t
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alig
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t
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Qu
alit
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b
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er
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Evaluation Warning : The document was created with Spire.PDF for Python.
IJ
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SN:
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3.
RE
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IJ
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181
4.
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Evaluation Warning : The document was created with Spire.PDF for Python.
I
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2
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8938
IJ
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6
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D
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ee
Evaluation Warning : The document was created with Spire.PDF for Python.
IJ
-
AI
IS
SN:
2252
-
8938
I
d
en
tifi
ca
tio
n
o
f
R
a
r
e
Gen
etic
Dis
o
r
d
er fr
o
m
S
in
g
le
N
u
cleo
ti
d
e
V
a
r
ia
n
ts
.
.
.
(
S
a
th
ya
vika
s
in
i K
)
183
A
l
s
o
t
h
e
p
r
ed
ictio
n
m
o
d
el
i
s
m
o
r
e
e
f
f
ec
tiv
e
an
d
r
eliab
le
s
in
ce
it
i
s
g
e
n
er
ated
b
ased
o
n
i
n
telli
g
e
n
t
h
i
n
ts
co
llected
f
r
o
m
m
u
t
ated
g
e
n
e
s
eq
u
en
ce
s
.
5.
CO
NCLU
SI
O
N
Mu
s
c
u
lar
d
y
s
tr
o
p
h
y
d
is
ea
s
e
i
d
en
tific
atio
n
w
o
r
k
i
s
t
h
e
p
r
o
b
le
m
o
f
lear
n
i
n
g
m
u
lticla
s
s
cla
s
s
i
f
icatio
n
s
y
s
te
m
th
a
t
ca
n
s
u
its
in
b
io
in
f
o
r
m
atic
s
en
v
ir
o
n
m
e
n
t
to
i
d
en
tify
t
h
e
d
is
ea
s
e
e
f
f
ec
tiv
e
l
y
.
C
u
r
r
en
tl
y
,
t
h
is
p
r
o
b
lem
h
as
n
o
t
b
e
en
b
r
o
a
d
ly
s
tu
d
ied
in
th
e
liter
at
u
r
e,
an
d
ex
is
t
in
g
ap
p
r
o
ac
h
es
ar
e
eith
er
r
estricte
d
to
a
s
m
all
n
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m
b
er
o
f
clas
s
es
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e
to
co
m
p
u
tatio
n
al
is
s
u
e
s
o
r
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n
s
u
f
f
icie
n
t
d
ata.
T
h
e
p
r
o
p
o
s
ed
m
o
d
el
r
elies
o
n
t
w
o
m
ai
n
id
ea
s
.
T
h
e
f
ir
s
t id
ea
is
to
d
esi
g
n
t
h
e
d
is
cr
i
m
in
at
iv
e
f
ea
t
u
r
es
f
r
o
m
t
h
e
m
u
tated
g
e
n
e
s
eq
u
en
c
es to
b
u
ild
a
m
o
d
el
f
o
r
id
en
ti
f
y
in
g
t
h
e
t
y
p
e
o
f
th
e
g
en
et
ic
d
is
o
r
d
er
.
T
h
e
s
ec
o
n
d
id
ea
is
to
ca
p
tu
r
e
s
y
n
o
n
y
m
o
u
s
a
n
d
n
o
n
–
s
y
n
o
n
y
m
o
u
s
SNV
’
s
f
r
o
m
t
h
e
g
e
n
er
ated
s
eq
u
e
n
ce
s
an
d
to
class
i
f
y
t
h
e
t
y
p
e
o
f
d
is
ea
s
e.
T
h
e
ex
p
er
i
m
en
t
s
l
ed
o
n
th
e
d
is
ea
s
ed
g
en
e
s
eq
u
en
ce
s
an
d
as
s
ess
ed
w
it
h
ev
al
u
atio
n
m
et
h
o
d
o
n
th
e
m
o
d
el
b
u
ilt,
s
h
o
w
t
h
at
o
u
r
m
et
h
o
d
is
v
al
u
ab
le
th
a
n
e
x
i
s
tin
g
d
i
s
ea
s
e
id
e
n
ti
f
icatio
n
p
r
o
ce
d
u
r
es
w
i
th
r
esp
ec
t
to
s
i
g
n
i
f
ica
n
t
f
ea
t
u
r
es
.
Fu
r
t
h
er
m
o
r
e,
w
h
e
n
t
h
e
s
u
p
er
v
is
ed
lear
n
in
g
al
g
o
r
ith
m
s
ar
e
ap
p
lied
th
e
d
ec
is
io
n
tr
ee
cla
s
s
i
f
ier
o
u
tp
er
f
o
r
m
s
o
th
er
alg
o
r
it
h
m
s
i
n
p
r
ed
ictio
n
.
As
t
h
e
n
atu
r
e
o
f
t
h
e
ap
p
licat
io
n
d
e
m
a
n
d
s
i
n
m
o
r
e
ac
cu
r
ate
d
is
ea
s
e
p
r
ed
ictio
n
th
r
o
u
g
h
m
u
tated
g
e
n
e
s
eq
u
e
n
ce
s
,
it
i
s
f
o
u
n
d
t
h
at
ap
p
l
y
i
n
g
t
h
e
e
x
tr
ac
ted
f
ea
t
u
r
es
i
n
m
ac
h
in
e
lear
n
in
g
ap
p
r
o
ac
h
is
s
ig
n
if
ican
t to
id
en
tify
th
e
t
y
p
e
o
f
m
u
s
cu
lar
d
y
s
tr
o
p
h
y
d
is
ea
s
e.
RE
F
E
R
E
NC
E
S
[1
]
In
u
sh
a
P
a
n
ig
ra
h
i,
Ba
lraj
M
i
tt
a
l
,
“
Ca
rrier
De
tec
ti
o
n
a
n
d
P
re
n
a
tal
Dia
g
n
o
sis
in
Du
c
h
e
n
n
e
/Be
c
k
e
r
M
u
sc
u
lar
D
y
stro
p
h
y
”
,
In
d
ian
P
e
d
iatrics
2
0
0
1
;
3
8
:
6
3
1
-
6
3
9
.
[2
]
Le
ig
h
B.
W
a
d
d
e
ll
,
e
t.
a
l,
"
Dia
g
n
o
sis
o
f
th
e
M
u
sc
u
lar
Dy
stro
p
h
ies
"
In
stit
u
te
f
o
r
Ne
u
r
o
sc
ien
c
e
a
n
d
M
u
sc
le
Re
se
a
rc
h
,
Ch
il
d
re
n
’s Ho
sp
i
tal
a
t
W
e
st
m
e
a
d
a
n
d
Disc
ip
li
n
e
o
f
P
a
e
d
iatrics
&
C
h
il
d
He
a
lt
h
,
Un
iv
e
rsit
y
o
f
s
y
d
n
e
y
,
A
u
stra
li
a
.
[3
]
L
e
n
k
a
F
a
jk
u
so
v
a
,
Zd
e
n
e
Ik
L
u
k
a
sIb
,
M
iro
sla
v
a
Tv
rd
o
a
k
o
v
a
a
,
V
iera
Ku
h
ro
v
a
a
,
Jirio
a
Ha
a
jek
b
,
Jirio
a
F
a
jk
u
sc
,
No
v
e
l
d
y
stro
p
h
in
m
u
tatio
n
s
re
v
e
a
led
b
y
a
n
a
l
y
sis
o
f
d
y
stro
p
h
in
m
RNA
:
a
lt
e
rn
a
ti
v
e
sp
li
c
in
g
su
p
p
re
ss
e
s
th
e
p
h
e
n
o
ty
p
ic effe
c
t
o
f
a
n
o
n
se
n
se
m
u
tatio
n
Ne
u
ro
m
u
sc
u
lar Diso
rd
e
rs 1
1
(
2
0
0
1
)
.
[4
]
Ke
v
in
M
.
F
lan
ig
a
n
,
M
.
D
.
T
h
e
M
u
sc
u
lar
Dy
stro
p
h
ies
,
T
h
iem
e
M
e
d
ica
l
P
u
b
li
s
h
e
rs
IS
S
N
0
2
7
1
-
8
2
3
5
S
e
m
in
a
rs
in
Ne
u
ro
lo
g
y
V
o
l.
3
2
No
.
3
/
2
0
1
2
.
[5
]
Zu
b
rz
y
c
k
a
-
G
a
a
rn
EE
,
Bu
lm
a
n
D
E,
Ka
rp
a
ti
G
,
e
t
a
l.
T
h
e
Du
c
h
e
n
n
e
m
u
sc
u
lar
d
y
stro
p
h
y
g
e
n
e
p
ro
d
u
c
t
is
lo
c
a
li
z
e
d
i
n
sa
rc
o
le
m
m
a
o
f
h
u
m
a
n
sk
e
leta
l
m
u
sc
le.
Na
tu
re
1
9
8
8
;3
3
3
(
6
1
7
2
):
4
6
6
±4
6
9
.
[6
]
Ka
th
a
rin
e
Bu
sh
b
y
,
e
t.
a
l,
"
Dia
g
n
o
sis
a
n
d
m
a
n
a
g
e
m
e
n
t
o
f
Du
c
h
e
n
n
e
m
u
sc
u
lar
d
y
stro
p
h
y
,
p
a
rt
1
:
d
iag
n
o
sis,
a
n
d
p
h
a
rm
a
c
o
lo
g
ica
l
a
n
d
p
sy
c
h
o
so
c
ial
m
a
n
a
g
e
m
e
n
t"
T
h
e
Lan
c
e
t
,
No
v
e
m
b
e
r
3
0
,
2
0
0
9
DO
I:1
0
.
1
0
1
6
/S
1
4
7
4
-
4
4
2
2
(
0
9
)
7
0
2
7
1
-
6
.
[7
]
A
n
n
e
He
lb
li
n
g
-
L
e
c
lerc
,
G
ise
Á
l
e
Bo
n
n
e
,
a
n
d
Ke
tt
y
S
c
h
w
a
rtz,
"
Em
e
r
y
-
Dre
i
f
u
ss
m
u
sc
u
lar
d
y
stro
p
h
y
"
Eu
ro
p
e
a
n
J
o
u
rn
a
l
o
f
Hu
ma
n
Ge
n
e
ti
c
s
(
2
0
0
2
)
.
[8
]
M
a
W
J1
,
Ha
sh
ii
M
,
e
t.
a
l,
"
No
n
-
s
y
n
o
n
y
m
o
u
s
sin
g
le
-
n
u
c
leo
ti
d
e
v
a
riatio
n
s
o
f
th
e
h
u
m
a
n
o
x
y
to
c
in
re
c
e
p
to
r
g
e
n
e
a
n
d
a
u
ti
sm
sp
e
c
tru
m
d
iso
rd
e
rs:
a
c
a
se
-
c
o
n
tro
l
stu
d
y
in
a
Ja
p
a
n
e
se
p
o
p
u
lati
o
n
a
n
d
f
u
n
c
ti
o
n
a
l
a
n
a
ly
sis
.
"
M
o
lec
u
lar
A
u
ti
s
m
,
2
0
1
3
.
[9
]
S
h
u
a
i
Zen
g
,
Ji
n
g
Ya
n
g
,
e
t.
a
l,
"
EF
IN:
p
re
d
icti
n
g
th
e
f
u
n
c
ti
o
n
a
l
im
p
a
c
t
o
f
n
o
n
sy
n
o
n
y
m
o
u
s
si
n
g
le
n
u
c
leo
ti
d
e
p
o
ly
m
o
rp
h
ism
s in
h
u
m
a
n
g
e
n
o
m
e
"
,
BM
C
G
e
n
o
m
i
c
s,
2
0
1
4
[1
0
]
h
tt
p
:
//
ww
w
.
n
c
b
i.
n
lm
.
n
ih
.
g
o
v
/b
o
o
k
s/NBK
2
1
5
7
8
[1
1
]
Ka
n
n
,
M
.
G
.
:
A
d
v
a
n
c
e
s
in
tran
sla
ti
o
n
a
l
b
io
in
f
o
rm
a
ti
c
s:
c
o
m
p
u
tatio
n
a
l
a
p
p
r
o
a
c
h
e
s
f
o
r
th
e
h
u
n
ti
n
g
o
f
d
ise
a
se
g
e
n
e
s.
Brief
in
g
s in
Bio
in
f
o
rm
a
ti
c
s 1
1
,
9
6
–
1
1
0
(2
0
0
9
)
.
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8
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9
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0
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Dr.M
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Dr.D
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Res
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2
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1
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1
]
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.
[2
2
]
F
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lez
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.
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