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Genetic dissection of the ity3 locus identifies a role for ncf2 co-expression modules and suggests selp as a candidate gene underlying the ity3.2 locus.
[typhoid]
Typhoid
fever
and
salmonellosis
,
which
are
caused
by
Salmonella
typhi
and
typhimurium
,
respectively
,
are
responsible
for
significant
morbidity
and
mortality
in
both
developed
and
developing
countries
.
We
model
typhoid
fever
using
mice
infected
with
Salmonella
typhimurium
,
which
results
in
a
systemic
disease
,
whereby
the
outcome
of
infection
is
variable
in
different
inbred
strains
of
mice
.
This
model
recapitulates
several
clinical
aspects
of
the
human
disease
and
allows
the
study
of
the
host
response
to
Salmonella
typhimurium
infection
in
vivo
.
Previous
work
in
our
laboratory
has
identified
three
loci
(
Ity
,
Ity
2
,
and
Ity
3
)
in
the
wild-derived
MOLF
/
Ei
mice
influencing
survival
after
infection
with
Salmonella
typhimurium
.
Fine
mapping
of
the
Ity
3
locus
indicated
that
two
sub-loci
contribute
collectively
to
the
susceptibility
of
B
6
.
MOLF-Ity
/
Ity
3
congenic
mice
to
Salmonella
infection
.
In
the
current
paper
,
we
provided
further
evidence
supporting
a
role
for
Ncf
2
(
neutrophil
cytosolic
factor
2
a
subunit
of
NADPH
oxidase
)
as
the
gene
underlying
the
Ity
3
.
1
sub-locus
.
Gene
expression
profiling
indicated
that
the
Ity
3
.
1
sub-locus
defined
a
global
gene
expression
signature
with
networks
articulated
around
Ncf
2
.
Furthermore
,
based
on
differential
expression
and
complementation
analysis
using
Selp
(
selectin-
P
)
knock-out
mice
,
Selp
was
identified
as
a
strong
candidate
gene
for
the
Ity
3
.
2
sub-locus
.
Diseases
Validation
Diseases presenting
"fever"
symptom
22q11.2 deletion syndrome
acute rheumatic fever
alexander disease
allergic bronchopulmonary aspergillosis
canavan disease
carcinoma of the gallbladder
child syndrome
congenital toxoplasmosis
cushing syndrome
cystinuria
dracunculiasis
erdheim-chester disease
esophageal adenocarcinoma
esophageal carcinoma
familial mediterranean fever
focal myositis
hodgkin lymphoma, classical
lamellar ichthyosis
legionellosis
locked-in syndrome
malignant atrophic papulosis
neonatal adrenoleukodystrophy
neuralgic amyotrophy
oculocutaneous albinism
papillon-lefèvre syndrome
pyomyositis
pyruvate dehydrogenase deficiency
scrub typhus
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
typhoid
waldenström macroglobulinemia
wolf-hirschhorn syndrome
This symptom has already been validated