Seminars in Immunopathology,
Год журнала:
2021,
Номер
44(1), С. 137 - 147
Опубликована: Сен. 10, 2021
Genetic
studies,
including
genome-wide
association
have
identified
many
common
variants
that
are
associated
with
autoimmune
diseases.
Strikingly,
in
addition
to
being
frequently
observed
healthy
individuals,
a
number
of
these
shared
across
diseases
diverse
clinical
presentations.
This
highlights
the
potential
for
improved
disease
understanding
which
could
be
achieved
by
characterising
mechanism
lead
increased
risk
disease.
Of
particular
interest
is
identifying
novel
drug
targets
or
repositioning
drugs
currently
used
other
The
majority
do
not
alter
coding
regions
and
it
often
difficult
generate
plausible
hypothetical
affect
disease-relevant
genes
pathways.
Given
this
area,
considerable
effort
has
been
invested
developing
applying
appropriate
methodologies.
Two
most
important
technologies
space
include
both
low-
high-throughput
genomic
perturbation
using
CRISPR/Cas9
system
massively
parallel
reporter
assays.
In
review,
we
introduce
field
functional
genomics
use
numerous
examples
demonstrate
recent
future
impact
technologies.
Human Molecular Genetics,
Год журнала:
2020,
Номер
29(R1), С. R59 - R65
Опубликована: Май 15, 2020
Associations
between
genetic
loci
and
increased
susceptibility
to
autoimmune
disease
have
been
well
characterized,
however,
translating
this
knowledge
into
mechanistic
insight
patient
benefit
remains
a
challenge.
While
improvements
in
the
precision,
completeness
accuracy
of
our
understanding
diseases
will
undoubtedly
be
helpful,
meeting
challenge
require
two
interlinked
problems
addressed:
first
which
highly
correlated
variants
at
an
individual
locus
is
responsible
for
risk,
second
what
are
downstream
effects
variant.
Given
that
majority
thought
affect
non-coding
regulatory
elements,
question
often
reframed
as
target
gene(s)
pathways
affected
by
causal
variants.
Currently,
these
questions
being
addressed
using
wide
variety
novel
techniques
datasets.
In
many
cases,
approaches
complementary
it
likely
most
accurate
picture
generated
consolidating
information
relating
transcription,
activity,
chromatin
accessibility,
conformation
readouts
from
functional
experiments,
such
genome
editing
reporter
assays.
It
clear
necessary
gather
relevant
cell
types
conditions
doing
so
etiology
improved.
This
review
focused
on
field
genomics
with
particular
focus
exciting
significant
research
published
within
last
couple
years.
Disease Models & Mechanisms,
Год журнала:
2023,
Номер
16(3)
Опубликована: Март 1, 2023
ABSTRACT
Genome-wide
association
studies
have
identified
hundreds
of
genetic
loci
that
are
associated
with
immune-mediated
diseases.
Most
disease-associated
variants
non-coding,
and
a
large
proportion
these
lie
within
enhancers.
As
result,
there
is
pressing
need
to
understand
how
common
variation
might
affect
enhancer
function
thereby
contribute
(and
other)
In
this
Review,
we
first
describe
statistical
experimental
methods
identify
causal
modulate
gene
expression,
including
fine-mapping
massively
parallel
reporter
assays.
We
then
discuss
approaches
characterise
the
mechanisms
by
which
immune
function,
such
as
clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)-based
screens.
highlight
examples
that,
elucidating
effects
disease
enhancers,
provided
important
insights
into
uncovered
key
pathways
disease.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Май 7, 2023
Abstract
Increasing
global
rates
of
autoimmune
and
inflammatory
disease
present
a
burgeoning
threat
to
human
health
1
.
This
is
compounded
by
the
limited
efficacy
available
treatments
high
failure
during
drug
development
2
–
underscoring
an
urgent
need
better
understand
mechanisms.
Here
we
show
how
genetics
could
address
this
challenge.
By
investigating
intergenic
haplotype
on
chr21q22,
independently
linked
bowel
(IBD),
ankylosing
spondylitis,
primary
sclerosing
cholangitis
Takayasu’s
arteritis
3–6
,
discover
that
causal
gene,
ETS2
master
regulator
responses
in
macrophages
delineate
risk
increases
expression.
Genes
regulated
were
prominently
expressed
affected
tissues
from
chr21q22-associated
diseases
more
enriched
for
IBD
GWAS
hits
than
almost
all
previously
described
pathways.
Overexpressing
resting
produced
activated
effector
state
phenocopied
intestinal
7
with
upregulation
multiple
targets
including
TNFα
IL-23.
Using
database
cellular
signatures
8
identify
drugs
modulate
pathway
validate
potent
anti-inflammatory
activity
one
class
small
molecules
vitro
ex
vivo
Together,
highlights
potential
common
genetic
associations
improve
both
understanding
treatment
disease.
Genes,
Год журнала:
2020,
Номер
11(12), С. 1482 - 1482
Опубликована: Дек. 9, 2020
Immune-mediated
diseases
(IMDs)
are
complex
pathologies
that
strongly
influenced
by
environmental
and
genetic
factors.
Associations
between
loci
susceptibility
to
these
have
been
widely
studied,
hundreds
of
risk
variants
emerged
during
the
last
two
decades,
with
researchers
observing
a
shared
pattern
among
them.
Nevertheless,
pathological
mechanism
behind
associations
remains
challenge
has
just
started
be
understood
thanks
functional
genomic
approaches.
Transcriptomics,
regulatory
elements,
chromatin
interactome,
as
well
experimental
characterization
findings,
constitute
key
elements
in
emerging
understandings
how
genetics
affects
etiopathogenesis
IMDs.
In
this
review,
we
will
focus
on
latest
advances
field
genomics,
centering
our
attention
systemic
rheumatic
Seminars in Immunopathology,
Год журнала:
2021,
Номер
44(1), С. 137 - 147
Опубликована: Сен. 10, 2021
Genetic
studies,
including
genome-wide
association
have
identified
many
common
variants
that
are
associated
with
autoimmune
diseases.
Strikingly,
in
addition
to
being
frequently
observed
healthy
individuals,
a
number
of
these
shared
across
diseases
diverse
clinical
presentations.
This
highlights
the
potential
for
improved
disease
understanding
which
could
be
achieved
by
characterising
mechanism
lead
increased
risk
disease.
Of
particular
interest
is
identifying
novel
drug
targets
or
repositioning
drugs
currently
used
other
The
majority
do
not
alter
coding
regions
and
it
often
difficult
generate
plausible
hypothetical
affect
disease-relevant
genes
pathways.
Given
this
area,
considerable
effort
has
been
invested
developing
applying
appropriate
methodologies.
Two
most
important
technologies
space
include
both
low-
high-throughput
genomic
perturbation
using
CRISPR/Cas9
system
massively
parallel
reporter
assays.
In
review,
we
introduce
field
functional
genomics
use
numerous
examples
demonstrate
recent
future
impact
technologies.