PLoS Genetics,
Год журнала:
2024,
Номер
20(12), С. e1011502 - e1011502
Опубликована: Дек. 5, 2024
Primary
angle
closure
glaucoma
(PACG)
affects
more
than
20
million
people
worldwide,
with
an
increased
prevalence
in
south-east
Asia.
In
a
prior
haplotype-based
Genome
Wide
Association
Study
(GWAS),
we
identified
novel
CNTNAP5
genic
region,
significantly
associated
PACG.
the
current
study,
have
extended
our
perception
of
involvement
glaucomatous
neurodegeneration
zebrafish
model,
through
investigating
phenotypic
consequences
pertinent
to
retinal
degeneration
upon
knockdown
cntnap5
by
translation-blocking
morpholinos.
While
was
successfully
validated
using
antibody,
immunofluorescence
followed
western
blot
analyses
cntnap5-morphant
(MO)
revealed
expression
acetylated
tubulin
indicative
perturbed
cytoarchitecture
layers.
Moreover,
significant
loss
Nissl
substance
is
observed
neuro-retinal
layers
cntnap5-MO
eye,
indicating
neurodegeneration.
Additionally,
spontaneous
movement
behavioural
analysis,
lower
average
distance
traversed
light
phase
compared
mismatch-controls,
whereas
no
difference
dark
phase,
corroborating
vision
zebrafish.
This
study
provides
first
direct
functional
evidence
putative
role
visual
Journal of Clinical Medicine,
Год журнала:
2025,
Номер
14(2), С. 559 - 559
Опубликована: Янв. 16, 2025
Background/Objectives:
Age-related
macular
degeneration
(AMD)
is
a
global
cause
of
vision
loss,
with
limited
therapeutic
options
highlighting
the
need
for
effective
biomarkers.
This
study
aimed
to
characterize
plasma
DNA
methyltransferase
expression
(DNMT1,
DNMT3A,
and
DNMT3B)
in
AMD
patients
explore
divergent
patterns
across
different
stages
AMD.
Methods:
Thirty-eight
were
prospectively
enrolled
stratified
by
disease
severity:
eAMD,
iAMD,
nAMD,
aAMD.
Comprehensive
ophthalmological
assessments
performed,
including
best-corrected
visual
acuity,
digital
color
fundus
photographs,
Spectral
Domain
Optical
Coherence
Tomography.
Peripheral
blood
samples
collected
RNA
extraction
qRT-PCR
access
epigenetic
effectors’
transcriptional
expression,
namely
DNMT1,
DNMT3B
genes.
The
data
analyzed
using
IBM
SPSS
29.
Results:
DNMT1
was
significantly
downregulated
late
(−0.186
±
0.341)
compared
early/intermediate
(0.026
0.246).
Within
AMD,
aAMD
exhibited
marked
downregulation
(−0.375
0.047)
nAMD
(0.129
0.392).
DNMT3A
showed
similar
patterns,
correlating
stage.
Conclusions:
identified
stage-specific
differences
DNMT
emphasizing
its
potential
as
biomarker
progression
target
future
research
into
personalized
strategies.
Antioxidants,
Год журнала:
2024,
Номер
13(5), С. 539 - 539
Опубликована: Апрель 27, 2024
Oxidative
stress
forms
part
of
the
molecular
basis
contributing
to
development
and
manifestation
myopia,
a
refractive
error
with
associated
pathology
that
is
increasingly
prevalent
worldwide
subsequently
leads
an
upsurge
in
degenerative
visual
impairment
due
conditions
are
especially
high
myopia.
The
purpose
our
study
was
examine
interrelation
potential
oxidative-stress-related
metabolites
found
aqueous
humor
high-myopic,
low-myopic,
non-myopic
patients
within
clinical
study.
We
conducted
cross-sectional
study,
selecting
two
sets
undergoing
cataract
surgery.
first
set,
which
used
analyze
through
NMR
assay,
comprised
116
patients.
A
total
59
were
assigned
quantified.
PLS-DA
score
plot
clearly
showed
separation
minimal
overlap
between
HM
control
samples.
model
allowed
us
determine
31
major
metabolite
differences
groups.
Complementary
statistical
analysis
data
six
presented
significant
among
experimental
groups
(p
<
005).
number
these
discovered
have
direct
or
indirect
connection
oxidative
linked
myopic
eyes.
Notably,
we
identified
bioenergetic
pathways
undergone
methylation,
along
choline
its
derivatives.
second
set
consisted
73
who
underwent
glutathione
assay.
Here,
variations
both
reduced
oxidized
all
patient
0.01)
for
time.
Axial
length,
status,
complete
ophthalmologic
examination
also
recorded,
interrelations
metabolic
parameters
evaluated.
Trends in Genetics,
Год журнала:
2024,
Номер
unknown
Опубликована: Май 1, 2024
Intimate
links
between
epigenome
modifications
and
metabolites
allude
to
a
crucial
role
of
cellular
metabolism
in
transcriptional
regulation.
Retina,
being
highly
metabolic
tissue,
adapts
by
integrating
inputs
from
genetic,
epigenetic,
extracellular
signals.
Precise
global
epigenomic
signatures
guide
development
homeostasis
the
intricate
retinal
structure
function.
Epigenomic
realignment
are
hallmarks
aging
highlight
link
epigenome–metabolism
nexus
with
aging-associated
multifactorial
traits
affecting
retina,
including
age-related
macular
degeneration
glaucoma.
Here,
we
focus
on
emerging
principles
control
gene
regulation,
emphasis
their
contribution
human
disease.
In
addition,
discuss
potential
mitigation
strategies
involving
lifestyle
changes
that
target
epigenome-metabolome
relationship
for
maintaining
Journal of Biological Chemistry,
Год журнала:
2025,
Номер
unknown, С. 108267 - 108267
Опубликована: Фев. 1, 2025
Genome-wide
association
study
(GWAS)
and
quantitative
trait
locus
(QTL)
mapping
methods
provide
valuable
insights
opportunities
for
identifying
functional
gene
underlying
phenotype
formation.
However,
the
majority
of
GWAS
risk
loci
QTLs
located
in
non-coding
regions,
posing
significant
challenges
pinpointing
protein-coding
genes
associated
with
specific
traits.
Moreover,
growing
evidence
suggests
not
all
are
functional,
emphasizing
critical
need
prioritizing
causal
sites-a
task
paramount
importance
biologists.
The
accumulation
publicly
available
multi-omics
data
provides
an
unprecedented
opportunity
to
annotate
prioritize
QTLs.Therefore,
we
developed
a
comprehensive
database
encompassing
four
major
agricultural
species-pig,
sheep,
cattle,
chicken.
This
integrates
accessible
datasets,
including
140
studies
(covering
471
traits),
2,625
QTL
datasets
(spanning
1,235
86
Hi-C
(from
8
cell/tissue
types),
95
epigenomic
4
769
transcription
factor
motifs.
aims
link
GWAS/QTL
regions
target
they
regulate,
regulatory
elements.
Ultimately,
it
resource
potential
validation
targets
elucidating
molecular
pathways
economically
important
traits
animals.
Cell Genomics,
Год журнала:
2025,
Номер
5(2), С. 100773 - 100773
Опубликована: Фев. 1, 2025
In
this
issue
of
Cell
Genomics,
Choi
et
al.1
report
a
novel
approach,
privateQTL,
which
leverages
secure
multiparty
computation
(MPC)
to
enable
federated
expression
quantitative
trait
loci
(eQTL)
mapping
across
institutions
without
compromising
data
privacy.
Zhang
al.
preview
their
approach
and
discuss
its
application
in
future
genetic
analyses.
Human Molecular Genetics,
Год журнала:
2023,
Номер
unknown
Опубликована: Ноя. 2, 2023
Genome-wide
association
studies
have
contributed
extensively
to
the
discovery
of
disease-associated
common
variants.
However,
genetic
contribution
complex
traits
is
still
largely
difficult
interpret.
We
report
a
genome-wide
study
2394
cases
and
2393
controls
for
age-related
macular
degeneration
(AMD)
via
whole-genome
sequencing,
with
46.9
million
Our
reveals
significant
single-variant
signals
at
four
loci
independent
gene-based
in
CFH,
C2,
C3,
NRTN.
Using
data
from
Exome
Aggregation
Consortium
(ExAC)
test,
we
demonstrate
an
enrichment
predicted
rare
loss-of-function
variants
CFI,
as-yet
unreported
gene
AMD,
ORMDL2.
method
using
large
variant
list
without
individual-level
genotypes
as
external
reference
provides
flexible
convenient
approach
leverage
publicly
available
datasets
augment
search
associations,
which
can
explain
additional
disease
risk
AMD.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 29, 2024
Abstract
Most
genetic
risk
variants
linked
to
ocular
diseases
are
non-protein
coding
and
presumably
contribute
disease
through
dysregulation
of
gene
expression,
however,
deeper
understanding
their
mechanisms
action
has
been
impeded
by
an
incomplete
annotation
the
transcriptional
regulatory
elements
across
different
retinal
cell
types.
To
address
this
knowledge
gap,
we
carried
out
single-cell
multiomics
assays
investigate
chromatin
accessibility,
DNA
methylome
3D
architecture
in
human
retina,
macula,
pigment
epithelium
(RPE)/choroid.
We
identified
420,824
unique
candidate
characterized
states
23
sub-classes
cells.
Comparative
analysis
landscapes
between
mouse
retina
cells
further
revealed
both
evolutionarily
conserved
divergent
gene-regulatory
programs.
Leveraging
rapid
advancements
deep-learning
techniques,
developed
sequence-based
predictors
interpret
non-coding
diseases.
Our
study
establishes
retina-wide,
transcriptome,
epigenome,
genome
atlases,
provides
a
resource
for
studying
programs
relevant
