Regulatory SVA retrotransposons and classical HLA genotyped-transcripts associated with Parkinson’s disease
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Март 25, 2024
Introduction
Parkinson’s
disease
(PD)
is
a
neurodegenerative
and
polygenic
disorder
characterised
by
the
progressive
loss
of
neural
dopamine
onset
movement
disorders.
We
previously
described
eight
SINE-VNTR-Alu
(SVA)
retrotransposon-insertion-polymorphisms
(RIPs)
located
expressed
within
Human
Leucocyte
Antigen
(HLA)
genomic
region
chromosome
6
that
modulate
differential
co-expression
71
different
genes
including
HLA
classical
class
I
II
in
Progression
Markers
Initiative
(PPMI)
cohort.
Aims
methods
In
present
study,
we
(1)
reanalysed
PPMI
transcriptomic
sequencing
data
obtained
from
whole
blood
1521
individuals
(867
cases
654
controls)
to
infer
genotypes
transcripts
as
well
DRA
DRB3/4/5
haplotypes,
(2)
examined
statistical
differences
between
three
PD
subgroups
(cases)
healthy
controls
(HC)
for
SVA
transcribed
inferred
haplotypes.
Results
Significant
57
alleles
(21
36
alleles)
up
three-field
resolution
four
were
detected
at
p<0.05
Fisher’s
exact
test
one
or
other
(750
with
PD,
prodromes,
60
who
had
scans
without
evidence
deficits
[SWEDD]),
when
compared
against
group
HCs
cohort
not
corrected
Bonferroni
multiple
comparisons.
Fourteen
20
significant
unique
PD-HC
comparison,
whereas
31
overlapped
two
more
subgroup
Only
HLA-DRA*01:01:01
-
DQA1*03:01:01
protective
(PD
v
HC),
-DQA1*03:03:01
risk
(HC
Prodrome)
allele
Prodrome),
-DRA*01:01:02
DRB4*01:03:02
(SWEDD
NR_SVA_381
genotype
HC)
5%
homozygous
insertion
frequency
near
HLA-DPA1
,
(
Pc<0.1
)
after
corrections.
The
homologous
significantly
decreased
transcription
levels
HLA-DPB1
its
presence
factor
Pc=0.012
PD.
most
frequent
haplotype
was
NR_SVA_381/DPA1*02/DPB1*01
(3.7%).
Although
C*07/B*07/DRB5*01/DRB1*15/DQB1*06
5-loci
phased-haplotype
(n,
76)
cohort,
only
six
them
(8%).
Conclusions
These
suggest
gene
circulating
white
cells
are
coordinated
differentially
regulation
immune
responses
long-term
progression
mechanisms
which
have
yet
be
elucidated.
Язык: Английский
The Transcription of Transposable Elements Differentially Regulated by SVAs in the Major Histocompatibility Complex Class I Region of a Parkinson’s Progression Markers Initiative Cohort
Journal of Molecular Pathology,
Год журнала:
2025,
Номер
6(1), С. 1 - 1
Опубликована: Янв. 6, 2025
Background/Objectives:
The
highly
polymorphic
Major
Histocompatibility
Complex
(MHC)
genomic
region,
located
on
the
short
arm
of
chromosome
6,
is
implicated
genetically
in
Parkinson’s
disease
(PD),
a
progressive
neurodegenerative
disorder
with
motor
and
non-motor
symptoms.
Previously,
we
reported
significant
associations
between
SINE-VNTR-Alu
(SVA)
expression
quantitative
trait
loci
(eQTLs)
Human
Leucocyte
Antigen
(HLA)
class
I
genotypes
PD.
In
this
study,
aimed
to
evaluate
SVA
their
regulatory
effects
transposable
element
(TE)
transcription
MHC
region.
Methods:
Transcriptome
data
from
peripheral
blood
cells
1530
individuals
Progression
Markers
Initiative
(PPMI)
cohort
were
reanalyzed
for
TE
gene
using
publicly
available
bioinformatics
tools,
including
Salmon
Matrix-eQTL.
Results:
Four
structurally
SVAs
regulated
18
distinct
clusters
235
loci,
comprising
LINEs
(33%),
SINEs
(19%),
LTRs
(35%),
ancient
transposon
DNA
elements
(12%)
near
HLA
genes.
transcribed
TEs
predominantly
short,
an
average
length
445
nucleotides.
these
varied
significantly
terms
types,
numbers,
transcriptional
activation
or
repression.
SVA-regulated
RNAs
appear
function
as
enhancer-like
elements,
differentially
influencing
genes,
non-HLA
noncoding
RNAs.
Conclusions:
These
findings
highlight
roles
associated
complex
networks
governing
coding
potential
implications
immune
susceptibility.
Язык: Английский
scTCR-seq and HTS reveal a special novel TRBD2-TRBJ1 rearrangement in mammalian TRB CDR3 repertoire
BMC Genomics,
Год журнала:
2025,
Номер
26(1)
Опубликована: Апрель 4, 2025
Mammalian
T
cell
receptor
(TCR)
beta-chain
(TRB)
V-D-J
rearrangement
mainly
follows
the
"12/23
rule",
and
"D-J
preceding
V-(D-J)
rearrangement".
Owing
to
physical
position
of
D-J-C
cluster
in
TRB
locus,
TRBD2
(D2)
gene
cannot
directly
perform
inversional
or
deletional/loop-out
with
TRBJ1
(J1)
gene.
Our
previous
studies
revealed
a
single
reverse
TRBV30
(TRBV31
mice)
mammalian
which
can
cause
indirect
D2
J1
gene;
however,
mechanism
proportion
involved
germline
are
unknown.
We
obtained
CDR3
repertoires
thymus
peripheral
tissues
from
humans
mice
by
HTS
scTCR-seq
found
that
14%
rearrangements
is
D2-J1
(D2-J2
account
for
approximately
86%).
The
V30
preferentially
performs
(V30-D2),
leading
V30-D2-J1
humans,
D1
(V30-D1),
allowing
forward
V
genes
(Vx)
Vx-D2-J1
rearrangement.
further
were
present
more
than
24%
15%
rhesus
monkeys
bats,
respectively.
Moreover,
bovine
containing
D1J1C1,
D3J3C3,
D2J2C2
clusters,
11%
D3-J1
22%
D2-J3
found.
This
study
provides
new
perspective
feasible
solution
research
on
significance
special
recombination
pattern
locus
repertoire
formed
Язык: Английский
Analysis of HLA-G 14 bp Insertion/Deletion Polymorphism and HLA-G, ILT2 and ILT4 Expression in Head and Neck Squamous Cell Carcinoma Patients
Diseases,
Год журнала:
2024,
Номер
12(2), С. 34 - 34
Опубликована: Фев. 8, 2024
HLA-G
is
the
checkpoint
molecule
involved
in
suppression
of
immune
response.
Increased
expression
and
its
ILTs
receptors
have
been
correlated
with
tumor
progression
various
cancer
types.
In
head
neck
squamous
cell
carcinoma
(HNSCC)
tumors,
effect
HLA-G,
ILT2
ILT4
on
development
has
to
be
explained.
The
34
HNSCC
patients
98
controls
were
genotyped
for
14
bp
ins/del
polymorphism.
lesions,
mRNA
was
analysed
using
real-time
PCR.
association
between
clinical
variables
(age
at
onset,
TNM
staging
system
p16
positivity)
also
evaluated.
No
genetic
risk
detected
(p
>
0.05).
However,
non-metastatic
group,
a
significantly
higher
noted
tumors
T4
stage
compared
those
T1
T2
stages
=
0.0289).
increased
vs.
metastatic
0.0269).
Furthermore,
T1+T2
T3
0.0495).
Our
results
suggest
that
creates
an
immunological
microenvironment
development.
Язык: Английский
Exploring SVA Insertion Polymorphisms in Shaping Differential Gene Expressions in the Central Nervous System
Biomolecules,
Год журнала:
2024,
Номер
14(3), С. 358 - 358
Опубликована: Март 17, 2024
Transposable
elements
(TEs)
are
repetitive
which
make
up
around
45%
of
the
human
genome.
A
class
TEs,
known
as
SINE-VNTR-Alu
(SVA),
demonstrate
capacity
to
mobilise
throughout
genome,
resulting
in
SVA
polymorphisms
for
their
presence
or
absence
within
population.
Although
studies
have
previously
highlighted
involvement
TEs
neurodegenerative
diseases,
such
Parkinson’s
disease
and
amyotrophic
lateral
sclerosis
(ALS),
exact
mechanism
has
yet
be
identified.
In
this
study,
we
used
whole-genome
sequencing
RNA
data
ALS
patients
healthy
controls
from
New
York
Genome
Centre
Consortium
elucidate
influence
reference
on
gene
expressions
genome-wide
central
nervous
system
(CNS)
tissues.
To
investigate
this,
applied
a
matrix
expression
quantitative
trait
loci
analysis
that
insertion
can
significantly
modulate
numerous
genes,
preferentially
trans
position
tissue-specific
manner.
We
also
highlight
SVAs
regulate
mitochondrial
genes
well
HLA
MAPT
loci,
associated
diseases.
conclusion,
study
continues
bring
light
effects
polymorphic
regulation
further
highlights
importance
pathology.
Язык: Английский
SVA Regulation of Transposable Element Clustered Transcription within the Major Histocompatibility Complex Genomic Class II Region of the Parkinson’s Progression Markers Initiative
Genes,
Год журнала:
2024,
Номер
15(9), С. 1185 - 1185
Опубликована: Сен. 9, 2024
SINE-VNTR-Alu
(SVA)
retrotransposons
can
regulate
expression
quantitative
trait
loci
(eQTL)
of
coding
and
noncoding
genes
including
transposable
elements
(TEs)
distributed
throughout
the
human
genome.
Previously,
we
reported
that
expressed
SVAs
leucocyte
antigen
(HLA)
class
II
genotypes
on
chromosome
6
were
associated
significantly
with
Parkinson’s
disease
(PD).
Here,
our
aim
was
to
follow-up
previous
study
evaluate
SVA
associations
their
regulatory
effects
transcription
TEs
within
HLA
genomic
region.
We
reanalyzed
transcriptome
data
peripheral
blood
cells
from
Progression
Markers
Initiative
(PPMI)
for
1530
subjects
TE
gene
RNAs
publicly
available
computing
packages.
Four
structurally
polymorphic
20
distinct
clusters
235
represented
by
LINES
(37%),
SINES
(28%),
LTR/ERVs
(23%),
ancient
transposon
DNA
(12%)
are
located
in
close
proximity
genes.
The
transcribed
mostly
short
length,
an
average
size
389
nucleotides.
numbers,
types
profiles
positive
negative
regulation
varied
markedly
between
four
SVAs.
appear
be
enhancer-like
coordinated
differentially
Future
work
mechanisms
underlying
potential
impact
is
essential
elucidating
roles
normal
cellular
processes
pathogenesis.
Язык: Английский
Exploring the HLA complex in autoimmunity: From the risk haplotypes to the modulation of expression
Clinical Immunology,
Год журнала:
2024,
Номер
265, С. 110266 - 110266
Опубликована: Июнь 7, 2024
The
genes
mapping
at
the
HLA
region
show
high
density,
strong
linkage
disequilibrium
and
polymorphism,
which
affect
association
of
class
I
II
with
autoimmunity.
We
focused
on
haplotypes,
genomic
structures
consisting
an
array
specific
alleles
showing
some
degrees
genetic
different
autoimmune
disorders.
GWASs
in
many
pathologies
have
identified
variants
either
coding
loci
or
flanking
regulatory
regions,
both
that
are
frequently
associated
increased
risk
may
influence
gene
expression.
discuss
relevance
expression
because
level
surface
heterodimers
determines
number
complexes
presenting
self-antigen
and,
thus,
strength
pathogenic
autoreactive
T
cells
immune
response.
Язык: Английский
Human Leukocyte Antigen and microRNAs as Key Orchestrators of Mild Cognitive Impairment and Alzheimer’s Disease: A Systematic Review
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(15), С. 8544 - 8544
Опубликована: Авг. 5, 2024
The
expression
of
inflamma-miRs
and
human
leukocyte
antigen
(HLA)
haplotypes
could
indicate
mild
cognitive
impairment
(MCI)
Alzheimer’s
disease
(AD).
We
used
international
databases
to
conduct
a
systematic
review
studies
on
HLA
variants
meta-analysis
research
microRNAs
(miRNAs).
aimed
analyze
the
discriminative
value
miRNAs
in
MCI,
AD
controls
evaluate
protective
or
causative
effect
decline,
establish
role
as
biomarkers
for
early
detection
AD,
find
possible
link
between
HLA.
Statistical
analysis
was
conducted
using
Comprehensive
Meta-analysis
software,
version
2.2.050
(Biostat
Inc.,
Englewood,
NJ,
USA).
sizes
were
estimated
by
logarithm
base
2
fold
change.
revealed
that
some
variants,
such
HLA-B*4402,
HLA-A*33:01,
HLA-DPB1,
HLA-DR15,
HLA-DQB1*03:03,
HLA-DQB1*06:01,
HLA-DQB1*03:01,
SNPs
HLA-DRB1/DQB1,
HLA-DQA1,
predisposed
decline
before
occurrence
while
HLA-A1*01,
HLA-DRB1∗13:02,
HLA-DRB1*04:04,
HLA-DRB1*04:01
demonstrated
role.
identified
let-7
miR-15/16
AD.
association
these
two
miRNA
families
predispose
be
screening
prevention
MCI.
Язык: Английский
Exploring SVA Insertion Polymorphisms in Shaping Differential Gene Expression in the Central Nervous System
Опубликована: Дек. 26, 2023
Transposable
elements
(TEs)
are
repetitive
which
make
up
around
45%
of
the
human
genome.
A
class
TEs
known
as
SINE-VNTR-Alu
(SVA)
demonstrate
capacity
to
mobilise
throughout
genome,
resulting
in
SVA
polymorphisms
for
presence
or
absence
within
population.
Although
studies
have
previously
highlighted
involvement
neurodegenerative
diseases,
such
Parkinson’s
disease
and
amyotrophic
lateral
sclerosis
(ALS),
however
exact
mechanism
has
yet
be
identified.
In
this
study
we
used
whole
genome
sequencing
RNA
data
ALS
patients
healthy
controls
from
New
York
Genome
Center
Consortium,
elucidate
influence
reference
on
gene
expression
genome-wide
central
nervous
system
(CNS)
tissues.
To
investigate
this,
applied
matrix
quantitative
trait
loci
analysis
demonstrated
that
insertion
can
significantly
modulate
numerous
genes,
preferentially
trans
position,
a
tissue-specific
manner.
We
also
highlight
SVAs
regulate
mitochondrial
genes
well
HLA
MAPT
loci,
associated
disease.
conclusion,
continues
bring
light
effects
polymorphic
regulation
further
highlights
importance
pathology.
Язык: Английский