Genetic architecture of human brain evolution
Current Opinion in Neurobiology,
Год журнала:
2023,
Номер
80, С. 102710 - 102710
Опубликована: Март 30, 2023
Comparative
studies
of
hominids
have
long
sought
to
identify
mutational
events
that
shaped
the
evolution
human
nervous
system.
However,
functional
genetic
differences
are
outnumbered
by
millions
nearly
neutral
mutations,
and
developmental
mechanisms
underlying
system
specializations
difficult
model
incompletely
understood.
Candidate-gene
attempted
map
select
human-specific
neurodevelopmental
functions,
but
it
remains
unclear
how
contextualize
relative
effects
genes
investigated
independently.
Considering
these
limitations,
we
discuss
scalable
approaches
for
probing
contributions
differences.
We
propose
a
systems-level
view
will
enable
more
quantitative
integrative
understanding
genetic,
molecular
cellular
underpinnings
evolution.
Язык: Английский
Massively parallel assessment of gene regulatory activity at human cortical structure associated variants
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 8, 2025
Abstract
Genetic
association
studies
have
identified
hundreds
of
largely
non-coding
loci
associated
with
inter-individual
differences
in
the
structure
human
cortex,
though
specific
genetic
variants
that
impact
regulatory
activity
are
unknown.
We
implemented
a
Massively
Parallel
Reporter
Assay
(MPRA)
to
measure
9,092
cortical
DNA
neural
progenitor
cells
during
Wnt
stimulation
and
at
baseline.
918
potential
from
150
(76%
studied),
which
>50%
showed
allelic
effects.
modified
subset
functioned
as
condition-dependent
enhancers.
Regulatory
MPRA
was
induced
by
Alu
elements
were
hypothesized
contribute
expansion.
The
regionally
disrupt
motifs
is
likely
mediated
through
levels
transcription
factor
expression
development,
further
clarifying
molecular
mechanisms
altering
structure.
Язык: Английский
Comparative genomics illuminates karyotype and sex chromosome evolution of sharks
Cell Genomics,
Год журнала:
2024,
Номер
4(8), С. 100607 - 100607
Опубликована: Июль 11, 2024
Chondrichthyes
is
an
important
lineage
to
reconstruct
the
evolutionary
history
of
vertebrates.
Here,
we
analyzed
genome
synteny
for
six
chondrichthyan
chromosome-level
genomes.
Our
comparative
analysis
reveals
a
slow
rate
chromosomal
changes,
with
infrequent
but
independent
fusions
observed
in
sharks,
skates,
and
chimaeras.
The
common
ancestor
had
proto-vertebrate-like
karyotype,
including
presence
18
microchromosome
pairs.
X
chromosome
conversed
shared
by
all
suggesting
likely
origin
sex
at
least
181
million
years
ago.
We
characterized
Y
chromosomes
two
sharks
that
are
highly
differentiated
from
except
small
young
stratum
pseudoautosomal
region.
found
shark
lack
global
dosage
compensation
dosage-sensitive
genes
locally
compensated.
study
on
evolution
enhances
our
understanding
vertebrate
evolution.
Язык: Английский
Transcription of Endogenous Retroviruses: Broad and Precise Mechanisms of Control
Viruses,
Год журнала:
2024,
Номер
16(8), С. 1312 - 1312
Опубликована: Авг. 17, 2024
Endogenous
retroviruses
(ERVs)
are
the
remnants
of
retroviral
germline
infections
and
highly
abundant
in
genomes
vertebrates.
At
one
time
considered
to
be
nothing
more
than
inert
‘junk’
within
genomes,
ERVs
have
been
tolerated
host
over
vast
timescales,
their
study
continues
reveal
complex
co-evolutionary
histories
respective
species.
For
example,
multiple
instances
characterized
having
‘borrowed’
for
normal
physiology,
from
single
copies
ones
involved
various
regulatory
networks
such
as
innate
immunity
during
early
development.
Within
cell,
accessibility
is
normally
tightly
controlled
by
epigenetic
mechanisms
DNA
methylation
or
histone
modifications.
However,
these
silencing
reversible,
alterations
chromatin
landscape
can
thus
lead
aberrant
expression,
observed
abnormal
cellular
environments
tumors.
In
this
review,
we
focus
on
ERV
transcriptional
control
draw
parallels
distinctions
concerning
loss
regulation
disease,
well
precise
Язык: Английский
Novelty versus innovation of gene regulatory elements in human evolution and disease
Current Opinion in Genetics & Development,
Год журнала:
2024,
Номер
90, С. 102279 - 102279
Опубликована: Ноя. 26, 2024
Язык: Английский
Transforming our understanding of species-specific gene regulation
Cell Genomics,
Год журнала:
2024,
Номер
4(4), С. 100540 - 100540
Опубликована: Апрель 1, 2024
Mechanisms
underlying
phenotypic
divergence
across
species
remain
unresolved.
In
this
issue
of
Cell
Genomics,
Hansen,
Fong,
et
al.
Язык: Английский
Uncovering methylation-dependent genetic effects on regulatory element function in diverse genomes
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 24, 2024
ABSTRACT
A
major
goal
in
evolutionary
biology
and
biomedicine
is
to
understand
the
complex
interactions
between
genetic
variants,
epigenome,
gene
expression.
However,
causal
relationships
these
factors
remain
poorly
understood.
mSTARR-seq,
a
methylation-sensitive
massively
parallel
reporter
assay,
capable
of
identifying
methylation-dependent
regulatory
activity
at
many
thousands
genomic
regions
simultaneously,
allows
for
testing
DNA
methylation
expression
on
region-by-region
basis.
Here,
we
developed
multiplexed
mSTARR-seq
protocol
assay
naturally
occurring
human
variation
from
25
individuals
sampled
10
localities
Europe
Africa.
We
identified
6,957
elements
either
unmethylated
or
methylated
state,
this
set
was
enriched
enhancer
promoter
annotations,
as
expected.
The
58%
modulated
by
methylation,
which
generally
associated
with
decreased
RNA
Within
our
elements,
used
allele-specific
analyses
identify
8,020
sites
effects
regulation;
further,
found
that
42.3%
varied
states.
Sites
exhibiting
were
GWAS
EWAS
implicating
them
disease.
Compared
datasets
single
European
individual,
uncovers
dramatically
more
effects,
highlighting
importance
including
diverse
assays
aim
processes.
Язык: Английский
Comprehensive mapping of genetic variation at Epromoters reveals pleiotropic association with multiple disease traits
Nucleic Acids Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 19, 2024
Abstract
There
is
growing
evidence
that
a
wide
range
of
human
diseases
and
physiological
traits
are
influenced
by
genetic
variation
cis-regulatory
elements.
We
others
have
shown
subset
promoter
elements,
termed
Epromoters,
also
function
as
enhancer
regulators
distal
genes.
This
opens
paradigm
in
the
study
regulatory
variants,
single
nucleotide
polymorphisms
(SNPs)
within
Epromoters
might
influence
expression
several
(distal)
genes
at
same
time,
which
could
disentangle
identification
disease-associated
Here,
we
built
comprehensive
resource
using
newly
generated
publicly
available
high-throughput
reporter
assays.
showed
display
intrinsic
epigenetic
features
distinguish
them
from
typical
promoters.
By
integrating
Genome-Wide
Association
Studies
(GWAS),
Quantitative
Trait
Loci
(eQTLs)
3D
chromatin
interactions,
found
variants
concurrently
associated
with
more
disease
traits,
compared
To
dissect
impact
Epromoter
evaluated
their
on
activity
analyzing
allelic-specific
assays
provided
reliable
examples
pleiotropic
Epromoters.
In
summary,
our
represents
supporting
role
Язык: Английский