Genome biology,
Journal Year:
2017,
Volume and Issue:
18(1)
Published: Feb. 20, 2017
Structural
variation
(SV)
influences
genome
organization
and
contributes
to
human
disease.
However,
the
complete
mutational
spectrum
of
SV
has
not
been
routinely
captured
in
disease
association
studies.
We
sequenced
689
participants
with
autism
disorder
(ASD)
other
developmental
abnormalities
construct
a
genome-wide
map
large
SV.
Using
long-insert
jumping
libraries
at
105X
mean
physical
coverage
linked-read
whole-genome
sequencing
from
10X
Genomics,
we
document
seven
major
classes
~5
kb
resolution.
Our
results
encompass
11,735
distinct
sites,
38.1%
which
are
novel
16.8%
balanced
or
complex.
characterize
16
recurrent
subclasses
complex
(cxSV),
revealing
that:
(1)
cxSV
larger
rarer
than
canonical
SV;
(2)
each
harbors
14
on
average;
(3)
84.4%
cxSVs
involve
inversion;
(4)
most
(93.8%)
have
delineated
previous
Rare
SVs
more
likely
disrupt
coding
regulatory
non-coding
loci,
particularly
when
truncating
constrained
disease-associated
genes.
also
identify
multiple
cases
catastrophic
chromosomal
rearrangements
known
as
chromoanagenesis,
including
somatic
chromoanasynthesis,
extreme
germline
chromothripsis
events
involving
up
65
breakpoints
60.6
Mb
across
four
chromosomes,
further
defining
rare
categories
cxSV.
These
data
provide
foundational
morbid
demonstrate
previously
underappreciated
abundance
diversity
that
should
be
considered
genomic
studies
Nature Communications,
Journal Year:
2020,
Volume and Issue:
11(1)
Published: Nov. 20, 2020
Abstract
Identifying
pathogenic
variants
and
underlying
functional
alterations
is
challenging.
To
this
end,
we
introduce
MutPred2,
a
tool
that
improves
the
prioritization
of
amino
acid
substitutions
over
existing
methods,
generates
molecular
mechanisms
potentially
causative
disease,
returns
interpretable
pathogenicity
score
distributions
on
individual
genomes.
Whilst
its
performance
state-of-the-art,
distinguishing
feature
MutPred2
probabilistic
modeling
variant
impact
specific
aspects
protein
structure
function
can
serve
to
guide
experimental
studies
phenotype-altering
variants.
We
demonstrate
utility
in
identification
structural
mutational
signatures
relevant
Mendelian
disorders
de
novo
mutations
associated
with
complex
neurodevelopmental
disorders.
then
experimentally
validate
several
identified
patients
such
argue
mechanism-driven
human
inherited
disease
have
potential
significantly
accelerate
discovery
clinically
actionable
Frontiers in Cellular Neuroscience,
Journal Year:
2019,
Volume and Issue:
13
Published: Aug. 20, 2019
Autism
Spectrum
Disorder
(ASD)
is
one
of
the
most
prevalent
neurodevelopmental
disorders,
affecting
an
estimated
1
in
59
children.
ASD
highly
genetically
heterogeneous
and
may
be
caused
by
both
inheritable
de
novo
gene
variations.
In
past
decade,
hundreds
genes
have
been
identified
that
contribute
to
serious
deficits
communication,
social
cognition,
behavior
patients
often
experience.
However,
these
only
account
for
10-20%
cases,
with
similar
pathogenic
variants
diagnosed
on
very
different
levels
spectrum.
this
review,
we
will
describe
genetic
landscape
discuss
how
modifiers
such
as
copy
number
variation,
single
nucleotide
polymorphisms,
epigenetic
alterations
likely
play
a
key
role
modulating
phenotypic
spectrum
patients.
We
also
consider
can
alter
convergent
signaling
pathways
lead
impaired
neural
circuitry
formation.
Lastly,
review
sex-linked
clinical
implications.
Further
understanding
mechanisms
crucial
comprehending
developing
novel
therapies.
Science,
Journal Year:
2016,
Volume and Issue:
352(6281)
Published: March 31, 2016
Improving
on
the
gorilla
genome
Access
to
complete,
high-quality
genomes
of
nonhuman
primates
will
also
help
us
understand
human
biology.
Gordon
et
al.
used
long-read
sequencing
technology
improve
data
our
close
relative
gorilla.
Sequencing
from
a
single
individual
decreased
assembly
fragmentation
and
recovered
previously
missed
genes
noncoding
loci.
Mapping
short-read
sequences
additional
gorillas
helped
reconstruct
“pan”
sequence
documenting
genetic
variation.
Comparison
with
revealed
species-specific
differences
ranging
in
size
one
thousands
bases
length,
including
some
that
are
likely
affect
gene
regulation.
Science
,
this
issue
p.
10.1126/science.aae0344
