Trends in Genetics,
Journal Year:
2020,
Volume and Issue:
37(8), P. 717 - 729
Published: Nov. 13, 2020
Mutation
of
the
human
genome
results
in
three
classes
genomic
variation:
single
nucleotide
variants;
short
insertions
or
deletions;
and
large
structural
variants
(SVs).
Some
mutations
occur
during
normal
processes,
such
as
meiotic
recombination
B
cell
development,
others
result
from
DNA
replication
aberrant
repair
breaks
sequence-specific
contexts.
Regardless
mechanism,
are
subject
to
selection,
some
hotspots
can
manifest
disease.
Here,
we
discuss
regions
prone
mutation,
mechanisms
contributing
mutation
susceptibility,
processes
leading
their
accumulation
somatic
genomes.
With
further,
more
accurate
sequencing,
additional
hotspots,
mechanistic
details
formation,
relevance
evolution
disease
likely
be
discovered.
Cell,
Journal Year:
2022,
Volume and Issue:
185(14), P. 2559 - 2575.e28
Published: June 9, 2022
A
central
goal
of
genetics
is
to
define
the
relationships
between
genotypes
and
phenotypes.
High-content
phenotypic
screens
such
as
Perturb-seq
(CRISPR-based
with
single-cell
RNA-sequencing
readouts)
enable
massively
parallel
functional
genomic
mapping
but,
date,
have
been
used
at
limited
scales.
Here,
we
perform
genome-scale
targeting
all
expressed
genes
CRISPR
interference
(CRISPRi)
across
>2.5
million
human
cells.
We
use
transcriptional
phenotypes
predict
function
poorly
characterized
genes,
uncovering
new
regulators
ribosome
biogenesis
(including
CCDC86,
ZNF236,
SPATA5L1),
transcription
(C7orf26),
mitochondrial
respiration
(TMEM242).
In
addition
assigning
gene
function,
allow
for
in-depth
dissection
complex
cellular
phenomena—from
RNA
processing
differentiation.
leverage
this
ability
systematically
identify
genetic
drivers
consequences
aneuploidy
discover
an
unanticipated
layer
stress-specific
regulation
genome.
Our
information-rich
genotype-phenotype
map
reveals
a
multidimensional
portrait
function.
