Dutch language

How to pronounce aberrant in Dutch?

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it's my first talk in a plenary session
so I will try to do my best not keeping
you for too long knowing that you all
want to enjoy the lunch and the talk
that I am waiting for you after my talk
actually this is my emotional shot over
the last few months so this is me when I
received the acceptation
email from abstract I was like yes this
is good news I can present the results I
worked so hard for this is great but
then I realized what kind of session it
really was not the type of presentation
that I've used to do but a sort of
scientific one-woman show without desk
or slides so I had to think a lot think
about how to present my work making it
easy to understand without being boring
and how not to be too stressed and
finally this is me right now talking in
front of you with all my mixed feelings
so what I'm going to talk about for the
next 10 minutes is haemophilia a and
especially genetics of haemophilia a and
the importance of using the highly
effective molecular tools that have been
developed since a couple of years to
help us understand more about the
causality of variants in regions of the
genes that were not stood it before like
the introns I realize when people ask me
on what I'm working on that it's not
easy to explain my fascination for
hemophilia but I am convinced that we
all have to keep trying to explain the
mechanism of this terrible disease as we
know haemophilia a is constitutional
bleeding disease caused by coagulation
protein defects the factor 8 it can be a
synthesis defect or functional defect
due to the presence of pathogenic
variants in the FH gene which spans 26
exams and 186 kilobase and it's
important to
identify the molecular defect
responsible for the disease because it
helps for the diagnosis optimization and
the characterization of careers but the
issue we have is that despite an
exhaustive screening of the full coding
region of the gene we still have 5% of
hemophilia a patient that don't have any
identified variant so I just want to
remind you this because it will help us
a understanding later very briefly and
easy a gene is composed of exons and
introns and after the transcription
there is a splicing step where the
introns are eliminated and only the
exams remain in the mRNA before the
protein translation so until recently we
all thought that introns were kind of
useless because they are not stood it
because they are eliminated before the
recession so they were not - did in the
research of disease-causing variants but
in the last few years some teams I've
begun to study with introns and they
discovered that variants deeply located
in vision trans male finally girls
haemophilia a by altering all these
splicing process and this work can be
done through next-generation sequencing
that has provided significant
improvements for complete of aging
analysis so as a work I'm going to
present was mostly realized during the
year I spent in Canada in the team of
David Lilly crap even if my team members
try to distract me a lot with some
hockey games and protein testing I have
to admit that I was way more excited by
how to characterize intronic variants in
our patient from France and from Canada
with no identified variants using NGS
will gene sequencing method so how did
we do that first
next generation sequencing we wanted to
amplify the total f-18 directly with
long runs PCR and directly sequence
their product but after three or four
months of optimization it was how to
these products were how to amplify and
we were afraid of not have enough DNA
material and not enough time for this so
we decided to give at this method start
all over so it was very disappointing
for me but it's also as works research
and choose another NGS method so we use
a capture method for that the first step
is to create a probe design and each
probe will improvise on a small part of
the gene and Saru covering the wall gene
exams in introns we developed a small
panel with both wall f/8 and ribbon
factor genes which represent Iran 400 kV
with Judy 20 patients 14 from France 6
from Canada having severe moderate and
mild haemophilia a with no variant in
their FH sequence and after the
sequencing and the bioinformatic
analysis we obtained 1000 variants for
each patient that we had to filter with
different criterias we also use the
aramid software that can predict the
changes and display side that the
variant can cause so this is for the
sequencing part but NGS is not
sufficient when you find convenient
variant you have to prove the pathogenic
effect with functional experiments like
the mRNA analysis for that you need a
Rene sample from you patient from a
simple blood extraction you reverse
transcript this RNA into DNA
and you sequence the cDNA cDNA is
supposed to be the succession of exons
that I told you before and what you hope
to find is an aberrant insertion of an
in training sequence
so absolutely not supposed to be here
between two exams of this DNA and this
insertion should be caused by the
intronic variant you found this
technique is very difficult to because
other one transcript are very sneaky
they're very unstable so the hive a lot
you can very easily miss them and you
have to do the experiments several times
to be sure of your results so now that
we have the techniques let's get with
the results starting with the NGS
results after all the filtering and
analyzing process we finally get sixteen
dip into anak variance when you find
potentially interesting variants you can
classify them from likely benign to like
the pathogenic depending on the in
silico prediction and the complimentary
analysis in canada when i was trying to
survive with the minus 30 degrees
outside because this is survival I can
let you imagine my excitation I could
even say my relief when we found that
for of this variant will likely
pathogenic after doing our functional
assays the first two variants you see
correspond to two patients and they had
in the cDNA sequence that kind of
aberrant intronic insertion I told you
before so a sequence that is not
supposed to be here between two exons of
the cDNA caused by a strong modification
of the splice site by the deep intranet
variant which is located at the exact
same localization welcome from the
sequence inserted and during the
translation the insertion of this
sequence is causing a frameshift and the
operation of the stop codon consequently
are truncated non-functional protein may
seem unbelievable that a variant located
8500 days five
the exam may affect the protein but I
can assure you it's true
this animal it doesn't concern all the
transcript the patient is still
sensitizing normal f/8 with normal
transcript that's why he has a moderate
or my phenotype and not severe the third
variant you see leads to maximum
skipping and the last variant was
already described in the literature we
also found five variants of uncertain
significance why do we say uncertain
because it may be that the modification
of the splice site is not that strong
and simply our functional assay are
still in progress so we don't have
confirm results yet it may also be
variants that are apparently not
pathogenic themselves but we saw that
they are often associated with the
disease and with more pathogenic
variants responsible for the disease we
also found seven variants that were
finally likely benign so with a few or
no change in the splice site and no
functional effects finally and
unfortunately we still have five
patients with no identified Lorient in
their sequence one last result that I
want to tell you was totally unexpected
and it shows the importance of
sequencing f/8 and Vanderbilt factor
genes at the same time this result
consumed a patient that were diagnosed
years ago as a moderate haemophilia a
patient with no identified variants in
is FH sequence and we saw after we found
after the sequencing to exonic variants
in his vwf sequence volumes described as
causing von Webern disease so we are
totally confused and after verification
we realize that this patient was
completely misdiagnosed he is not a
hemophiliac patient at all but he has
been villain
so thanks to this two-day bill patient
will now have a better care so what I
really wants you to remember from my
talk is that this result strongly
corroborate that
hemophilia a can because they deep in
tronic variance so variance in regions
of the gene that were absolutely never
studied until very recently in France
will present 95% of the f18 so it's far
more work than just reading the exams
finally these results I asked us to lead
us to ask ourselves when does a negative
result is really negative did we use a
good technique did we interpret a tip
the data correctly and can we still go
far beyond the gene to find what caused
the disease that playground seems
infinite thank you for your attention
[Applause]

it's my first talk in a plenary session

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aberrant::adjective | Spocien Dictionary

aberrant

adjective

/ə'bɛrənt/

markedly different from an accepted norm

Type	Words
Synonyms	deviant, deviate
Derivation	aberrance, aberrancy

aberrant behavior.

aberrant::noun | Spocien Dictionary

aberrant

noun

/ə'bɛrənt/

one whose behavior departs substantially from the norm of a group

Type	Words
Type of	anomaly, unusual person
Derivation	aberrate

How to pronounce aberrant in Dutch?

aberrant::adjective | Spocien Dictionary

abandonment

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aberrant::noun | Spocien Dictionary

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