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everybody, to Wednesday Nite >> Tom Zinnen: Welcome,
I'm Tom Zinnen. I work here at the University
of Wisconsin-Madison
I also work for UW Extension Biotechnology Center.
And on behalf of our partners at Cooperative Extension.
and Wisconsin Public Television, the Wisconsin Alumni Association
at the Lab. We do this every Wednesday
night, 50 times a year. Tonight I'm delighted to be able
to welcome Jennifer Laffin to Wednesday Nite at the Lab.
She'll be talking about her work
Laboratory of Hygiene and telltale clues using genetic
tests to diagnose diseases in children.
Jennifer is from Kaukauna,
here in genetics in 1996. WShe went over to Iowa City ande
got her PhD in genetics in 2003 and came back to Madison
with a fellowship in 2006 and then as an assistant professor
in 2008, and just this year she became co-director of the
clinic. I look forward to her talk.
Please join me in welcoming Jennifer Laffin
to Wednesday Nite at the Lab. [APPLAUSE]
Jennifer Laffin: Thank you. Thank you, everyone.
It's a pleasure to be here. So I'm Jennifer Laffin.
I'm co-director of the Clinical Genetics Laboratories at the
State Lab of Hygiene. The State Lab of Hygiene houses
the Clinical Genetics Laboratories at the UW.
So we have sections in
and biochemical genetics. So that covers all the areas ofs
clinical genetic laboratory testing.
So it's a really great place
And in the audience is my co-director, Dr. Raca.
We oversee the cytogenetic
genetic section. section and the molecular
talk a little bit about the types of testing that we do, and
then give you some examples of
through our door. So you can kind of get a feel of
what happens to a specimen, how do we use our different
techniques and how do we use our
answers for our patients. And then learn something as well
about the biology and kind of feed the research and feed the
clinical side as well.
together to try to bring better So all tpatient care. of work
So the types of testing, the
on, so we do everything from types of specimens that we work
amniotic fluid specimens, prchorionic villi specimens,ke
so little placental biopsies, to oncology testing.
So we do a lot of testing of
lymphomas and tumors to try to patients that have leukemias,
can be both prognostic and drive identify genetic markers that
And we also do a lot of testing for individuals who have
developmental issues. We do testing for fertility,
anything that has an genetic
And genetic aspects, as you're aspect.
hitting all fields of medicine. So genetics is really growing
and growing fast. So tonight I'll be talking about
cytogenetics and molecular
opportunity here to use our research tools as well as our
clinical tools to help our
So I'll start with a little primer in cytogenetics.
So cytogenetics 101.
work at all levels or all So resolutions of genetics.to
So we start with chromosomes
protein and they carry our which are composed of our DNA
And then go all the way down to gmolecular so we can look ats.
bases as well.
structure and function of So cytogechromosomes-- study of
Yeah? >> Could you tap your
microphone? Thank you.
That activates it.
Okay, so in order to see >> Okay, sorry.
tissue that's actively dividing. chromosomes we need living
specimens that we have, we get So if you remember the types of
that cells wouldn't be actively bdividing in your peripheralpe
blood and we also get tumor specimens as well which are
actively dividing, amniotic fluid specimens actively
dividing. So we need living tissues in
order for it to go. So we have cells that we either
induce to go into mitosis or
cells that are already actively into cell ddividing.r we look at
So here we have a couple
what happens. dAnd here's, on the right hande,
side, we have a diagram of
at the DNA inside of those really what's happening looking
So at interphase we have DNA cells.
you can get activation of genes and silencing of genes, and then
as cells go through mitosis, we need those chromosomes to
condense and then normally what would happen is the chromosomes
that condense line up at the
split into the two daughter metaphase pcells.nd then be
So what we do is we need to capture those chromosomes at
their most condensed state. So we poison those microtubules
that would normally connect and then pull the chromosomes to
their daughter cells. So we depolymerize those
microtubules and then hold those
So after we've done that, we cells in metaphase.
So we use a hypotonic treatment that swells the cells and helps
with chromosome spreading.
need to put those chromosomes on So what needs to happen is we
actually visualize them. a microscope slide so we can
we fix them so they stay put. So that also lyses any red blood
cells that might be still floating around but it stops
that hypotonic swelling.
cytogenetics. So it's the slide making and the
staining portion. So when we drop the chromosomes
there, we have to make sure that
so you don't end up with everything happens just so
So when you drop the cell suspension on a microscope
slide, that the chromosomes don't get spread off into every
which way.
little puddle so that we can We need them to stay in a nice
nucleus, one nucleus. So we can count the chromosomes
and look at their banding.
that they're all crumpled up and But we don't want them so tight
you can't really identify which layingchromosome is which.r that
So we drop the suspension of
microscope slide. They need to dry at exactly the
right temperature and the right humidity so that you don't get
overspreading, underspreading,
and band nice. and that everything will stain
then they're treated with The slides trypsin. baked and
So these are pictures from our
So actually the image over here lis one of our drying chambers.
So a technologist will be there with a patient's specimen, drop
the slide, put the slide in the drying chamber, this has exactly
the right humidity and
chromosomes dry nicely, and then temperature so that the
concentration at the microscope weright next door here.and
But then after they're baked, then they go through a process
of trypsin, so that eats the
stain. proteins a little bit, and then
And then they get cover-slipped Soand then sent out to our.
technologists for analysis. So what happens most often, now
we have a slide scanner, an automated slide scanner that
will go through and try to look for metaphases for us, but we do
often for like prenatal specimens sit at the scope and
look through the whole entire slide looking for the best
metaphase spread. So this image right up here is
what you would see under the
So the cell is spread and each microscope.
chromosomes. of these are individual
46 chromosomes, and then a So there should be
find one, one, make sure you technologist will go through and
band for band and make sure that have both chromosome ones and go
orientation and that they're all the bands are in the right
So there aren't deletions or actually present.
that. So then we also the capabilities
of or we have software that allows us to electronically cut
out the chromosomes and then
So right here you can see all arrangthe chromosomes.ogram.
We have chromosome 1 through 22 are autosomes.
And then males have an X and a Y
So with every case that we have we got through and we make sure
that everything is as it should be or if there's a particular
abnormality that we're
So the next step up in expecting, that that's there.
fluorescence in situ resolution that we have, we have
molecular genetic techniques. hySo fluorescence in siture
hybridization, or FISH, allows
part of the genome. So what we can do is we can take
the piece of the genome that
label it with a fluorescent probe and then stick it to the
genome. So you make that little
fluorescent probe and then you
hybridize it either to can hybridize it, you can
dots or you can hybridize it to a metaphase spread and actually
see which chromosome that it's
And there are a lot of different hybridizing to.
answer very specific questions. pSo we have whole chromosometo
paints. Those don't get used as often
anymore now that we have a ray
hybridization. comparative genomic
piece of a chromosome that you But if there's a particular
particular chromosome, like for rexample this image up here, it
was suspected that we know that the banding was consistent with
chromosome 13, is that extra
chromosome 13, is that from the material Y chromosome?ed to that
So you can paint that and see that yes, in fact, there is
chromosome 13 right here and
here came from chromosome Y. that this red material right
probes. So we can look and count to see
how many of each chromosome there are.
We use those often in amniotic
So looking for the common flutrisomies.ns.
So 13, 18, 21 and we can look for the sex chromosomes very
quickly without looking for rearrangements, just know that
there are two 21s, two 13s, two 18s, and so on and so forth.
And then locus specific indicators in the cocktails of
multiple probes can be
that we can look for very manipspecific chromosomalways
rearrangements as well as microdeletion syndromes and
duplications. So this example, these examples
down here, this is from the DiGeorge region.
So this is a recurrent
So we have a piece of DNA that's microdeletion syndrome.
is commonly deleted in the 22Q very specific to the region that
So we can look for that and you can see in this specimen here's
the normal 22.
control probe that kind of marks You have the green is the
chromosome 22. that chromosome as this is
region that is commonly deleted Andin this syndrome.that
So you can see there's a normal 22 and the 22 over here has that
region deleted. We can also, so as far as the
manipulation of these, you can
arrange them so that you can take locus specific probes and
particular breaks in a gene. look for particular fusions or
commonly broken in a particular disease, you can take two probes
and then look for the break apart in the abnormal cells.
The molecular genetics is a lot less visually fancy at the very
beginning.
So we generally start with a The end is still really cool.
patients. We get rid of the red blood
cells and keep the white blood
stored. And then some of our assays do
require RNA but most of our assays require DNA.
And we precipitate out those
precipitate the DNA out of proteins, and then you can
So you can watch that DNA come solution.
So if you think each cell in right out of solution.
DNA, each nucleated cell has your body has about six feet of
really fun to just watch that aball up and then be used for a
really fancy assay like sequencing.
So this is just some examples.
techniques individually because I that will probably take ane
entire night in and of itself,
at things like epigenetic but we can geffect.d we can look
So this gel up here is from our Prader-Willi Angelman assay that
looks for differences in
region on chromosome 15. methylation at a particular
comparative genomic hybridization where we can look
for copy number changes.
deletions and duplications So we can look for very small
We can count the number of within the genome.
using quantitative PCR or copiquantitative RT-PCR.ene
We commonly use southern
We use southern blotting for blotting.
And then of course there's fragile X testing.
for base at a particular region sequencinof interest.look base
And then we do fragment analysis
So first and foremost, our goal is to provide the best patient
care that we can. So the clinical laboratories,
above all, patient care is it what we're about.
So our testing is used for
stratification into the different studies, we have a lot
of studies that the university
clinical testing for those. parAnd then, as part of ourhe
academic mission, we do have
So as we learn things, the research projects on the side.
we get a lot of results, exciting thing about genetics is
scanning techniques where we sometimes, especially the
means. don't know exactly what it
we have an opportunity to really There's something not right and
cases, and really look at is take the next step, in some
does it do and what can we do about it, is this something that
other patients might be interested in as well.
So this brings in new techniques
clinical laboratories. and new testing into the
few, I'll have a few case reports or case examples of the
types of things that we have
So the first case is a come through our lab.
to her family practice clinic five-yearwith leg pain.presented
So in this case there's a lot of
won't get into in depth, but other clinical features that I
many abnormal B cell lymphocyte they did a blasts. they found
So the diagnosis was B cell acute lymphoblastic leukemia.
But now the diagnosis doesn't just end there.
So you take it the next step
They had requested cytogenetics to look for common
rearrangements that happen in leukemias so that you can look
at different treatment options, you can talk about prognosis and
do other stratifications into potential studies and so forth.
So we did her chromosomes and this is what we found.
Can anybody identify what is
Yeah? >> It looks like in one of the
chromosome 14 samples has been a large deletion.
Right.
the chromosome 14. So there's something wrong with
bunch of it that's gone. It looks like there's a whole
How about 10. >> 10, chromosome 10, right.
So there's something very wrong with chromosome 10.
And if you compare the banding
banding of 14, you can see that othose two chromosomes have
switched material.
on 10 and 14. So There are two othertion
abnormalities.
16. You guys are good.
This is good. Right, so 16.
16 has material at the bottom of it.
9.
Great. >> And 9.
So 16 has some material on the You guys are hired.
quite right, but then when you bottom of it that doesn't look
you can see that 9 and 16 have look at the top of chromosome 9
So you have two translocations swapped material.
So then my job is to take it the in this karyotype.
So it's fine to say we have two translocations, but now we need
to know are there any important genes at those break points that
we can tell right now, have any of these translocation occurred
before. Do you have a question?
What causes translocation?
There are probably a lot of things that cause translocation.
So you could have mutation that causes abnormal crossing over.
You can have breaks and rejoining.
It depends, a lot of things depend on where and how you see
it. When you see it in an oncology
specimen, it can sometimes just be sheer chaos.
So there are molecular mutations
swaps. that happen that cause abnormal
that get deregulated. TThere are all kinds of reasons
that translocations happen. But there's not one particular
reason why they happen. So there are some, I'll talk
about one recurrent translocation in humans, but
other than that there's not really a whole lot of recurrent
translocation just in general.
over again in specific types of Scancer, but those mechanisms
aren't really well known. Yeah?
Are they limited to certain chromosome numbers or types?
No, they're not really
numbers or types. liSo there are certain casese
like chronic myeloid leukemia.
translocation. So that has a 9-22
particular disorder. That is the indicator for that
whole host of translocations But in most cases, there are a
disorder and that disorder, tespecially when you starts
talking about oncology. And I didn't bring any really
crazy karyotypes. But there are some, like
myelomas you can have karyotypes
all kinds of translocations. that have 100 chromosomes and
have chromosomes you can't Especially solid tumors, you can
You know it's chromosomal material but you can't really
figure out where the material came from.
So in some cases it's kind of predictable, but predictable we
don't exactly know why. But it keeps it exciting and it
helps us identify, so with all
translocations that helps us these different types of
to see, okay, if we don't iphysically see a break in aer
translocation in them, are there
we can't see at a chromosomal molecular thilevel.ppening that
So if we start going after the
we identify things earlier and genes at the break points, can
with treatments a little bit faster so that we can intervene
So when I looked at these two translocations, there were four
genes of interest.
the PAX5 gene at the chromosome 9 break point, and it had core
binding factor at the chromosome
So my hypothesis was with this 16 break point.
that helped solidify it as a B that this is a translocation
So if this translocation was cell lineage.
like a B cell type abnormality. prAnd then there was a 10-14k
translocation.
had, okay we're good? There were two genes the BMI
gene and then the T cell
So the T cell receptor alpha receptor alpha delta.
clinical probe that we use for delta we see commonly we have a
but if it was in conjunction it involved in T cell disorders,
be just what's fueling the with this BMI-1 gene, could that
So now this is a good hypothesis proliferation.
So we can now take this out of for the step forward.
course with the consent of our the clinical realm and, of
the research realm and really flook at these genes and try to
figure out, make the first step,
genes that are actually involved make sure that those are the
into the research realm to try and then move that out further
these genes in the disease and to figure out how important are
way that they're functioning. So towards that, we were able to
make some FISH probes.
more notch in resolution. And in this one we did see right
off the bat that our T cell receptor has been translocated.
So you see here this is a normal
The five prime end of the gene cell.
gene are together. and the three prime end of the
metaphase. And then over here this is a
chromosome 14 right here, and then you can see the abnormal,
that little tiny chromosome 14, the derivative 14 and then the
derivative 10.
gene is now on chromosome 10. SSo you can see that in bothe
metaphase and in the interphase cells.
So the next question was, well
the translocation, so the question is, is the BMI one gene
also involved?
You can go online and you can find back clones that are
specific to your region of
You can label them up and you can look to see how your clone
reacts in your particular specimen.
So we took this RP11 clone
then we labeled that in blue. thAnd then we looked to see isd
that with the TCR gene at all.
normal 14. And you can see here, here's the
green. So we have the red and the
That's the driver. And here's that derivative 14.
hypothesizing is what's driving the disease, what's making the
proliferation of all of these cells.
And we have the derivative 10 and a normal 10 over here.
So you can see that those markers are there.
So the next question was looking
So what about PAX5 and what about this core binding factor?
It also has been involved in
as well. myeloid disorder translocations
binding factor, this MTG16 is a known culprit in leukemias
already.
these are clones that we So when we look at clones, so
We labeled those up. purchased.
cells, you can see that that And when you hybridize those to
factor are fused in these cells. PAX5 and that core binding
what we're hypothesizing is driving that B cell commitment.s
So now we've take be it to a
handed off for further research, step where now it has to be
it's exciting to have the opportunity to really look into
these disorders more and get
patient questions. more answers to physician and
common site in a clinical So our sgenetics clinic.nd of a
So often what the physicians
lot of developmental delay, no over there see are kids with a
in the door there aren't any real handles, so when they come
practice doctors have. real handles that their family
meeting their milestones, they're having global issues,
but after spending, so the
spend a lot of time asking very specific questions and trying to
get some more answers that might
family practice doctor. nSo in this case we have a a
five-year-old girl, could be any
she's awake at night, very tired young age, with a history of
So her sleep cycles are all off. during the day.
self-injurious behavior. She has a history of
like that. So like head banging and things
So these might be phenotypes And difficulty toilet training.
striking to anybody but coming that really wouldn't be
the physician thought this into a clinical genetics clinic,
syndrome. sSo what comes to us is I would
like to do a FISH test looking
on chromosome 17P. for this very specific deletion
And what you can see here, we have, again, so the control
probe is in green.
as this is chromosome 17. And then you have your region of
interest. So the red probe is for that
Smith-Magenis syndrome region.
that that region is in fact And you can deleted.his patient
So this is a nice case in that
often it's a series of the we're able to get answers, but
So we really need to get better at finding more disorders and
finding efficient ways to get at
So the physician was suspicious of this, but it's important to
get a very distinct clinical
lot of reasons. diSo this opens up access for a
special education opportunities,
There are pharmacological spemanagement options forpy.
regulating that sleep cycle which makes everybody in the
family a lot happier when everybody sleeps at night and
everybody is awake during the day.
Things you learn to appreciate. And then there's surveillance of
very specific things about this syndrome that you would look for
during healthcare maintenance that you might not look for if
you didn't have a very specific diagnosis.
So looking at kidney and thyroid
scoliosis and eye changes. function, monitoring for
highlight how different techniques can be complimentary.
How when you look in one area,
in another area using a little don't find an answer, you look
slightly different resolution you can get the answer that
you've been looking for.
male. The phenotype is developmental
delay, cataract, high myopia, midface hypoplasia, so a very
flattened faces, and
So they have vertebral spondyloepiphyseal dysplasia.
And so this phenotype was very abnormalities.
It was a little bit more severe but it was specific for Stickler
syndrome. And the physician had ordered
sequencing for Stickler syndrome.
So you would think sequencing would find everything.
It would find the mutation, it
looking for. would find exactly what you're
normal. And so the next question was,
okay, well, the phenotype is
expect so let's look at a whole mgenome survey for copy numberd
analysis. So the requested technique was
array comparative genomic hybridization.
So just to give you a very brief
So this is like a giant FISH background of the technique.
So you label your test or your assay.
in green. You label control or reference
DNA in red, and then you
amounts to a microscope slide that has on it spots that are
very specific to all regions of the genome.
So instead of doing, looking at one or two regions of the
genome, we can look at 44,000 plus regions of the genome.
So each of the spots on the slide has lots of little pieces
of DNA. So there are 70 base pair
strings printed in little spots.
patient and your reference DNA So then when you hybridize your
So whatever is in your test tshould be in your control if
everything is normal. And when you have a loss or a
deletion in your patient, you can don't have that labeled
portion in your patient pool. So what you see coming up is
reference.
And these slides, these slides So what you see is red.
eye, they're scanned by a laser and all of that data is put into
a computer and then visually
analysis. rSo in this diagram here with
have the patient has a deletion.
every other area of the genome So what you see is red, and
reference is equal. iSo in this particular patient,s
this is the diagram of what we
computer in the lab. would see coming off of the
you can see that in this patient So this is of chromosome 12 and
chromosome 12. there's a big deletion on
but it includes the gene It's a 2.73 megabase region,
as well as 19 other genes. for Stickler syndrome
help identify the severity. So But with the size of theof
deletion, if you went in and
you sequencing? You're only sequencing the one
allele that's there.
So you would get normal. The other allele is gone.
testing that was already done. So it was a nice complement to
going to talk about really focus So the next few cases that I'm
So we do prenatal diagnosis for more on prognosis.enetics.
So a lot of times we'll get specimens in for advanced
maternal age. So do we see the presence of the
common trisomies that are associated with advanced
maternal age. So 13, 18, 21, sex chromosome
abnormalities.
something, is there a medical Can theintervention.do find
So sometimes there are medical
And then inheritance. So what is the recurrence risk.
So has there been an abnormal ultrasound.
If there's been an abnormal ultrasound, you look at the
genetics, can we see anything that would give the parents any
idea of what recurrence might be.
So this example is one that we
So we have phenotypically normal see often.
So the reason for referral, so potential parents.
a phenotypically normal male, a in partner with a history ofave
miscarriage, that happens often,
pregnancy losses. aSo his mother had multiplee
miscarriages. A partner with an ongoing
pregnancy.
detected by prenatal FISH, where Three copies of chromosome 13
Those types of things. is that extra 13 coming from?
standard chromosome analysis and The requested testing is
And what you can see here on a peripheral blood specimen.
translocation carrier. this patient is a Robertsonian
chromosome? So can you13.l see which
So chromosome 13 has chromosome 14 attached to it head to head.
So this individual has all the
phenotypically normal, but when you try to force his chromosomes
to go through miosis you get
So the reproductive consequences nondisjunction and problems.
affected children, so there's risk of trisomy 13 or 14 in this
particular case.
uniparental disomy. So it's important that you get
the appropriate amount of DNA from mom and the appropriate
amount of DNA from dad. If you don't have that exact
mix, and it is chromosome specific so there are some
chromosomes that are more affected than others, but if you
don't get that mix you can end
because you have too much of up with a phenotypic effect
Even though you have the right your genome that came from mom.
And then what is the risk to number of chromosomes.
So is this translocation new in this individual or did they
inherit it in a balanced fashion
Do they have carrier parents? Are there potential siblings
that might be affected as well? And it also offers the
opportunity for preimplantation genetic diagnosis.
So now if we have a very
look for, we can look for that specific abnormality that we can
increase the chances for a in the preimplantation period to
The next example is, again, a phenotypically normal pregnant
female. The reason for referral is a
fetus with growth retardation.
fast as it should. So the fetus isn't growing as
13, 18, 21, X and Y, so or So the request was for FISH for
there. standard prenatal panel looking
So those are often paired Anbecause the FISH analysiss.
doesn't look for physical rearrangements, it just looks
for presence or absence or too
So we did the prenatal panel. And you can see over here these.
are the probes for chromosome X and 18.
So you can see that this baby is
And then on the right you have a girl.
21. thSo it looks like there's thend
right number of chromosomes, at least with regard to the common
trisomies.
chromosomes, we find too many. When with you look at the
this little extra chromosome. So immediately the technologists
in the lab suspect Emanuel
So this looks like the product syndrome.
common recurrent translocation of an individual who has a
translocation in humans, between that's, like the only recurrent
So when this looks like the derivative 22 from that
translocation.
the banding is not exactly So just to confirm this, because
chromosomes, so we do some extra descript on those tiny
the material on that chromosome testdoes in fact come fromthat
chromosome 11 and chromosome 22.
tests, we do, in fact, see that here we see what's in red is
11Q, so it's that long arm. You have your two normal 11s in
this individual, but then that
material in it. liAnd then when looking for11
chromosome 22, you can see that it also has 22 material.
So it is, in fact, from that
So getting that extra chromosome, in this particular
case, happens because of
So those of you who enjoy looking at segregation, it's
always kind of fun to see how chromosomes can potentially
segregate.
usually happens in a So in this case the segregation
So you end up with that extra derivative chromosome.
So the 11-22 translocation is a recurrent translocation in
humans. The unbalanced segregants are
usually from a three-to-one segregation, leading to 47
chromosomes with that extra derivative chromosome.
So this is just an example, it's
be, but of what the carrier notparent would look like.t to
So they, too, have all the
phenotypically normal, but when you try to force their
chromosomes to go through miosis, to make gametes, things
run amok. And these types of things we see
at a reasonable rate when we do fertility testing, for instance.
So approximately one in 500 people phenotypically normal has
some kind of chromosomal
go undetected, and then for abnfertility reasons they doally
chromosomal work up and we'll find a balanced translocation.
And so then that's an answer
that's where genetic counseling comes in and we talk about what
the possibilities are there.
diagnosis. So the importance of the
like this you can anticipate the So when we see translocations
So in this particular case it's involved with congenital heart
disease.
abnormalities, diaphragmatic They can have kidney
inheritance. hernias, talking about
from? SHow far back can we track it?me
Are there other people who might
And then to really get an idea be at risk?
expectations are. So with a can we do to give this
patient the best that we can? >> What are the diagnoses of
these?
it? >And that's another importanth
thing.
see what's involved with Emanuel So a lot of people go online and
whole list of things. sAny genetic disorder, thea
Internet is really kind of a
That's where you go to your genetic counselors and your
clinical geneticists because
million things because this individual has this genotype,
this individual has this
phenotype. genotype but they also have this
builds, builds but not one So the phenotype kind of builds,
So there can be a whole host of person things to look at.hings.
But really the things that you
case their concerns are with look at are, in this particular
abnormalities. congenital heart disease, kidney
Yeah. So this is a photo that I took
from GeneReviews. So you can go to:
genereviews.org It's a great place to go to get
genetic information, and it just
can describe a phenotype in words but looking at pictures
will really give you an idea of what things can be different in
a phenotype and what things can be the same.
So looking at phenotype in
looking at phenotype in other people is amodels.fferent than
So there are a lot of things
things that you can really point that are different but a lot of
same. And then to try to make those
genotype/phenotype correlations,
the research in human genetics and that's really where a lot of
identify what those genotype/phenotype correlations
are because a lot of times it really isn't well characterized.
But those are the questions.
patients and parents want to Those are the questions that
What can I expect? know.
How can I fix it? And towards that we have to do
more and more work on the abnormalities that we do find to
try to identify gene function,
how it affects development. There's a whole bunch of things
that won't be solved by necessarily...
I have a question.
What are the diagnostics of these types of children?
So these children have
So they have that extra exactderivative 22.ype.
So they're exactly--
So they have the karyotype, if I gocan I go back?o back?
They have this. So when you see Emanuel
syndrome, you will see
But the individuals will look a chlittle bit different becauses.
they all have a different background, but when you look at
just the chromosomes, they'll have the extra derivative 22
from that 11-22 translocation.
So, like I had mentioned before though, too often things are
apparently normal.
done. So we have new mutations to be
discovered, technology costs
So from the clinical laboratory perspective we want to offer our
patients the best and not have
answer. tAnd then to come up with somen
testing algorithms that are really efficient.
So you can, with the tests that are available, they are very
specific. So can we narrow it down faster
and better to get answers for our patients?
So that is all I have this evening.
[APPLAUSE] Thank you
very much.