Genetic

Testing,
Prenatal
Genetic
Diagnosis
and
Preimplantation
Genetic
Diagnosis
ClinicalLaboratory
Perspectives
and
Ethical
Issues
Involved
Teguh
Haryo
Sasongko,
MD,
PhD
Human
Genome
Center,
School
of
Medical
Sciences
Universiti
Sains
Malaysia
Lecture
for
Undergraduate
Study
in
Medicine
Bioethics
and
Health
Law
4
Faculty
of
Medicine
and
Health
Sciences
Universitas
Jenderal

Soedirman
Purwokerto,
12
January
2012

KOTA
BHARU
KOTA
BHARU

Tujuan
Pembelajaran
Genetic
Testing
(GT)
,
Prenatal
Genetic
Diagnosis
(PND)
,
Preimplantation
Genetic
Diagnosis
(PGD)
Mahasiswa
mampu
menjelaskan
definisi
dan
perbedaan
antara
GT,
PND
dan
PGD
Mahasiswa
mampu
menjelaskan
indikasi
klinis
dan
metodemetode
laboratorium
dalam
melakukan
GT,
PND
dan
PGD
Mahasiswa
mampu
menjelaskan
implikasi
etik,
hukum
dan
sosial
atas
informasi
genetika
pada
manusia

Mahasiswa
mampu
mengidentifikasi
dan
menganalisa
permasalahan
etik
yang
berkaitan
dengan
privasi
dan
kerahasiaan
informasi
genetika
manusia
Mahasiswa
mampu
mengidentifikasi
dan
menganalisa
permasalahan
etik
yang
berkaitan
dengan
pengambilan
keputusan
klinis
atas
hasil
GT,
PND
dan
PGD

Beware!
Science
does
mislead

During
the
development
of
an
individual,
genes
influence
not
only
bodily
features
at
microscopic
and
macroscopic
levels
and
the
metabolic
and
physiologic
condictions
underlying
medical
health,
but
also
the
etheral
aspects
of
human
nature,
including
emotions,
psychologies,
personalities,
and
even
ethical
and
religious
predilections

Mathematics
1+
1=
2
Bioethics
1+
1=
1+
1
1+
1
D>
D
1+
1

Chromosome;
Gene;
DNA
Gene
is
a
segment
of
DNA
Gene
1
that
is
involved
in
producing
a
polypeptide
chain;
It
can
include
regions
preceding
and
following
the
coding
DNA
as
well
as
Gene
2
introns
between
the
exons;
It
is
considered
a
unit
of
heredity
Allele
:
one
of
two
or
more

different
versions
of
a
gene
www.
genome.
gov;
www.wordnetweb.
princeton.
edu

C
r
m
s
o
m
l
D
i
s
o
r
e
r
s

h
o
o
a

(Down
Syndrome,
Patau
Syndrome,
Klinefelter
Syndrome,
Fragile
X
Syndrome,
Cri
du
Chat
etc)
Singlegene
Disorders
(Thalassemias,
Cystic
Fibrosis,
Spinal
Muscular
Atrophy,
Duchenne
Muscular
Dystrophy,
Tuberous
Sclerosis
Complex,
Arginase
Deficiency etc)
Multifactorial
Disorders/Conditions
(Hypertension,
Diabetes
Mellitus,
Other
Cardiovascular
Diseases,
Schizophrenia;

Skin
Color,
Hair
color,
Height
etc)

www.
genome.
gov

www.
genome.
gov

www.
genome.
gov

Genetic
Testing

Test
to
identify
genetic
cause
or
risk
factor
for
a
disease
Done
based
on
clinical
diagnosis
Methodologies
:
1.
Chromosomal
aberrations
(number
and
structure)
:
Karyotyping
and
Fluorescence
Insitu
Hybridyzation
(FISH)
2.
Gene
aberrations
(point
mutations,
deletions,
insertions)
:
PCR,
PCRRFLP,
DHPLC,
HRMA,
MLPA
DNA
Sequencing

Genetic
Testing

Purpose
:
1.
To
confirm
clinical
diagnosis
prognosis
and
treatment
2.
To
identify
inheritance
risk
2.
To
predict
risk
of
having
multifactorial
disorder

Genetic
Testing
in
Human
Genome
CenterUSM

Cyto-Molecular
(
Chromosome)
Analyses
:
Down,
Edward,
Patau,
Klinefelter,
Fragile
X,
Turner,
Prader-Willi,
DiGeorge,
Recurrent
Miscarriages
Molecular
(
Gene)
Analyses
:
Ambiguous
Genitalia
(
Sex-Determining
Region
Y
SRY)
Spinal
Muscular
Atrophy
(
SMA
SMN1)
Duchenne/
Becker
Muscular
Dystrophy
(
DMD/
BMD

Dystrophin)
Gilbert
Syndrome
(
UGT1A1)
Beta-Thalassemia
(
Beta-Globin)

Karyotyping
for
Down
Syndrome
(Trisomy
21)

FISH
for
DiGeorge
Syndrome

Ambiguous
Genitalia
A
birth
defect
where
the
outer
genitals
do
not
have
the
typical
appearance
of
either
a
boy
or
a
girl
http:
/
/
www.
nlm.
nih.
gov/
medlineplus/ency/
arti
www.
dshs.
state.tx.
us/
newborn/
cle/
003269.
htm

SRY
Gene
1
2
3
4
5
1
DNA
ladder
2
Control
with
SRY
absent
3
Control
with
SRY
present
4
Patient
5
Water
PCR
Y

Duchenne/Becker
Muscular
Dystrophy
Inherited
Muscular
Dystrophy
Most
Severe
form
of
MD
Progressive
Muscle
Weakness
Xlinked
recessive
1:
3500
males
Caused
mostly
by
exonic
deletions
of
Dystrophin
gene
Dystrophin
79
exons;
the
largest
gene
in
human

MLPA
for
DMD/
BMD

xqcon
73
14
54
34
74
15
55
35
Exons
Control
Patient

Prenatal
Genetic
Diagnosis

Test
to
identify
genetic
cause
of
a
particular
human
genetic
disorder
before
birth
Done
based
on
existence
of
risk
or
screening
of
common
disorders;
highrisk
pregnancy
Methodologies
:
Same
as
Genetic
Testing
Specimen
Sampling
:
Aminiocentesis,
Chorionic
Villus
Sampling

to
obtain
DNA
or
chromosomes

Prenatal
Genetic
Diagnosis
in
Human
Genome
Center
USM

Prenatal
Genetic
Diagnosis;
Benefits

Prenatal
Diagnosis
for
Prognosis
Prediction

Sasongko
et
al.
,
2010

Preimplantation
Genetic
Diagnosis

Test
to
identify
genetic
defects
in
embryos
created
through
invitro
fertilization
(IVF)
before
implantation
Done
based
on
existence
of
risk
or
chromosomal
screening
for
aneuploidy
Methodologies
:
Same
as
genetic
testing
Specimen
Sampling
:
Embryo
Biopsy
postfertilization;
few
cells
biopsied
to
obtain
DNA
or
chromosomes

Preimplantation
Genetic
Diagnosis

Purposes
:
1.
To
avoid
selecting
embryos
with
genetic
defects;
successful
pregnancy
2.
To
match
HLA
type
potential
organ/
tissue
donor
3.
To
avoid
embryos
with
high
cancer
predisposition
4.
Sex
Selection
5.
6.
7.
8.

ELSI
Ethical,
Legal
and
Social
Implications

Genetic
Information
Eugenics
Establishing
Diagnosis

ELSI
Ethical,
Legal
and
Social
Implications

Why
would
YOU
bother
?

Genetic
Information
What
is
genetic
information
?
Genotype
Others
(epigenetic,
transcriptomic,
proteomic
)
Environmental
Factors;
Lifestyle;
Diet
PHENOTYPES

Central
Dogma
of
Molecular
Biology

Categories
of
Genetic
Information
Nonsensitive
information
Observable
information
Private
information
Sensitive
information

Issues
with
Privacy

Who
owns
your
genetic
information
?
Who
have
access
to
your
genetic
information
?
Misuse
and
Discrimination
Health
Insurance
Employment
Use
other
than
those
stated
in
informed
consent

Issues
with
Privacy

Eubios
Ethics
Institute,
A
Cross
Cultural
Introduction
to
Bioethics,
2005

Eugenics

Any
effort
to
interfere
with
individual s
procreative
choices
in
order
to
attain
a
societal
goal
Prenatal
Genetic
Diagnosis
Preimplantation
Genetic
Diagnosis
Ensuring
Good
Breeding
?
Eliminating
Genetic
Disorders
?

Eugenics

Eubios
Ethics
Institute,
A
Cross
Cultural
Introduction
to
Bioethics,
2005

21
10
6
21
10
6
Would
you
consider
PND
for
the
next
pregnancy
?
YES
NO
Unsure
Sasongko
and
Zabidi-Hussin,
2011
(
unpublished)

If
the
test
turned
up
positive;
What
then
?

20
1
Abort
Not
Abort
Sasongko
and
Zabidi-Hussin,
2011
(
unpublished)

Issues
when
establishing
diagnosis

Chromosomal
Aberration
Straightforward
Variable
Severity
Issues
with
PND
Singlegene
defect
Straightforward
Multifactorial
Disorder
Is
genetic
testing
alone
enough
?
Complications
with
Incidental
Finding
of
Nonpaternity
Case
1
BThalassemia
Case
2
BThalassemia
Both
parents
identified
to

have
First
son
identified
of
having
compound
heterozygous
mutation
of
codon
41/
42
heterozygous
of
IVS2654
and
codon
17
Fetus
identified
to
have
compound
mutation
heterozygous
of
codon
41/
42
mutation
Mother
identified
of
having
heterozygous
and
codon
17
mutation
IVS2654
Father
does
not
have
any
mutation
Li
and
Liao,
2008

Disease
Labeling

Legal
Instruments

UNESCO s
Universal
Declaration
on
the
Human
Genome
and
Human
Rights,
1997
Malaysia:
DNA
Identification
Act
No.
699,
2009
The
Philippines
Rule
on
DNA
Evidence
US:
Genetic
Information
Non-discrimination
Act
(GINA)
,
2008

Matur
Nuwun
Thank
You,
Terima
kasih
tghsasongko@gmail.
com
teguhhs@kk.
usm.
my
+
60129874175
Matur
Nuwun
Thank
You,
Terima
kasih
tghsasongko@gmail.
com
teguhhs@kk.
usm.
my
+
60129874175