BIOL-S402F Medical Genetics and Immunology

(Part B: Medical Genetics)

Lecture 11

By Dr. Andy YY CHEUNG

[email protected]
Course outline:
4. Molecular Basis of Genetic Diseases
a. Gregor Mendel and the Laws of Inheritance Lectures 7
b. DNA as the Basis of Inheritance
c. Common monogenic genetic diseases Lectures 8
d. Complex diseases

5. Genetics in Diseases and Development

a. Cytogenetics Lectures 9
b. Common chromosomal abnormalities
c. Epigenetics Lectures 10
d. Mitochondrial DNA inheritance
e. Development and sex determination Lectures 11
f. Clinical genetics and ethical issues
6. Cancer Genetics
a. Genetic factors and environmental factors in cancers
b. Mutations in cell cycle regulatory genes Lectures 12
c. Mutations in the DNA repair system
d. Epigenetics in cancer
Development of human body in 3-dimensions

(Anterior)
(Distal)
(Dorsal)

Proximal

(Ventral) Ds
(Distal)

(Posterior)

Wang K.C. et. al. (2009) Trend Cell Biol. 19(6):268-275.

Human life cycle

Prenatal Period Postnatal Period

2 months 3 months 4months Newborn 2 years 5 years 15 years

Adult
https://www.macmillanhighered.com/BrainHoney/Resource/6716/digital_first_content/trunk/test/hillis2e/hillis2e_ch38_7.html
Human embryo and fetal development (prenatal period)

Germinal
Stage
(0-2
weeks)

Embryonic stage (3-8 weeks)

Fetal stage (9 weeks-birth)
https://img2.pngio.com/human-embryo-and-fetal-development-mind-the-graph-embryo-development-png-800_600.png
Development Fertilization

Trophoblast
(surface layer

from fertilization
Endometrium of cells of the
blastocyst)
Implantation
Endometrium
Blastocoel

to implantation
Inner cell mass

(germinal stage,
Uterine Inner cell
cavity mass

1 DAYS 1–2. The 2 DAY 3. After the 3 DAY 4. By 96 hours, 4 DAY 5. A fluid-filled 5 DAYS 6–7. Some

0-2 weeks)
first cleavage furrow third cleavage, cells
the embryo is a solid cavity called the of the blastocyst’s Actual
extends between the abruptly huddle into a
ball of cells called a blastocoel forms in the surface cells attach size
two polar bodies. compacted ball, and
morula. Cells of the morula and the inner themselves to the
Later cleavage tight junctions among
surface layer will cell mass forms. endometrium and
furrows are angled, the outer cells stabilize.
function in implantation Differentiation occurs start to burrow
so cells become Gap junctions formed
and give rise to a in the inner cell mass into it.
asymmetrically along the interior cells
membrane, the chorion. and gives rise to the Implantation has
arranged. They enhance intercellular
embryo proper. This started.
are loosely communication.
embryonic stage is the
organized with
blastocyst.
space
between them.

Blood-filled spaces Chorion Chorionic

Start of Start of
Chorionic cavity
amniotic embryonic villi
cavity disk
Amniotic
cavity

Connective
tissue

Start of
Start of chorionic cavity Y
yolk o
6 DAYS 10–11. sac
The 7 DAY 12. 8 DAY 14. A connecting
l
yolk sac, embryonic Blood-filled spaces stalk has formed k between
Cummings, M.R. (2010) Human Heredity: disk, and amniotic
cavity have started to
form in maternal
tissue. The chorionic
Actual
size
the embryonic disk and the
s
chorion. Chorionic villi,
Actual
size

Principles and issues. form from the

blastocyst.
Actual
size
cavity starts to
form.
a
which will be features
placenta, start cto form.
of a
Building a baby: The first two weeks
• https://www.youtube.com/watch?
v=9AX1XwKCYQE&list=PLEZmfhKsIZQ5R-
Zj8Zp3nF75RfeFkJjgS&index=6&t
Initiation of
gastrulation

Germinal
Stage
(0-2
weeks)

Embryonic stage
(3-8 weeks)

https://en.wikipedia.org/wiki/Human_embryonic_development
Primitive streak formation
1. Primitive groove
2. Primitive pit
3. Primitive node
4. Oropharyngeal membrane
5. Cardial plate
6. Sectional edge of amniotic
7. membrane
8. Mesoderm
9. Endoderm
10. NB Future cloacal membrane
1+2+3 primitive streak

http://www.embryology.ch/anglais/hdisqueembry/triderm01.html
Trilaminar embryonic disc formation

https://www.invitra.com/en/gastrulation/gastrulation-details/
 Process of human gastrulation

https://biology.stackexchange.com/questions/1145/fetal-development-gastrulation-and-embryonic-disc
General Embryology Review in 20 minutes
• https://www.youtube.com/watch?
v=4YKvVeVMmEE&list=PLEZmfhKsIZQ5R-
Zj8Zp3nF75RfeFkJjgS&index=2
Embryonic Development in Humans
• https://www.youtube.com/watch?
v=dgPCDXmcQjM&list=PLEZmfhKsIZQ5R-
Zj8Zp3nF75RfeFkJjgS&index=3
Sonic hedgehog (SHH)
• Involved in patterning along anterior-posterior axis
• Embryonic development of limbs, somites, gut formation and
establishment of midline CNS
• produced in zone of polarizing activity (ZPA: collection of
mesoderm cells at posterior border of apical ectodermal ridge on
developing limb)
• secreted by notochord to control neural tube patterning
• Mutation in SHH pathway and/or haploinsufficiency can lead
to holoprosencephaly, a developmental defect characterized by a
failure of the early forebrain vesicle to divide into distinct halves
SHH gene
Sonic hedgehog
• The SHH gene provides instructions for
making a protein called Sonic Hedgehog
• This protein functions as a chemical signal
that is essential for embryonic
development
• Sonic Hedgehog plays a role in cell growth,
cell specialization, and the normal shaping
(patterning) of the body
• This protein is important for development
of the brain and spinal cord (central
nervous system), eyes, limbs, and many
other parts of the body
 Sonic hedgehog (Shh)-Patched (Ptch)-Gli
pathway
Fruit fly embryos:

Widtype (WT)

Hedgehog mutant

Human Shh

http://www.signaltonoisemag.com/allarticles/2016/10/21/monstrous-mutations-in-our-
creepy-crawly-friend-the-fruit-fly Turnpenny, P.D. & Ellard S. (2012) Emery’s Elements of Medical Genetics.
Neutral crest migration (Epithelial Mesodermal Transition)
Sonic hedgehog (Shh) gradient from ventral to
dorsal
Dorsal

Shh
Ventral
Notochord

https://en.wikipedia.org/wiki/Sonic_hedgehog#cite_note-1
Nonsyndromic holoprosencephaly (SHH gene
mutations)
• an abnormality of brain development that also affects the head and face
• Normally, the brain divides into two halves (hemispheres ) during early development

• Holoprosencephaly occurs when the brain fails to divide properly into the right and left
hemispheres

https://www.scientistcindy.com/uploads/8/5/1/2/85124478/published/slide23_47.png?1555497522
WNT-7
• Necessary for proper organization along dorsal-ventral axis
• Development of midbrain and limb patterning
• produced at dorsal apical ectodermal ridge (AER: thickened ectoderm
at distal end of each developing limb)
FGF
• Stimulates mitosis and differentiation of underlying mesoderm
• provides for lengthening of limbs by maintaining progress zone
(progress zone: proliferating mesenchymal cells proximal to
AER)
• produced atapical ectodermal ridge
• Controls anterior-posterior neural tube patterning
• Plays a role in somite segmentation, angiogenesis, and axon
growth
Homeobox (HOX) gene
• Involved in segmental organization in cranio-caudal direction
• production depends on combinatorial expression of SHH, WNT-
7, and FGF
• controls rib development, cardiac patterning, and radioulnar
differentiation of the upper extremity
Hox genes

• Hox genes are members of the homeotic

transcription factor family that play a key role in
controlling the body plan along the cranio-caudal
axis
• Hox genes are the master regulators of embryonic
development for all animals, including humans,
flies and worms
• They decide what body parts go where
Hox genes in Drosophila (fruit flies) and humans
5' 3'
Drosophila
8 genes
Abd-B Abd-A Ubx Antp Scr Dfd pb lab

Human being
HOXA
Chr.7p14
A13 A11 A10 A9 A7 A6 A5 A4 A3 A2 A1

HOXB
Chr.17q21
A13 B9 B8 B7 B6 B5 B4 B3 B2 B1
39 genes
HOXC
Chr.12q13
C13 C12 C11 C10 C9 C8 C6 C5 C4

HOXD
Chr.7q31
A D13 D12 D11 D10 D9 D8 D4 D3 D1

Turnpenny, P.D. & Ellard S. (2012) Emery’s Elements of Medical Genetics.

Hox genes contains homeodomain for DNA-
binding and serve as transcription factors

Wang K.C. et. al. (2009) Trend Cell Biol. 19(6):268-275.

Hox gene expressions are regulated by epigentics

Wang K.C. et. al. (2009) Trend Cell Biol. 19(6):268-275.

 Notch-Delta pathway
• Notch itself is a cell-surface receptor that
transduces short-range signals by
interacting with transmembrane ligands
such as Delta (termed Delta-like in
humans) and Serrate (termed Jagged in
humans) on neighboring cells

• The Notch pathway mediates juxtacrine

cellular signaling wherein both the signal
sending and receiving cells are affected
through ligand-receptor crosstalk by
which an array of cell fate decisions in
neuronal, cardiac, immune, and
endocrine development are regulated
 Somatogenesis and Notch-Delta pathway
the process by which germ-cell material develops into body cells

ROSTRAL
All multicellular animals use Notch signaling, which is involved
in the development, maintenance, and regeneration of a
Somites Global somite identity range of tissues
along entire axis
– Hox genes

Segmentation, somite
boundary formation
– Notch-delta, MesP2

Oscillation / cycling gene

Paraxial – Infg
mesoderm
(PS
M)

Specification of PSM identity

– T-box, Fgf8

Tail bud
CAUDAL

Turnpenny, P.D. & Ellard S. (2012) Emery’s Elements of Medical Genetics.

Neural tube defects
• birth defects of the brain, spine, or spinal cord
• They happen in the first month of pregnancy, often before a
woman even knows that she is pregnant
• The two most common neural tube defects are spina bifida
and anencephaly
• The cause is not clear but may be related to genetics,
maternal nutrition (including folic acid deficiency) during
pregnancy

https://healthjade.net/neural-tube-defects/
Neural tube defects
depend on the
location of
defective neural
tube closure

Turnpenny, P.D. & Ellard S. (2012) Emery’s Elements of Medical Genetics.

Brain development in
embryo

Pearson Education (2014)

 Folic acid
• It's critically important to get enough folic acid
because it helps prevent neural tube defects
(NTDs), such as…
• spina bifida (which affects the spinal cord)
• Spina Bifida Occulta
• Anencephaly (which affects the brain)
• Microcephaly

The neural tube is the part of the embryo

from which your baby's spine and brain
develop

https://www.cdc.gov/ncbddd/folicacid/features/folic-acid-helps-prevent-some-birth-defects.html
Pharyngeal (or brachial) apparatus and
craniofacial develoment
Head

Optic vesicle

1
2 Pharyngeal arches
Otic vesicle 3

6 Pericardial bulge

Ectoderm 1 1 First pharyngeal arch

Endoderm
First pharyngeal cleft
2 2
First pharyngeal pouch

Mesenchyme 3 3
Arch artery
4 4
6 6

Turnpenny, P.D. & Ellard S. (2012) Emery’s Elements of Medical Genetics.

Vertebrate limb development (limb bud)
Anterior 1
2
Clavicle Scapula Humerus Radius Metacarpal 3
4
5

Proximal

Distal
Ulna Carpals Phalanges

Posterior
Anterior

Proximal
Stylopod Zeugopod Autopod

Distal
A Posterior B

Limb bud

Proximal
Anterior

Distal
Ectoderm RA

Apical ectodermal ridge

(FGF2, FGF4, FGF8)
AER-FGF
D
Tp63, T-BOX, SALL4

Mesodermal 250 m
core

Proximal Distal

Proximal

Distal
Progress zone
(HoxA, HoxD AER-FGF
WNT7A, GLI, BMP) E
Zone of Posterior Undifferentiated
polarizing activity zone Differentiation
(SHH) front

C Stylopod Zeugopod
Autopod territory territory
territory
Turnpenny, P.D. & Ellard S. (2012) Emery’s Elements of Medical Genetics.
Model for limb bud development

Zellar R. et. al. (2009) Nat

Rev Genet 10(12):845-858.
Drugs/chemicals with a proven
teratogenic effect in humans
Drug Effects

ACE inhibitors Renal dysplasia

Alcohol Cardiac defects, microcephaly,
characteristic facies
Chloroquine Chorioretinitis, deafness
Diethylstilbestrol Uterine malformations, vaginal
adenocarcinoma
Lithium Cardiac defects (Ebstein anomaly)
Phenytoin Cardiac defects, cleft palate, digital
hypoplasia
Retinoids Ear and eye defects, hydrocephalus
Streptomycin Deafness
Tetracycline Dental enamel hypoplasia
Thalidomide Phocomelia, cardiac and ear abnormalities
Valproic acid Neural tube defects, clefting, limb defects,
characteristic facies
Warfarin Nasal hypoplasia, stippled epiphyses

ACE, Angiotensin-converting enzyme

Turnpenny, P.D. & Ellard S. (2012) Emery’s Elements of Medical Genetics.

Teratogens (chemical and physical agents) produce
deformities in embryo and fetus
Fetal
Embryonic stage Defects in physiology;
stage
Germinal stage Major morphological abnormalities physical abnormalities minor

Weeks: 1 2 3 4 5 6 7 8 9 16 20–36 38
Cleavage, Future
implantation heart
Future Future Future Palate
brain eye ear forming

Limb
Teeth External genitalia
buds Central nervous system

Heart

Upper limbs

Eyes

Lower limbs

Teeth

Palate

External genitalia
Insensitivity to
teratogens Ear

Cummings, M.R. (2010) Human Heredity: Principles and issues.

Thalidomide is a cancer drug for
multiple myeloma as teratogen

FIGURE 16.15 A child with thalidomide embry-

opathy. There is absence of the upper limbs
(amelia). The lower limbs show phocomelia
and polydactyly. (Courtesy Emeritus Professor
R. W. Smithells, University of Leeds, UK)

The tragedy was occurred in Europe from 1958 to 1962. In 1961 an association with severe limb anomalies
in babies whose mothers had taken the drug during the first trimester.

Turnpenny, P.D. & Ellard S. (2012) Emery’s Elements of Medical

Genetics.
Co-joined twins are result of incomplete twining during first 2 weeks
• Conjoined twins develop when an early embryo only partially separates to form two
individuals
• Although two fetuses will develop from this embryo, they will remain physically connected —
most often at the chest, abdomen or pelvis
• Conjoined twins may also share one or more internal organs
Two-cell stage

Embryos Embryos Embryos

Chorion Chorion Chorion

Chorion Chorion
Chorion Amniotic Chorion
sac

Amniotic
Amniotic
Figure 3.17 Conjoined twins. Abby and Brittany Hensel
sac
Amniotic Amniotic sac are the result of incomplete twinning during the first 2
sac sac weeks of prenatal development.

a. Identical twins with separate b. Identical twins that share an c. Identical twins that share a chorion
amnions and chorions amnion and chorion but have separate amnions

Lewis, R. (2009) Human Genetics: Concepts and applications.

 Sex determination
and Y chromosome
in human (male)

https://www.ucl.ac.uk/tcga/ScienceSpectra-pages/pics/14-bradman_fig_1.gif
Sex determination (Female) (Ma l e)

and Y chromosome X

in human (male)
Y
Male 44 44
+ +
XX XY

(a) T he XX/XY system

Mechanisms of sex 22 22

determinations in (b) T he XX/XO system

+
XX
+
X

different animals 76
+
ZW
76
+
ZZ

(c) T h e ZW/Z Z s y s t e m

Alligators

males M o s t turtles

males
100 100
%

%
50 50

Cummings, M.R. (2010) Human

0 0 Heredity: Principles and issues.
20 30 40 20
30 40
Temperature (°C)
Temperature (°C)
(d) Sex determination b y temperature
Gene regulatory network in embryonic
gonadal development

Ono M. & Harley V.R. (2013) Nat Rev Endocrinol. 9:79-91.

 • One gene, SRY (for sex-determining region of the Y
chromosome), determines sex in humans
Y chromosome SRY • although many genes are involved, SRY is the key switch
and individuals with SRY develop into males, while those
gene, hormones without it develop into females
testosterone and Indifferent
Undifferentiated
gonads
gonads

dihydrotestosteron Medulla Cortex

e (DHT) determines Wolffian

ducts
XY
(SRY)
XX Müllerian
ducts

the sex organ Testes Ovaries

development
Testosterone MIF Estradiol

5 Inhibition
ti on r ed
mo u ct
P ro a se

Dihydrotestosterone

Internal External External Internal

Turnpenny, P.D. & Ellard S. (2012) male male female female
genitalia genitalia genitalia genitalia
Emery’s Elements of Medical Genetics.
Epididymis Penis Clitoris Fallopian tubes
Seminal vesicles Scrotum Labia Uterus
Vas deferens Distal Proximal vagina
vagina
Differentiation of the
indifferent gonads
of a 5-week embryo
into ovaries or testes

Moore KL & Persaud TVN (2008)

The developing human: clinically
oriented embryology. 8th ed.
 processes by which cholesterol is converted to
Steroidogenesis pathway biologically active steroid hormones

Murphy, C. et. al. (2011) J Pediatr

Adolesc Gynecol. 24:236-250.)
Embryonic differentiation
of female and male
genital ducts from
wolffian and müllerian
primordial tissue before
descent of the testes into
the scrotum

Kronenberg H, et al. (2011) Williams’

textbook of endocrinology.
Human sex differentiation can be
visualized at 8-week embryo
Umbilical cord (lifeline Amnion (a protective, fluid-
between the embryo filled sac surrounding and
and the mother’s tissues) cushioning the embryo)

Lennart Nilsson from A Child Is Born © 1966, 1977, Dell Publishing

Company
Turnpenny, P.D. & Ellard S. (2012) Emery’s Elements of Medical Genetics.
Clinical features of patients with sex
chromosome aneuploidy
Syndrome Karyotype Main clinical features
Turner 45,X Female with retarded sexual development, usually sterile, short stature, webbing of skin
in neck region, cardiovascular abnormalities, hearing impairment, normal
Klinefelter 47,XXY intelligence
deficiency,
Male, infertilelong limbs,
with smallattestes,
risk for
mayeducational
have some problems
breast development, tall, mild mental
Triple X 47,XXX Female with normal genitalia and fertility, at risk for educational and
emotional problems, early menopause
XYY
XXY 47,XYY Tall male with normal physical/sexual development, normal intelligence,
increased
tendency for behavioural and psychological problems

Estrogen Testosterone

XO XX XY XYY

Luthardt, F.W. & Keitges, E. (2001) Encyclopedia of Life Sci , 1–12.

Crossing over between X and Y chromosome pseudoautosomal
region
Y chromosome

http://iws.inha.ac.kr/~biology/lab9/genetics/figure/gene6.jpg
Summary (I)
1. Developmental biology and embryology are the studies of embryo
formation, development of organs to form an organism such as
human;
2. Human formation includes prenatal and postnatal periods;
3. Prenatal period includes three stages: germinal (0-2 weeks), embryonic (3-8
weeks) and fetal (9 weeks-birth) stages;
4. Embryonic stage involves: i.) gastrulation (with heart tube, lung bud and
liver bud), ii.) neurulation and iii.) sex determination (by SRY gene for sex
organ formation);
5. In human, SRY gene in Y chromosome is the key gene to determine the
male gender.
Course outline:
4. Molecular Basis of Genetic Diseases
a. Gregor Mendel and the Laws of Inheritance Lectures 7
b. DNA as the Basis of Inheritance
c. Common monogenic genetic diseases Lectures 8
d. Complex diseases

5. Genetics in Diseases and Development

a. Cytogenetics Lectures 9
b. Common chromosomal abnormalities
c. Epigenetics Lectures 10
d. Mitochondrial DNA inheritance
e. Development and sex determination Lectures 11
f. Clinical genetics and ethical issues
6. Cancer Genetics
a. Genetic factors and environmental factors in cancers
b. Mutations in cell cycle regulatory genes Lectures 12
c. Mutations in the DNA repair system
d. Epigenetics in cancer
Clinical genetics
• involves the study, counselling and
treatment of individuals and families
with heritable disorders and disease
predisposition

• Medical geneticists evaluate, diagnose,

and treat individuals and families with
various genetic indications and/or
specific genetic conditions
Pre-marital check-up in Hong
Kong
FPAHK Pre-marital Check-up provides a wide range of
medical laboratory tests:
Pre-marital & Fertility Preparation Thalassemia, Rubella, Rhesus Factor, and Sexually
Pre-marital Check-up Transmissible Diseases such as Hapatitis B and AIDS.
Pre-pregnancy Check-up
Early Pregnancy
Assessment
• The FPAHK Subfertility Service helps couples who have difficulty in childbearing by
providing clinical assessment, investigation and appropriate treatment.

• Depending on individual case, couples suitable for "Artificial Insemination by Husband"

(AIH) will be offered AIH treatment, which entails stimulation of ovulation by oral drug
followed by intrauterine insemination.

• Others may be referred to the gynaecological clinic or the male infertility clinic at public
or private hospitals for further investigations.
https://www.famplan.org.hk/en/our-services/clinic-services/pre-marital-fertility-preparation/subfertility/content
Clinical Genetic Service, Department of Health
HKSAR
The CGS specialist outpatient clinics (Genetic Counselling Clinic & Genetic Screening
Clinic) Genetic Laboratory and administration office
Hong Kong Children’s Hospital, 1 Shing Cheong Road, Kowloon Bay, HONG
KONG. Phone: 3513 6505 for matters related to Genetic Screening Clinic
Phone: 2725 3773 for matters related to Genetic Counselling Clinic
Patients or families are seen by appointment. A doctor's referral is necessary.

Services provided:
• Genetic Counselling Services
• Genetic Screening Services
• Genetic Laboratory Services
• Genetic Health Promotion Programmes
For private patients, government servants (or Hospital Authority staff) and their dependants,
Appointments can be made in person at:
L-Block Clinic, Queen Elizabeth Hospital, Kowloon, Hong Kong. Phone: 3506 6123

https://www.dh.gov.hk/english/main/main_cgs/main_cgs.html
The CGS specialist outpatient clinics, Department of Health
HKSAR (Genetic Counselling Clinic & Genetic Screening
Clinic)
Any person affected by, or with a family history of the following conditions may attend the
Genetic Counselling Clinic:

 Any known or suspected genetic disorder

 Multiple congenital anomalies / dysmorphism
 Rare / undiagnosed disorders
 Developmental delay / intellectual disability of unknown cause
 Autistic spectrum disorder
 Recurrent abortions of unknown cause
 Suspected sex chromosomal disorders including primary infertility in males and primary
amenorrhoea in females

Clinical Genetic Service Department of Health Leaflet (2019)

Genetic Counselling services are also provided by private hospitals in
Hong Kong

Phone: 2835 7670

email: [email protected]
10/F, Li Shu Pui Block, Hong Kong Sanatorium & Hospital 2
Village Road, Happy Valley, Hong Kong
Clinical Genetics Service
Purpose of Establishing Clinical Genetics Service
1.To provide clinical genetic assessment, diagnosis and counseling to individuals and their families;
2.To promote genetic health for all by way of clinical genetic screening and gene mutation evaluation;
and
3.To disseminate knowledge on genetics among the public and the medical personnel.
•
Scope of Service
Patients and their family members will be advised on proper diagnostic workup by our clinical geneticist
through genetic assessment and counselling. HKSH is equipped with a state-of-the-art genetic
laboratory for a wide array of genetic screenings and tests. Professional teams of the IVF Centre and
other related units are also dedicated to serving patients in need.

Target Group
Any individuals or / and family members: Diagnosed with genetic disease(s)
•Suspected of genetic disease(s)
Abortion Decision?

Prenatal Screening for Down Syndrome

(Source of information provided by the Hospital Authority) (Dec 2019)
This leaflet is intended to help you understand Down syndrome, the
prenatal screening tests for Down syndrome offered by Hospital Authority
(HA), and to help you decide whether you want to have a screening test or
not.

What will happen if the foetus is confirmed to have a genetic

condition?
The doctor will explain to you and your partner about the nature of the genetic
condition, its effect on the foetus and the risk in future pregnancies. You can
discuss with the doctor about available support from the hospitals and other
organizations and be better prepared for the birth of your baby. With specialist
care and education as well as the support from the community services,
children with Down syndrome can live semi-independently. If the pregnancy is
not more than 24 weeks of duration, you may also seek advice from your
doctor about the possibility of termination of pregnancy under the laws in
Hong Kong.
https://
www.fhs.gov.hk/english/health_info/woman/20039.html
 Medical TOP Surgical TOP
Method Drugs are used to stimulate uterine A suction catheter is inserted thro’ the
contraction to expel products of cervix to empty the uterus by vacuum
conception aspiration
Anaesthes Not necessary Local or monitored anaesthesia
ia
Advantage •Surgery and anaesthesia related risks •Needs one visit for TOP and two followups
s are avoided •Higher chance for a complete abortion
•More "natural" process •Shorter duration of bleeding after TOP
Disadvant •Needs two visits for TOP •An invasive procedure
ages •Needs more follow-up visits to confirm •Risks of surgery include cervical or uterine
complete abortion injury, infection, bleeding or intrauterine
•Suction evacuation is needed if the adhesion which may lead to subfertility
abortion is incomplete or fails •Risks of anaesthesia include nausea,
•Complications include infection and vomiting, dizziness, headache, general
heavy bleeding aches & pain
•Side effects of drugs include abdominal •Serious anaesthetic complications include
cramps, fever, nausea, diarrhea and breathing difficulty & suppression, stroke,
allergy heart attack
•Less privacy and autonomy
 in vitro fertilization (IVF) since
1978
• eggs are removed from mature follicles within an ovary
• an egg is fertilized by injecting a single sperm into the egg or mixing the egg with sperm in a
petri dish
• The fertilized egg (embryo) is transferred into the uterus

https://www.bournhall.co.uk/
fertilityblog/ivf-is-40-in-2018-treatment-
continues-improve/
https://
www.bournhall.co.uk/
fertilityblog/ivf-is-40-in-
2018-treatment-
continues-improve/
in vitro fertilization
market in the World

https://visual.ly/
community/
Infographics/health/
global-vitro-
fertilization-ivf-
market-instruments-
reagents-and-media
in vitro fertilization (IVF) current
technology

https://www.news-medical.net/health/Stages-of-IVF.aspx
Frozen embryo, sperms and eggs

https://www.hkarc.com.hk/img/IVF13_en.jpg
Hong Kong Council on Human Reproductive Technology
List of Licensed Centres – Treatment (as at 1 April 2021) (17 nos.)
(Please refer to Appendix for the treatment services provided by individual centres)

Authorized Name of centre

(in alphabetical order)
Assisted Reproductive
Address of premises

Ward 9F, Special Block F, Prince of Wales Hospital, Shatin, N.T

Name of centre
(in alphabetical order)
Prolivfic A.R.T Centre
Address of premises

16/F, New World Tower 2,

organizations
Technology Unit, (IVFHK) Prince
Li Ka Shing O&G Specialist Clinic, Level 2, Prince of Wales Hospital, 18 Queen’s Road, Central, Hong Kong
of Wales Hospital –
The Chinese University of Hong Shatin, N.T. The IVF Clinic Suites 1313, Central Tower, 28 Queen's Road Central, Hong Kong
Kong 1/F & 9/F, Special Block F, Prince of Wales Hospital, Shatin, N.T.
The University of Hong Kong – Rooms 4, 5 and 6, North Wing, 5/F, Tsan Yuk Hospital, 30 Hospital

for IVF
3/F & 5/F, Operation Theatre, Main Clinical Block and Trauma Centre Tsan Yuk Hospital
Road, Sai Ying Pun, Hong Kong
(Extension Block), Prince of Wales Hospital, Shatin, N.T. Preimplantation Genetic
Diagnosis Laboratory
Central Diagnostic Clinic Room 1301, 13/F., Central Tower, 28 Queen's Road Central, Hong
Kong 1-2/F, Main Building, Union Hospital, 18 Fu Kin Street, Tai Wai, N.T.
Union Reproductive Medicine
Centre of Assisted Reproduction K5N, 5/F, Block K, Queen Mary Hospital, Pokfulam Road, Hong Kong Centre
and Embryology, The University of
Hong Kong – Queen Mary Union Reproductive Medicine Unit 1706-07 17/F & Unit 1804-05 18/F Mira Place Tower A, 132
Hospital Centre (Tsim Sha Tsui) Nathan Road, Tsimshatsui, Kowloon
Victory “ART” Laboratory Limited Suite 1412-1425, Prince’s Building, 10 Chater Road, Central, Hong
Department of Obstetrics & Ward 9/F, Block E/F, Prince of Wales Hospital, Shatin, N.T
Kong
Gynaecology, The Chinese Li Ka Shing O&G Specialist Clinic, Level 2, Prince of Wales Hospital,
University of Hong Kong (Prince Shatin, N.T. Victory A.R.T. Laboratory (TST) Room 1101-02, 11/F, 26 Nathan Road, Tsimshatsui, Kowloon
of Wales Hospital)
1/F, Block E/F, Prince of Wales Hospital, Shatin, N.T.

3/F and 5/F, Cancer Centre, Prince of Wales Hospital, Shatin, N.T.
4/F, Block K, Prince of Wales Hospital, Shatin, N.T.
Dr. Stephen CHOW Chun-kay Department of Obstetrics & Gynaecology, 5/F and 10/F, North
Assisted Reproduction Centre,
Kwong Wah Hospital
Wing, Kwong Wah Hospital, 25 Waterloo Road, Kowloon
Section 15(3) of the Human
Hong Kong 1502, Henley Building, 5 Queen's Road Central, Hong Kong Reproductive Technology Ordinance
Assisted
Reproduction (Chapter 561) (“the Ordinance”)
Centre
Hong Kong IVF Centre Limited Suite 1322-1325, 13/F, Ocean Centre, Harbour City, 5 Canton Road,
Tsimshatsui, Kowloon, Hong Kong

Hong Kong Reproductive Suites 1228-30, Ocean Centre, Harbour City, 5 Canton Road,
Medicine Centre Tsimshatsui, Kowloon
Limited
IVF Centre/Obstetrics & IVF Centre, 6/F, Li Shu Pui
Gynaecology Centre,
Hong Kong Sanatorium Block; O&G Centre, 5/F, Li Shu
& Hospital
Pui Block;
Molecular Pathology Laboratory,
G/F and 1/F, Li Shu Fan Block;
Hong Kong Sanatorium & Hospital, 2 Village Road, Happy Valley,
Hong Kong
Pangenia Lifesciences Limited Unit 1380, 13/F, KITEC, 1 Trademart Drive, Kowloon Bay, Kowloon
Next generation sequencing provides tool for
retrieving whole genome information
U.S. DNA testing market, by application, 2012 -
2022 (USD Million)

https://www.grandviewresearch.com/industry-analysis/dna-testing-market
DNA testing in worldwide and Hong
Kong

The company was founded by Linda Avey, Paul

Cusenza and Anne Wojcicki in 2006. In
2007, Google invested $3.9 million in the company,
along with Genentech, New Enterprise Associates, and
Mohr Davidow Ventures. Wojcicki was married to Google
co-founder Sergey Brin at the time.

Circle is wholly owned by Prenetics, a leading global genetic

testing and health technology company, with over USD 50-
million in strategic funding from Alibaba and more.
WHO documents: 1998, 2003 for Medical
Genetics
•WHO. Proposed International Guidelines on Ethical Issues in Medical Genetics
and Genetic Services. Report of WHO Meeting. Geneva: WHO; 1998
(https://apps.who.int/iris/handle/10665/63910)

• WHO. Review of ethical issues in medical genetics. Geneva: WHO; 2003

(https://apps.who.int/iris/handle/10665/68512)
Proposed Guidelines for Pre-symptomatic and Susceptibility
Testing
1. Genetic susceptibility testing of persons with a family history of heart disease, cancer, or
other common diseases of possible genetic origin should be encouraged, provided that
information from the test can be used effectively for prevention or treatment
(beneficence).

2. All susceptibility testing should be voluntary, preceded by adequate information and

based on informed consent (autonomy).

3. Pre-symptomatic testing should be available for adults at risk who want it, even in the
absence of treatment, after proper counselling and informed consent (autonomy).

4. Testing of children or adolescents should be carried out only if there are potential medical
benefits to the child or adolescent or if an adolescent requests it for purposes of
reproductive decision making (autonomy, beneficence).

5. Employers, insurers, schools, government agencies or other institutional third parties should
not be given access to test results (non-maleficence).
Genetic
Counselling
1. Respect for persons and families, including full disclosure, respect for people's
decisions, accurate and unbiased information (autonomy).

2. Preservation of family integrity (autonomy, non-maleficence).

3. Full disclosure to individuals and families of all information relevant to

health (non- maleficence, autonomy).

4. Protection of the privacy of individuals and families from unjustified

intrusions by employers, insurers, and schools (non-maleficence).

5. Information to individuals and families about possible misuses of genetic

information by institutional third parties (non- maleficence).

6. Informing individuals that it is the individual's ethical duty to tell blood

relatives that the relatives may be at genetic risk (non-maleficence).
Genetic Counselling
(continues)
7. Informing individuals about the wisdom of disclosing their carrier status to
spouse/partner if children are intended, and the possibility of harmful effects
on the marriage from disclosure (nonmaleficence).

8. Informing people of their moral duties to disclose a genetic status that may
affect public safety (non- maleficence).

9. Unbiased presentation of information, insofar as this is possible (autonomy).

10. Non-directive approach, except when treatment is available (autonomy,

beneficence).

11. Children and adolescents to be involved in decisions affecting them,

whenever possible (autonomy).
12. Duty to recontact if appropriate and desired (non- maleficence, beneficence,
autonomy).
 Clustered Regularly Interspaced Short Palindromic Repeats
CRISPR technology for gene editing
• a technology that can be used to edit genes
• The essence of CRISPR is simple: it's a way of finding a specific bit of DNA inside a cell
• After that, the next step in CRISPR gene editing is usually to alter that piece of DNA

Jennifer Doudna, PhD, and

Emmanuelle Charpentier, PhD

2020 Nobel Laureates

https://www.gao.gov/products/gao-20-478sp
The “He JianKui ( 贺建奎 ) Incident”: facts and
concerns

The daughters are ”Lulu” and “Nana”.

(a) Infection of target cell

1 CXCR4
or CCR5

CD4
3
ssRNA
https://i.dailymail.co.uk/1s/2019/06/03/15/6742682-7099479- 4
Reverse
This_graphic_reveals_how_theoretically_an_embryo_could_be_edited-a-5_1559572039249.jpg Provirus
transcriptase

• has been found guilty of conducting "illegal medical practices" and sentenced to 3 years in prison.
Summary (II)
1. Genetic counseling is a way for patients and their families to
understand their conditions of the diseases;

2. It involves decision making by the patients and their families such as

risk assessment;

3. The decision should be taken by the patients and their families but not
the others;

4. Genetic testing should be kept in piracy and should not be a tool to

screen their employees, students and clients from the companies or
schools;

5. Due to advances of technologies and social acceptability of technologies

changing from time to time, the ethic issues should be reviewed from
time to time to make benefits for patients and the societies.
78