Transcript Ante and Postnatal Screening

Ante- and Postnatal Screening
https://www.twigonglow.com/film/b
irth-936/
https://www.youtube.com/watch?v
=DZsZ9vXFx04
Learning Intentions
• Explain the use of antenatal care screening to
identify risks and potential disorders
• Describe antenatal screening techniques used
– ultrasound, biochemical testing, diagnostic
testing, rhesus antibody testing and PGD
Antenatal Care
• During pregnancy the mother is closely
monitored. This includes checks on the
mother’s :
blood pressure
blood type
blood and urine
general health
Antenatal Care
• An example of a potential complication that
each assessment might reveal is:
 height and weight - obesity;
 blood pressure - hypertension;
 blood tests - diabetes;
 urine tests - renal failure;
 medical history - cystic fibrosis
Antenatal Screening
• Antenatal screening is carried
out to monitor the health of a
pregnant woman and her
fetus
• Antenatal screening identifies
the risk of a disorder so that
further tests can be carried
out and a prenatal diagnosis
can be given
Screening Vs Diagnostic Tests
Screening Test
• A screening test detects signs and symptoms
associated with a disorder
• A degree of risk can be assessed
Diagnostic test
• A diagnostic test is a definite test which establishes,
without doubt, whether a person is suffering from a
specific condition or disorder
Methods of Antenatal Screening
• Ultrasound imaging
• Biochemical tests
• Diagnostic testing
• Rhesus antibody testing
Video
Ultrasound
• Dating scans (done at 8-14
weeks) give information
about the stage of gestation
and the due date.
• Anomaly scans (done at 1820 weeks) take a close look
at the fetus and the uterus.
They can detect serious
physical problems
• Tests for marker chemicals
which vary normally during
pregnancy are used with
dating scans
Fetus at 12 weeks
Biochemical Tests
• Biochemical tests are used to
detect the normal physiological
changes of pregnancy through
blood and urine samples
• Changes can detect complications
eg in the condition pre-eclampsia
the concentration of urea in the
plasma is significantly higher than
normal and concentration of
calcium in the urine is significantly
lower
Markers
• At 16 – 18 weeks the pregnant woman is offered a
series of biochemical tests that check for different
chemical markers.
• Medical conditions can also be detected by a range
of marker chemicals that indicate a condition but
need not necessarily be part of the condition.
Markers
• For example, the
marker Human
Chorionic
Gonadotrophin
normally HCG increases
during weeks 6-10 then
decreases to a steady
low level
• However, it remains
high if the foetus has
Down’s syndrome
False Positives and Negatives
• Measuring a substance at
the wrong time could lead to
a false positive or false
negative result
• For example, HCG results at
10 weeks could give a false
positive and would be
meaningless since both a
normal pregnancy and a
Down’s pregnancy would
show elevated results at
week 10
Diagnostic Tests
They are carried out:
• If routine screening has indicated an increased
risk of a condition
• for individuals already in high risk categories
(eg women over 35)
• If there is a family history of a harmful genetic
disorder
Risks of Diagnostic Testing
• 2 main types of diagnostic testing are:
Amniocentesis
Chorionic Villus Sampling (CVS)
• Both amniocentesis and CVS increase the risk
of miscarriage
• In deciding to proceed with these tests, the
element of risk associated with the tests must
be assessed by the parent(s)
Amniocentesis
• Amniocentesis is carried out at
about 14-16 weeks of pregnancy
• A small amount of amniotic fluid is
withdrawn and this contains foetal
cells
• The cells are cultured to produce a
karyotype, this usually takes about
2 weeks
• A karyotype is a visual display of a
person’s complete chromosome
complement, arranged in pairs
Normal Karyotypes
Down’s Syndrome
• A karyotype containing an extra copy of chromosome 18 indicates
Edward’s Syndrome
• The condition is characterised by unusual skull shape and small
chin. The sufferer also has heart and kidney malformations
• Very few sufferers live beyond their first year and have profound
delay in all aspects of development
• It occurs in 1 in 3000 live births
Chorionic Villus Sampling (CVS)
• This involves taking a
sample of placental cells
• The cells are cultured and
used for karyotyping
• Has an increased risk of
miscarriage compared to
amniocentesis but it can
be carried out earlier - as
early as 8 weeks into
pregnancy and allows
immediate karyotyping
Rhesus Antibody Testing
• Generally mothers show no
immune response to their
fetus although sensitisation
to rhesus antigens can occur.
• This can happen when a
rhesus negative mother is
first pregnant with a rhesus
positive fetus and a mixing of
blood at birth occurs causing
sensitisation of the mother to
rhesus antigens
Rhesus Antibody Testing
• The immune system of the
mother then makes anti-rhesus
antibodies and memory cells
• A second rhesus positive fetus
will be attacked through the
placenta by the anti-rhesus
antibodies from the mother
• The fetus can be given saved by replacing the rhesus positive
blood with rhesus negative via a transfusion
• Or the mother can be injected with anti-rhesus antibodies, just
after the birth of the first child, this destroys the rhesus antigen
PGD
• Pre-implantation genetic diagnosis (PGD) is used to
identify eggs with genetic disorders. It is available to
couples, in conjunction with IVF, that are at risk of
having a child with a specific genetic or chromosome
disorder.
Learning Intention
• Describe the use of post-natal screening using
PKU as an example
Phenylketonuria (PKU)
The amino acid phenylalanine is found in the diet.
enzyme C
enzyme A
phenylalanine
enzyme B
Intermediate
metabolites
melanin
(Skin pigment )
tyrosine
(an amino acid)
In a PKU sufferer the gene that codes for enzyme 1 is
defective – what will this result in?
Phenylketonuria (PKU)
enzyme C
melanin
enzyme A
phenylalanine
enzyme B
Intermediate
metabolites
tyrosine
(an amino acid)
Phenylalanine builds up in the blood .
(Skin pigment )
Phenylketonuria (PKU)
• PKU is an autosomal recessive inherited metabolic
disorder.
• Phenylalanine builds up in the blood and causes
mental development to be restricted
• It is fairly common in the UK – about 1 in 10,000 live
births.
• PKU is routinely tested for in newly born babies using
a Heel prick test.
• PKU can be treated by following a low
phenylalanine diet
Phenylketonuria (PKU)
Sufferers usually have a lighter skin pigment than
normal, but will not be albino as some tyrosine will be
present in their diet and this can re-instate the end of
the pathway so some melanin is still made.
enzyme C
enzyme B
tyrosine
(an amino acid)
Intermediate
metabolites
melanin
(Skin pigment )
Albinism
• Albinos cannot make
enzyme C and are
therefore unable to
make melanin.
• This protein is the dark
pigment in skin and
other organs, including
the retina
Learning Intention
• To revise genetic definitions and genetic
crosses
What can you remember
about genes, inheritance
and genetic crosses?
Definitions Revision
1.
2.
3.
4.
5.
Haploid
Diploid
Alleles
Recessive
Dominant
6. Homozygous
7. Heterozygous
8. Genotype
9. Phenotype
10. Gene
Monhybrid Cross Revision
Use the following genes and symbols
• T = tall plants, t = dwarf;
• G = grey body flies, g = black;
• R = tongue roller, r = non roller;
Draw out a punnett square and work out ratios of
phenotypes for the following crosses
a) Tt x Tt
b) Rr X rr
c) Gg x Gg
d) Gg x gg
e) Rr x Rr
a) Tt x Tt
T
t
T
TT
Tt
t
Tt
tt
r
r
R
Rr
Rr
r
rr
rr
1 roller : 1 non roller
3 tall : 1 dwarf
c) Gg x Gg
G
g
G
GG
Gg
g
Gg
gg
3 grey : 1 black
b) Rr x rr
e) Gg x gg
g
g
G
Gg
Gg
g
gg
gg
1 grey : 1 black
f) Rr x Rr
R
r
R
RR
Rr
r
Rr
rr
3 rollers : 1 non roller
Learning Intention
• Explain the use of pedigree charts to analyse
patters of inheritance in genetic screening and
how these could be used in counselling
Pedigree Chart
Pedigree Charts and Counselling
• Pedigree charts (family trees) are used to analyse
patterns of inheritance in genetic screening
• Once the phenotype for a characteristic is known and
a family tree is constructed most of the genotypes
can be determined
• This information is used by
genetic counsellors to
advise parents of the
possibility of passing on a
genetic condition to their
child
Different Patterns of Inheritance
•
•
•
•
Autosomal recessive
Autosomal dominant
Autosomal incomplete dominance
Sex linked recessive trait
Remember X and Y chromosomes are sex
chromosomes. All other chromosomes are
called autosomes.
William Bateson and patterns of inheritance
Learning Intention
• Describe the pattern of autosomal recessive
inheritance
Autosomal Recessive Inheritance
• The trait is:
– Expressed relatively
rarely
– May skip generations
– Males and females
equally affected
– All sufferers
homozygous recessive
– Non-sufferers
homozygous dominant
or heterozygous
Ryan’s story
Female sufferer of cystic
fibrosis
Male non-sufferer of cystic
fibrosis
Autosomal Recessive Inheritance
A = normal b= cystic fibrosis
What is the probability of
these parents’ children having
cystic fibrosis?
0%
Autosomal Recessive Inheritance
A = normal b= cystic fibrosis
What is the probability of
these parents’ children having
cystic fibrosis?
25%
There is an autosomal blood
disorder in which a faulty form
of haemoglobin is produced.
The allele for normal
haemoglobin (H) is dominant to
the allele for faulty
haemoglobin (h).
What is the genotype of person
a) 1 in 1st generation
hh
a) 4 in 2nd generation
Hh
Learning Intention
• Describe the pattern of autosomal dominant
inheritance
Autosomal Dominant Inheritance
• Males and females
affected equally
• All non sufferers
homozygous recessive
• Sufferers homozygous
dominant of
heterozygous
Luke’s story
Female sufferer of
Huntingtons
Male non-sufferer of
Huntingtons
Autosomal Dominant Inheritance
B = Huntington’s Disease
sufferer
b = normal
What is the probability of these
parents’ children having
Huntington’s?
50%
Learning Intention
• Describe the pattern of autosomal incomplete
dominance inheritance
Incomplete Dominance
• So far we have looked at
situations where autosomal
alleles are either dominant or
recessive
WW
• In some cases dominant allele
does not fully express itself, this
is known as incomplete
RW
dominance
RR
RW
RW
RW
RW
Incomplete Dominance
When writing out a incomplete dominance
cross, both alleles have capitals and a different
letter.
WW
RR
P
F1
RW
RW
RW
RW
RW
Incomplete Dominance
If red and a white short flowers are crossed, the
offspring appear pink.
Parents (P)
Red
RR
R
R
x
W
RW
RW
White
WW
W
RW
RW
All F1 offspring are pink.
Incomplete Dominance
If pink flowers were crossed with one another,
what proportions of colours would you expect in
the F2 generation? (Use a punnet square)
x
Sickle Cell
• Haemoglobin S is much less
efficient at carrying oxygen
than normal haemoglobin.
• People who are homozygous
for the abnormal allele
(SS) suffer from the
condition sickle cell anaemia.
• People who are homozygous
for the normal allele (HH)
produce normal haemoglobin
and normal red blood cells.
Sickle Cell
• People who are heterozygous
(HS) do not suffer from sickle
cell anaemia, but from a milder
condition known as the sickle
cell trait.
• Heterozygotes possess a
phenotype 'in-between' the two
homozygous phenotypes. In
other words the normal allele
is incompletely dominant to
the sickle cell allele.
Tamilore’s story
Autosomal Incomplete Dominance
• The fully expressed form of
the disorder occurs relatively
rarely
• Partially expressed form
occurs more frequently
• Males and females equally
affected
Autosomal Incomplete Dominance
• Non sufferers are
homozygous for one
incompletely dominant allele
• Sufferers of the fully
expressed form of the
disorder are homozygous for
the other incompletely
dominant allele
• Sufferers of the partly
expressed form are
heterozygous for the two
alleles
Learning Intention
• Describe the pattern of sex linked recessive
inheritance
Sex linkage
• The X chromosome is larger than the Y
• As a result the X chromosome carries
more genes
• Genes which are carried on the same
sex chromosome are said to be sexlinked.
• Use X and Y to represent the sex
chromosomes, and superscript letters
to represent the alleles eg. XR Xr
Sex Linked Recessive
If being colour blind is recessive, cross a male colour
blind with a female with colour vision who is a non
carrier
XbY
Xb
XBXB
XB
Y
Y
XB
XB
XBXb
(1)
XBY
(2)
XBXb
(3)
XBY
(4)
(1)
(2)
(3)
(4)
XB
Female with normal colour vision
Male with normal colour vision
Female with normal colour vision
Male with normal colour vision
Sons get the Y from their dad, therefore they
must inherit the disease from their mother
Daughters have to get the recessive gene from
both parents to inherit the condition
Sex Linked Recessive
• Sufferers of the trait are
homozygous recessive,
normally male XhY
• Non sufferers are
homozygous dominant XHY
XHXH or are heterozygous
female carriers XHXh – they
don’t suffer form the
condition but carry a copy of
the. gene which thay can
pass on to their offspring
Carrier
mother
Carrier
daughter
Sex Linked Recessive
• Many more males are
affected than females
• None of the sons of an
affected male show the
trait
• Some of the grandsons of
an affected male do show
the trait
Carrier
daughter
Carrier
daughter