Ante- and Postnatal Screening

https://www.twigonglow.com/film/birth-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 typeblood and urinegeneral 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 18-20 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.

• 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

Markers

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:AmniocentesisChorionic 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)

enzyme Aenzyme B

phenylalanine tyrosine

(an amino acid)

melanin

(Skin pigment )

enzyme C

Intermediate

metabolites

In a PKU sufferer the gene that codes for enzyme 1 is defective – what will this result in?

The amino acid phenylalanine is found in the diet.

phenylalanine

enzyme B

tyrosine

(an amino acid)

melanin

(Skin pigment )

enzyme C

Intermediate

metabolites enzyme A

Phenylalanine builds up in the blood .

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)

enzyme B

tyrosine

(an amino acid)

melanin

(Skin pigment )

enzyme C

Intermediate

metabolites

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.

Phenylketonuria (PKU)

• 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

Albinism

Learning Intention

• To revise genetic definitions and genetic crosses

What can you remember about genes, inheritance

and genetic crosses?

Definitions Revision

1. Haploid2. Diploid3. Alleles4. Recessive5. Dominant

6. Homozygous7. Heterozygous8. Genotype9. Phenotype10. Gene

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 Ttb) Rr X rrc) Gg x Ggd) Gg x gge) Rr x Rr

Monhybrid Cross Revision

T t

T

t

TT Tt

Tt tt

3 tall : 1 dwarf

r r

R

r

Rr Rr

rr rr

1 roller : 1 non roller

G g

G

g

GG Gg

Gg gg

3 grey : 1 black

a) Tt x Tt b) Rr x rr

c) Gg x Gg

g g

G

g

Gg Gg

gg gg

1 grey : 1 black

R r

R

r

RR Rr

Rr rr

3 rollers : 1 non roller

e) Gg x gg

f) Rr x Rr

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

Female sufferer of cystic fibrosis

Male non-sufferer of cystic fibrosis

Ryan’s story

Autosomal Recessive Inheritance

A = normal b= cystic fibrosis

What is the probability of these parents’ children having cystic fibrosis?

0%

Autosomal Recessive Inheritance

25%

A = normal b= cystic fibrosis

What is the probability of these parents’ children having cystic fibrosis?

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 persona)1 in 1st generation

a)4 in 2nd generationhh

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

Female sufferer of Huntingtons

Male non-sufferer of Huntingtons

Luke’s story

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

• In some cases dominant allele does not fully express itself, this is known as incomplete dominance

WW RR

RW RW RW RW RW

Incomplete Dominance

When writing out a incomplete dominance cross, both alleles have capitals and a different letter.

WW RR

RW RW RW RW RW

P

F1

Incomplete Dominance

If red and a white short flowers are crossed, the offspring appear pink.

Parents (P) Red x White RR WW

W WR RW RWR 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

• 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

Autosomal Incomplete Dominance

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 sex-linked.

• Use X and Y to represent the sex chromosomes, and superscript letters to represent the alleles eg. XR Xr

If being colour blind is recessive, cross a male colour blind with a female with colour vision who is a non carrier

XbY XBXB

XXbb YY XXBB XXBB

XXBBXXbb

(1)(1)XXBBYY(2)(2)

XXBBXXbb

(3)(3)XXBBYY(4)(4)

XX bb YY

XXBB

XXBB

(1) Female with normal colour vision(2) Male with normal colour vision(3) Female with normal colour vision(4) 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

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