Higher Human Biology Unit 2 – Physiology and Health Section 12 – Antenatal and Postnatal Screening https://www.twigonglow.com/film/birth-936/

What Can You Remember? What is meant by continuous and cyclical fertility? Describe the process of artificial insemination What is the purpose of super-ovulation? Describe the process of ICSI Describe the process of IVF What is PGD? Name two barrier methods of contraception What is female tubal ligation?

a – Antenatal Screening We will be learning… To state that a variety of techniques can be used to monitor the health of the mother, developing baby and foetus Describe the technique of antenatal screening as the process that identifies the risk of a disorder so that further tests and diagnosis can be offered. Explain the use of ultrasound for dating the foetus and to identify abnormalities. Describe the diagnostic chemical tests that are carried out to monitor the concentrations of marker chemicals Describe the process of diagnostic testing such as amniocentesis and chronic villus sampling. State the advantage and disadvantage of amniocentesis and chronic villus sampling techniques. That a significant number of cells can be sampled and cultured in order to obtain a karyotype in order to diagnose a range of conditions.

Antenatal “before birth” Screening Antenatal screening is carried out to monitor the health of a pregnant woman and her foetus Antenatal screening identifies the risk of a disorder so that further diagnosis tests can be carried out and a prenatal diagnosis can be given

Antenatal “before birth” Screening This consists of: Ultrasound for dating Ultrasound for detecting abnormalities Diagnostic chemical testing – marker chemicals Amniocentesis Chronic villus sampling

Hypertension (High Blood Pressure) Antenatal Care During pregnancy the mother is closely monitored. This includes checks on the mother’s : Antenatal Test Condition Blood Pressure Hypertension (High Blood Pressure) Medical History Cystic Fibrosis Height and Weight Obesity Blood Tests Type/Diabetes Urine Tests Renal Failure

Ultrasound Ultrasound is used to create images of soft tissue structures, such as the gallbladder, liver, kidneys, pancreas, bladder, and other organs and parts of the body.  Ultrasound can also measure the flow of blood in the arteries to detect blockages. Ultrasound imaging uses sound waves to produce pictures of the inside of the body. It is used to help diagnose the causes of pain, swelling and infection in the body's internal organs and to examine a baby in pregnant women and the brain and hips in infants. Foetus at 12 weeks

Ultrasound – for Dating Dating scans (done at 8-14 weeks) give information about the stage of gestation and the due date. Tests for marker chemicals which vary normally during pregnancy are used with dating scans

Ultrasound – for Detecting Abnormalities Anomaly scans (done at 18-20 weeks) take a close look at the foetus and the uterus. They can detect serious physical problems

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

Diagnostic Biochemical Testing Biochemical tests are used to detect the normal physiological changes of pregnancy through blood and urine samples e.g. HCG Changes can detect complications e.g. in the condition pre-eclampsia (high blood pressure) 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 https://www.webmd.com/baby/video/amniocentesis

What is a Karyotype? A Karyotype allows a doctor to see the number and visual appearance of the chromosomes in the cell nuclei of an organism or species. To make a karyotype, scientists take a picture of the chromosome from one cell, cut them out, and arrange them using size, banding pattern, and centromere position as guides.

Normal Karyotypes of Males and Females To make a karyotype, scientists take a picture of the chromosome from one cell, cut them out, and arrange them using size, banding pattern, and centromere position as guides.

Amniocentesis Advantages Disadvantages The test determines if there are any genetic or chromosomal abnormalities. It can identify hundreds of genetic disorders such as Down’s Syndrome, Edwards syndrome and Tay-Sachs disease. It is the only test that can provide results that are accurate. It can determine if the babies lungs are healthy if the baby is going to be born prematurely. Disadvantages Risk of miscarriage – this depends on the skill of the doctor Risk of uterine infection following the procedure

Down’s Syndrome Trisomy 21 are quite noticeable—a round face and upturned eyes, and a short, stocky build, for example. People with Down syndrome sometimes move awkwardly, usually due to low muscle tone (hypotonia) at birth that can interfere with physical development.

Edward’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

Turner’s Syndrome only one X chromosome instead of two A karyotype with an X chromosome missing indicates Turner’s syndrome Individuals affected in this way are always female and short in stature Since their ovaries do not develop, they are infertile and fail to develop secondary sexual characteristics at puberty It occurs with a frequency of 1 in 2500 female live births

Klinefelter’s Syndrome A karyotype with two X chromosomes and a Y indicates Klinefelter’s syndrome The affected individual is always male and possesses male sex organs They are infertile because their testes are very small and fail to produce an sperm Occurs with a frequency of about 1 in 1000 male 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 https://www.youtube.com/watch?v=sxEf_ddmpZk

Chronic Villus Sampling Advantages Possibility of performing the procedure during the first trimester of pregnancy which means a relatively fast result - CVS is usually done between 10 and 13 weeks of pregnancy. Results are usually available 7 days after the procedure. Highly accurate Disadvantages risk of miscarriage comparable to that in case of amniocentesis

Rhesus Antibody Testing Generally mothers show no immune response to their foetus although sensitisation to rhesus antigens can occur. This can happen when a rhesus negative mother is first pregnant with a rhesus positive foetus and a mixing of blood at birth occurs causing sensitisation of the mother to rhesus antigens https://www.youtube.com/watch?v=pwKqwcVNuMY

Rhesus Antibody Testing The immune system of the mother then makes anti-rhesus antibodies and memory cells A second rhesus positive foetus will be attacked through the placenta by the anti-rhesus antibodies from the mother The foetus can be 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

b – Genetic Screening and Counselling We will be learning… To draw, analyse and interpret patterns of inheritance through genetic screening and counselling To describe patterns of inheritance in autosomal recessive, autosomal dominant, incomplete dominance and sex-linked recessive single gene disorders

Genetic Screening This is the study of a person's DNA in order to identify genetic differences or susceptibility to particular diseases or abnormalities.

Genetic Counselling the giving of advice to prospective parents concerning the risks of genetic disorders in a future child Carrier identification e.g. carrying risk of disease Prenatal diagnosis Forensic screening e.g. paternity testing

What can you remember about genes, inheritance and genetic crosses?

Definitions Revision Haploid Diploid Alleles Recessive Dominant Homozygous Heterozygous Genotype Phenotype Gene

Monohybrid 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 Tt x Tt Rr X rr Gg x Gg Gg x gg Rr x Rr

a) Tt x Tt b) Rr x rr r r T t R Rr Rr T TT Tt r t rr rr Tt tt 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

g g G Gg Gg g gg gg 1 grey : 1 black R r R RR Rr r Rr 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

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 A genetic counsellor may recognise: 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.

Autosomal Recessive Inheritance Female sufferer of cystic fibrosis The trait is: Expressed relatively rarely May skip generations Males and females equally affected All sufferers homozygous recessive Non-sufferers homozygous dominant or heterozygous Male non-sufferer of cystic fibrosis

Autosomal Recessive Inheritance X and Y chromosomes are Sex Chromosomes All others are known as Autosomes Cystic Fibrosis is an example of autosomal recessive inheritance Sufferers are homozygous recessive, cc Non sufferers are homozygous dominant or heterozygous (CC or Cc) Cystic fibrosis results from a 3 base pair deletion on chromosome 7 – this produces a non functional protein

Deletion on chromosome 7 Mucus is found at various sites in the body These sites include the lungs, the pancreas and the alimentary canal The mucus produced by sufferers of cystic fibrosis becomes thicker and stickier than normal The organs become congested and blocked The frequency, in GB, of being a carrier is 1 in 25 Genetic counsellors use this information during genetic screening

Autosomal Recessive Inheritance A = normal a= cystic fibrosis What is the probability of these parents’ children having cystic fibrosis? 0%

Autosomal Recessive Inheritance A = normal a= cystic fibrosis What is the probability of these parents’ children having cystic fibrosis? 25%

What is the genotype of person 1 in 1st generation 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 1 in 1st generation 4 in 2nd generation hh Hh

Autosomal Dominant Inheritance Female sufferer of Huntingtons Males and females affected equally All non sufferers homozygous recessive Sufferers homozygous dominant of heterozygous Male non-sufferer of Huntingtons

Autosomal Dominant Inheritance - Huntington’s Chorea Huntington’s Chorea is an example of autosomal dominant inheritance The trait appears in every generation Each sufferer of the trait has an affected parent When a branch of the family does not express the trait, the trait fails to reappear in future generations of that branch Males and females are affected in approximately equal numbers All non sufferers are homozygous recessive, hh All sufferers are HH or Hh

Cause and Prognosis From previous study, in unit 1, we know that Huntington’s disease is caused by an affected gene on chromosome 4 The type of mutation involved results in the codon CAG being repeated more than 35 times Lack of correct protein leads to: Premature death Decreased production of neurotransmitters Progressive degeneration of the central nervous system

Autosomal Dominant Inheritance B = Huntington’s Disease sufferer b = normal What is the probability of these parents’ children having Huntington’s? 50%

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

Incomplete Dominance When writing out an incomplete dominance cross, both alleles have capitals and a different letter. WW RR P F1 RW RW RW RW RW

All F1 offspring are pink. Incomplete Dominance If red and a white short flowers are crossed, the offspring appear pink. Parents (P) Red x White RR WW W R RW All F1 offspring are pink.

Incomplete Dominance x 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.

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

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

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 XBXB Xb Y XB XB 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 XBXb (1) XBY (2) (3) (4) Y Xb XB XB

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 they 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

Haemophilia A protein called Factor VIII is required for the blood clotting Haemophilia (blood does not clot or takes a very long time to clot) is caused by a recessive gene which is carried on the X chromosome H represents normal blood clotting and h represents haemophilia Colour blindness and haemophilia are rare in females since two recessive alleles must be inherited

Haemophilia Genotype Phenotype XH XH Normal female XH Xh ‘Carrier’ female Xh Xh Haemophiliac female XH Y Normal male Xh Y Haemophiliac male

c – Postnatal Screening We will be learning… To describe the processes involved in postnatal screening. Describe the diagnostic test for phenylketonuria (PKU) Explain how PKU is treated

Post Natal Screening New-born screening is a public health program of screening in infants shortly after birth for a list of conditions that are treatable, but not clinically evident in the new-born period.

Diagnostic Test for PKU Phenylketonuria (PKU) is a rare genetic disorder that is present from birth. In PKU, the body is unable to break down an amino acid called Phenylalanine which then builds up in the blood and in the brain and can cause problems when untreated. The treatment for PKU is effective.  It involves a protein restricted diet for life and taking regular dietary supplements which contain amino acids, vitamins and minerals.  The aim is to keep the blood Phenylalanine level within a specific target range. A PKU test is done a day or two after your baby's birth. The test is done after your baby is 24 hours old and after your baby has ingested some protein in the diet to ensure accurate results. A nurse or lab technician collects a few drops of blood from your baby's heel or the bend in your baby's arm.

Phenylketonuria (PKU) The amino acid phenylalanine is found in the diet. enzyme C melanin (Skin pigment) Intermediate metabolites enzyme B enzyme A phenylalanine 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 B tyrosine (an amino acid) melanin (Skin pigment) enzyme C Intermediate metabolites enzyme A phenylalanine 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) 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 melanin (Skin pigment ) Intermediate metabolites enzyme B tyrosine (an amino acid)

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

Now I can….. a – Antenatal Screening State that a variety of techniques can be used to monitor the health of the mother, developing baby and foetus Describe the technique of antenatal screening as the process that identifies the risk of a disorder so that further tests and diagnosis can be offered. Explain the use of ultrasound for dating the foetus and to identify abnormalities. Describe the diagnostic chemical tests that are carried out to monitor the concentrations of marker chemicals Describe the process of diagnostic testing such as amniocentesis and chronic villus sampling. State the advantage and disadvantage of amniocentesis and chronic villus sampling techniques. State that a significant number of cells can be sampled and cultured in order to obtain a karyotype in order to diagnose a range of conditions.

b – Genetic Screening and Counselling Now I can….. b – Genetic Screening and Counselling Draw, analyse and interpret patterns of inheritance through genetic screening and counselling Describe patterns of inheritance in autosomal recessive, autosomal dominant, incomplete dominance and sex-linked recessive single gene disorders

c – Postnatal Screening Now I can….. c – Postnatal Screening To describe the processes involved in postnatal screening. Describe the diagnostic test for phenylketonuria (PKU) Explain how PKU is treated

Chronic Villus Sampling (CVS) Word Meaning Allele form of a gene coding for a version of a characteristic Amniocentesis prenatal test to assess health of foetus using cells from amniotic fluid Anomaly Scan antenatal ultrasound scan that checks for physical abnormalities Antenatal Screening use of tests to identify risk of a disorder before birth Autosomal Dominant allele on chromosomes 1-22; always expressed in phenotype Autosomal Recessive allele on chromosomes 1-22; expressed in phenotype if the genotype is homozygous for the recessive allele Chronic Villus Sampling (CVS) prenatal test to assess health of the foetus using cells from the placenta Embryo stage of development up to about 8 weeks that leads to the formation of a foetus Feotus stage of a baby after 8 weeks of development Heterozygous having two different alleles of the same gene Homozygous having two identical alleles of the same gene

Rhesus Antibody Testing Word Meaning Incomplete Dominance when an allele is not completely masked by a dominant allele, thus affecting an individual's phenotype Karyotype display of matched chromosomes produced for medical purposes Pedigree Chart diagram showing the occurrence of phenotypes of a particular gene in a family tree Phenylketonuria metabolic disorder that is tested for by postnatal screening Postnatal Screening diagnostic testing of newborn babies Prenatal Diagnosis identification of the risk of sisorders in unborn babies Rhesus Antibody Testing testing to show if a person carries rhesus antibodies in their blood Sex-linked Recessive recessive allele carried on the X chromosome Ultrasound Scanning diagnostic procedure used for various prenatal checks, such as establishing the stage of pregnancy and the date that the baby is due

Give an account of the tests which can be carried out once a woman has been confirmed as pregnant, under the headings: screening tests; (6 marks) diagnostic tests. (4 marks)

Screening tests (maximum of 6 marks): Screening indicates possibility of a condition. Ultrasound dating scan at 8-14 weeks indicates age of foetus / likely due date. Ultrasound anomaly scan at 18-20 weeks indicates possible unusual development, associated with e.g. Down's syndrome. Biochemical tests on blood samples. Levels of marker chemicals inappropriate to stage of pregnancy, e.g. α- foeto protein indicate possible presence of Down's syndrome. Diagnostic tests (maximum of 4 marks): Diagnostic tests confirm the presence of condition. Amniocentesis removes cells from the amniotic fluid and are carried out at about 18 weeks Chorionic villus sampling removes cells from the placenta and are carried out at 10-12 weeks. Karyotyping - examination of foetal chromosomes.

HHB Specimen 2018 Question 8 B

HHB Specimen 2018 Question 9

HHB Specimen 2018 Question 13 A

HHB 2018 Question 12 D