Genetics

Question 1

What is Autosomal Dominant Inheritance?

Answer 1

• Heterozygous for the dominant allele;
• On each pregnancy an affected individual has 50% chance of passing it;
• Homozygous (2 copies of the dominant allele) is rare.

Question 2

Give examples of Autosomal Dominant Inheritance?

Answer 2

• Huntington’s disease
• Polycystic kidney disease
• Neurofibromatosis

Question 3

What is Autossomal recessive inheritance?

Answer 3

• Both parents MUST be carriers (only one copy) or have the disease themselves (two copies);
• The trait (disorder) can only manifest when 2 copies of the gene (one from each parent) are inherited.

Question 4

Give example Autossomal recessive inheritance conditions?

Answer 4

• Cystic fibrosis
• Sickle cell anaemia
• Thalassemia
• Congenital adrenal hyperplasia
• Haemochromatosis
• Wilson’s disease

CATCH WILSON
Cystic fibrosis
Anaemia (sickle cell)
Thalassemia
Congenital adrenal hyperplasia
Haemochromatosis
Wilson’s

Question 5

Autosomal recessive with both parents being carriers (they don’t have the disease). What are the chances of an affected child?
Ex: cystic fibrosis

Answer 5

• 25% chance of an affected child
• 50% chance of a child being a carrier
• 25% chance of a child who doesn’t have the disease and is not a carrier.

Question 6

What is X-linked recessive inheritance?

Answer 6

• Disorders that are caused by mutations in genes on the X chromosome;
• Males only have a single X chromosome and if affected that is all that is needed to cause the disease;
• Females require 2 copies of X chromosome to fully express the disease (since it’s recessive);
• On a female if only one X affected is passed, she becomes a carrier

Question 7

Examples of X-linked recessive inheritance? Sim

Answer 7

• Haemophilia A
• Duchenne muscular dystrophy
• G6PD deficiency

Question 8

What are the chances of having an affected child in X-linked recessive inheritance?
- Father doesn’t have the disease;
- Mother is a carrier.

Answer 8

• There is a 25% chance of having a boy affected
• 25% chance of having a female carrier.

Question 9

A couple is expecting a boy. The mother is a carrier for haemophilia A. The father doesn’t have the disease.
- What are the chances of an affected child?

Answer 9

X-linked recessive inheritance
- 50 %
- Because it already says it’s a boy.
- There is 50% chance of having a healthy boy and 50% chance of an affected child.

Question 10

A couple is expecting a baby. The father has haemophilia A. The mother is normal.
- What are the chances of an affected child?

Answer 10

X linked recessive inheritance
- There is 0% chance of an affected child.
- 50% chance of the child being a carrier
- All females will be carriers
- All boys will be unaffected and won’t be carriers.

Question 11

Example of X linked dominant inheritance.

Answer 11

• Fragile X syndrome.

Question 12

A 25 yo woman just gave birth. Her father (the grandparent) has Huntington’s disease. She hasn’t been tested and doesn’t present any symptoms.
- What are the chances of the baby being affected?

Answer 12

• Huntington’s is autosomal dominant.
• The woman has a 50% chance of being affected.
• Her baby has half her chances so 25% chance of being affected.
• If you knew for sure that the mother of the baby was affected, than the baby would have had 50% chance of being affected. Since it’s not known the status of the mom (she could be affected or not have the gene) than the baby has 25% chances.

Question 13

Describe the autosomal dominant pedigree chart.

Answer 13

• Every affected person has at least one affected parent.
• Both males and females can be equally affected.
• Trait does not skip generations.
• Approximately half of the offspring of an affected person, are affected.
• Unaffected individual do not pass the trait.

Question 14

Describe the autosomal recessive pedigree chart.

Answer 14

• Affected individuals often have unaffected parents (parents will be carriers only);
• It can skip generations;
• Approximately 25% of offspring are affected when both parents are carriers;
• All children of two affected parents are affected;

Question 15

Describe the X-linked recessive pedigree chart.

Answer 15

• More males are affected than females;
• No male to male transmission (dad’s can only give Y chromosome to their sons);
• Affected males often have unaffected parents (happens when the mother is the carrier).
• All daughters of affected males are carriers (males can only pass the affected X chromosome);
• Half the sons of carrier females are affected.

Question 16

Describe the X-linked dominant pedigree chart.

Answer 16

• Both males and females can be affected;
• No male-to-male transmission;
• Affected fathers will have all affected daughters;
• Traits do not skip generations.

Question 17

A child has cystic fibrosis.
What are the chances of the grandfather (paternal) being a carrier?

Answer 17

• Cystic fibrosis is autosomal recessive.
• For the child to be affected both parents HAVE to be carriers. Hence it is confirmed that the dad is a carrier since the child is affected.
• The grandfather has a 50% chance.

Question 18

What will be the chances of inheritance of sickle cell anaemia if:
- One parent is homozygous (for sickle);
- The other parent is heterozygous (for sickle).

Answer 18

• 50% chances of offspring being affected;
• 50% chances of offspring being carriers.

Question 19

What are the investigations done in Duchenne muscular dystrophy?

Answer 19

Initial test: creatinine kinase

Others
- Muscle biopsy
- Genetic testing (after +ve biopsy)

Question 20

DDx between:
- Duchenne muscular dystrophy
- Becker muscular dystrophy

Answer 20

- Both x-linked recessive

Duchenne
- Onset of symptoms by age 3
- Diagnosis between 4-8 years.

Becker
- Later onset of symptoms (16 years)

Question 21

What are the congenital defects associated with Down syndrome?

Answer 21

• Atrioventricular septal defect
• Duodenal atresia

Question 22

What are the symptoms of DiGeorge Syndrome?

Answer 22

CATCH-22

• Cardiac abnormalities
• Abnormal face
• Thymic aplasia (absent)
• Cleft palate
• Hypocalcaemia/Hypoparathroidism
• Chromosome 22 abnormalities

Question 23

What are the symptoms of Angelman syndrome?

Answer 23

Neonatal period:
- Normal head circumference;
- Developmental delay signs by 6 months;

Childhood period:
- Severe developmental delay;
- Disproportionate head circumference growth.

Question 24

What are the features of Klinefelter syndrome?

AKA: 47 XXY

Answer 24

• Affects males only

G-FELTER
- Gynecomastia
- Facial hair (low)
- Estrogen is ⬆︎ and testoterone is ⬇︎
- Long limbs
- Tall and slim
- Elevates FSH and LH
- Rage (agressive behaviour)

Hypogonadism
- Small testes
- Azoospermia (no sperms in semen)
- Infertility

Question 25

How is the **diagnosis** of `Klinefelter` `syndrome` done?

Answer 25

Karotyping - chromossome analysis 47 XXY.

Question 26

What are the `symptoms` of **Huntington's disease**?

Answer 26

- `Autossomal dominant / Family Hx` - Changes of personalities - Self neglect, clumsiness - `Memory loss` - Poor concentration - `Chorea (jerky involuntary movements)` - Dystonia - Rigidity - Dementia ➜ **Symptoms in next generation appear earlier and earlier.**

Question 27

Describe how **investigation for potential genetic diseases** is done?

Answer 27

**Before pregnancy:** - Preimplantation genetic diagnosis (in vitro) **After pregnancy:** `➜ Week 11-14 (late 1st trimester)` - Chorionic villus sampling (placenta testing) `➜ Week 15-18 (early 2nd trimester)` - Amniocentesis (amniotic fluid tested)

Question 28

What is the **prenatal test** done in `sickle cell anaemia`?

Answer 28

**1st line:**`Maternal haemonoglobinapathy` - To test if the mother carries the sickle cell trait. - If the test is positive than CVS or amniocentecis can be done.

Question 29

What is the **mode of inheritance** for `BRCA1 gene mutation`?

Answer 29

Autosomal dominant with incomplete penetrance.

Question 30

What is the **gene mutation** associated with **`MEN`** `breast cancer and prostate cancer`?

Answer 30

BRCA2.

Question 31

What are the features of **Alport syndrome**?

Answer 31

- X-linked disease - Haematuria + Proteinuria - End stage renal disease - Sensorineural hearing loss - Eyes abnormalities

Question 32

What is the `gene associated` with **`Diabetes`** and **`coeliac disease`**?

Answer 32

HLA-DQ2.