Case 13- mechanism of inheritance

Question 1

Homozygous dominant inheritance

Answer 1

AA x aa –> A A a a –> Aa, Aa, Aa, Aa –> 100% heterozygous. All offspring will develop the dominant phenotype.

Question 2

One Heterozygous dominant inheritance

Answer 2

Aa x aa –> A a a a –> Aa, Aa, aa, aa –> 50% heterozygous, 50% homozygous recessive. Half of the offspring will develop the dominant phenotype.

Question 3

2 Heterozygous recessive inheritance

Answer 3

Aa x Aa –> A A a a –> AA, Aa, Aa, aa –> 25% homozygous dominant, 50% heterozygous, 25% homozygous recessive. 25% will develop the recessive phenotype.

Question 4

Homozygous x Homozygous inheritance

Answer 4

AA x aa –> A A a a –> Aa, Aa, Aa, Aa –> 100% heterozygous. None of the offspring will develop the recessive phenotype but they will all be carriers.

Question 5

1 Heterozygous recessive X-linked disease

Answer 5

(X^A x Y) x ( X^A x X^a) –> ( X^A x X^A), ( X^A x X^a), ( X^A x Y) (X^a x Y) –> 50% of males will have the disease, 50% of males wont have the disease and 50% of the females will be carriers. Overall, 25% of offspring get the disease.

Question 6

Two Homozygous recessive X-linked disease

Answer 6

(X^A x X^a) x (Y x X^a) –> (X^A x X^a), (X^a x X^a), (X^A x Y), (X^a x Y) –> 50% of males will have the disease, 50% of males will not have the disease, 50% of females will be carriers and 50% of females will have the disease. Overall, half of all offspring will have the disease.

Question 7

Why do X-linked diseases affect more men

Answer 7

If the disease is fatal to males it is unlikely that they will live long enough to pass on their genes. This means females are less likely to get the disease as they need two copies of the gene. However, men can get it from female carriers.

Question 8

Inheritance of mitochondrial DNA

Answer 8

1) It is passed down the maternal line
2) Mutations can form in the mitochondrial DNA
3) During meiosis there is uneven assortment of DNA, some egg cells may contain more mutated DNA and some may contain less
4) During embryo development mutated mitochondrial DNA can divide and become more prominent
5) One child may have 50% mutated mitochondrial DNA and have a severe disease whilst another child may only have 25% mutated mitochondrial DNA and have a mild disease.

Question 9

Penetrance

Answer 9

Penetrance of an inherited disease is the proportion of people who have a particular mutation who go on to develop the disease.

Question 10

Expressivity

Answer 10

Variability in the signs/symptoms a particular individual may experience

Question 11

What influences Penetrance

Answer 11

1) Link between gene and disease, some diseases have a 100% penetrance.
2) Environmental factors/lifestyle
3) Age- Huntington’s is late onset, people may die before they get the disease

Question 12

Disease which does not have full penetrance

Answer 12

The BRCA1 gene increases your risk of breast cancer

Question 13

Diseases which have different levels of expressivity

Answer 13

Marfan syndrome as there are variable signs and symptoms. It is a connective tissue disorder

Question 14

Why do we use family trees?

Answer 14

• Records family history.
• Build a pattern of inheritance.
• Aids diagnosis /investigation /management.

Question 15

Key rules for family trees

Answer 15

• Use conventional symbols
• 3 generations
• Mark affected/ unaffected/ carrier
• Include abortions/miscarriages
• Indicate individuals seeking advice

Question 16

Male symbol

Answer 16

Square

Question 17

Female symbol

Answer 17

Circle

Question 18

Partners symbol

Answer 18

Connected by line

Question 19

Separated symbol

Answer 19

Diagonal line through the straight line connecting the partners

Question 20

Un-identical twins symbol

Answer 20

Upside down V

Question 21

Identical twins symbol

Answer 21

Triangle

Question 22

Consultant symbol

Answer 22

Arrow pointing

Question 23

Proband symbol

Answer 23

First individual with disease. Arrow pointing with P in the corner

Question 24

With disease symbol

Answer 24

Filled in

Question 25

Carries (not likely to get disease) symbol

Answer 25

Dot in the middle

Question 26

Carriers (asymptomatic or presymptomactic) symbol

Answer 26

Line through the centre

Question 27

How to arrange the family tree

Answer 27

For partners males on the left and females on the right. For siblings eldest on the left and youngest to the right

Question 28

Miscarriage or abortion symbol

Answer 28

Small triangle

Question 29

Symbol to indicate death

Answer 29

Put a diagonal line through the person. Add the age they died on the side as well as cause

Question 30

How to denote close relations between partners i.e. distant cousins

Answer 30

Two horizontal lines between them

Question 31

Examples of mitochondrial disease

Answer 31

Includes Leber’s Hereditary Optic Neuropathy (LHON) and LHON plus. Leigh’s disease. Pyruvate Dehydrogenase Complex deficiency (PDCD/PDH).

Question 32

Characteristics of Mitochondrial disease

Answer 32

Can only be passed down the maternal line. If a male has a mitochondrial disease he can not pass it on to his children. Another may not pass the mitochondrial disease to all of her children, it depends how much of the mutated mitochondrial DNA ends up in each egg cell.

Question 33

Diseases with a dominant pattern of inheritance

Answer 33

1) Huntington’s disease
2) Marfan syndrome
3) Neurofibromatosis
4) Achondroplasia

Question 34

Huntington’s disease

Answer 34

Mutation in the Huntington gene. Causes disruption in the control of movement as nerve cells die in a region of the brain which controls movement. This causes Choreiform movement. Degenerative disease which gets worse over time. Delayed onset, symptoms occur at 40/50 but gets earlier in subsequent generations. Continuous movement. Dominant inheritance

Question 35

Marfan syndrome

Answer 35

Due to Fibrillin deficiency. A connective tissue disorder which leads to thin individuals with elongated fingers (Arachnodactyly). Increased risk of Dissecting aortic aneurysms. Dominant inheritance

Question 36

Neurofibromatosis

Answer 36

An NFI gene mutation. Dysregulation of RAS which is a tumour suppressor, leads to multiple neufibromas (tiny bumps). It is a disorder of the nervous system affecting development of nerve cell tissues. There is an increase tumour risk. Dominant inheritance

Question 37

Achondroplasia

Answer 37

Lack of bone growth. A mutation in a growth factor receptor gene. Causes dwarfism. Dominant inheritancr

Question 38

List of diseases with a recessive pattern of inheritance

Answer 38

1) Cystic fibrosis
2) Thalassaemia
3) Phenylketonuria
4) Hartnups disease

Question 39

Cystic fibrosis

Answer 39

An autosomal recessive disease. A mutation in the CFTR gene resulting in a disruption in sodium/chloride movement. Causes sticky mucus and salty sweat.

Question 40

Thalassaemia

Answer 40

It is autosomal recessive, there are alpha and beta types. Alpha Thalassaemia involves two genes HBA1 and HBA2. Beta thalassaemia has one gene HBB.

Question 41

Phenylketonuria

Answer 41

Is autosomal recessive due to a mutation in Phenylalanine hydroxylase. Body can not metabolise the amino acid Phenylalanine. Causes mental disability and a mousy smell as the brain does not receive enough amino acids and becomes damaged, the phenylalanine clogs up the amino acid transporters in the brain. The smell is due to the body trying to metabolise the phenylalanine, the products then produce this smell.

Question 42

Hartnups disease

Answer 42

Is autosomal recessive and is due to a defect in uptake of neutral amino acids. Results in the malabsorption of Tryptophan. Causes Pellagra (skin rash). Uncontrolled can cause problems in the brain.

Question 43

Disease with an X-linked pattern of inheritance

Answer 43

1) Haemophilia A
2) Haemophilia B
3) Colour blindness
4) Duchenne muscular dystrophy

Question 44

Haemophilia A

Answer 44

A factor VIII deficiency. A blood clotting disorder. Leads to haemorrhage and longer PTT. X linked disease.

Question 45

Haemophilia B

Answer 45

A factor IX deficiency, blood clotting disorder. Leads to haemorrhage and longer PTT. X linked disease

Question 46

Colour blindness

Answer 46

A mutation of opsin pigment in the cones of the retina. Depending on which genes it can lead to red-green or blue-yellow colour blindness. X linked disease.

Question 47

Duchenne muscular dystrophy

Answer 47

A mutation for the gene dystrophin. A muscle wasting disease, which affects muscle which connects cytoskeleton’s to the basal lamina. Muscle weakening and muscle wasting. X linked disease. Degenerative.