Inheritance Patterns

Question 1

Describe a Pedigree drawing

Answer 1

• Males are squares
• Females are Circles
• Partners have a line between them
• Siblings have a line above them
• Line down for children
• Affected people are shaded
• Carriers have dots in them

Question 2

What is meant by autosomal dominant?

Answer 2

• Autosomal means that the “gene” in question is located on one of the chromosomes
• Dominant means that a single copy of the mutated gene is enough to cause the disorder

Question 3

State the features of an autosomal dominant disorder

Answer 3

• Mostly present in Heterozygous form
• Affects multiple generations
• Affects both sexes
• Male to female transmission and vice versa
• usually comes from affected parents
• 50% risk to offspring

Question 4

Features of dominant inheritance
Describe Incomplete/reduced penetrance

Answer 4

Where some people have the mutation but do not have the disease. The disease is not displayed.

Question 5

Features of dominant inheritance
Describe variable expressivity

Answer 5

Variation in the severity/symptoms of the disorder between different individuals with the same mutation

Question 6

Features of dominant inheritance
Describe De novo mutation rate

Answer 6

Not all affected individuals have an affected parent.
Usually depends on the severity of the disorder. Can vary greatly between conditions.

Question 7

Features of dominant inheritance
Describe Mosaicism

Answer 7

Where the mutation is only present in a proportion of cells

Question 8

Features of dominant inheritance
Describe Anticipation

Answer 8

Where the disease worsens in severity in successive generations. E.g. Expansion disorders

Question 9

Define the term “Penetrance”

Answer 9

Percentage of individuals who carry the mutation AND develop symptoms of the disorder
- Many dominant disorders show age dependent penetrance

Question 10

What is meant by the term “recessive”?

Answer 10

Recessive means that two copies of the mutated gene is required to cause the disorder.

Question 11

Describe Autosomal Recessive disorders

Answer 11

• Usually present in the homozygous/compound heterozygous forms
• Carriers are not affected
• Both sexes are affected
• Male to female transmission and vice versa
• Usually one generation affected
• May be consanguinity

Question 12

State the features of compound heterozygous
Give an example

Answer 12

Compound heterozygote
- 2 mutations in the same gene
- Mutations are different

Cystic fibrosis
•∆F508
•G542X

Question 13

State the features of a Compound Homozygous

Answer 13

Homozygote
- 2 mutations in same gene
- Identical mutations

Cystic fibrosis
•∆F508
•∆F508
- May suggest consanguinity

Question 14

Describe features of autosomal recessive inheritance

Answer 14

• The trait is often found in clusters of siblings but not in parents or offspring.
• Recurrence risk = 1/4 for each sibling of affected person
• Carrier probability = 2/3 for unaffected siblings of affected person
• All offspring of affected person are obligate carriers

Question 15

What Chromosome pairs do females have?

Answer 15

Females have two X chromosomes
- Can be homozygous or heterozygous

Question 16

What chromosome pairs do males have?

Answer 16

Males have one X and a Y chromosome
- Hemizygous

Question 17

How can X linked inheritance be recessive?

Answer 17

• Females are carriers + unaffected
• No male to male transmission

Question 18

How can X linked inheritance be dominant?

Answer 18

• Females are affected
• Males more severely affected/lethal

Question 19

What are the features of X linked recessive inheritance?

Answer 19

• X linked genes are never passed from father to son
• All daughters of affected males are obligate carriers
  -The offspring of female carriers have a 50% chance of inheriting a mutant allele

Question 20

Features of X-linked recessive inheritance
Describe Skewed X-inactivation

Answer 20

Generally random but 10% of females have uneven or skewed X inactivation

Question 21

Features of X-linked recessive inheritance
Describe Manifesting carriers

Answer 21

Some females have some symptoms in X linked recessive conditions e.g. cardiomyopathy in DMD.

Question 22

Describe Y linked inheritance

Answer 22

Always and only passed from fathers to sons

Question 23

Define the term mutation

Answer 23

A change in the genetic material

Question 24

What does a pathogenic mutation result in?

Answer 24

Results in an alteration of the function of the gene product and can cause a disease phenotype

Question 25

What are the 3 different types of mutations?

Answer 25

- Substitution - Deletions - Insertions

Question 26

Where are these mutations found?

Answer 26

- Coding DNA - Non coding DNA (such as promoters and introns)

Question 27

What is the impact of amino acid substitution?

Answer 27

- Large chemical similarity between the two amino acids - functional role of the specific domain of the protein may be similar - Phylogenetic conservation of original amino acid amongst diverse species