Pedigree

Question 1

What is pedigree?

Answer 1

Visual representation of a family
- Used to study single gene disorders

Question 2

If both parents are carriers of a AR gene what are the chances of the child being being homozygous recessive (affected by disease)?

Answer 2

25%

Question 3

If the mother comes from a population with a 1/50 chance of being a carrier of disease and the father a 1/100 what are the chances that both parents are carriers?

Answer 3

(1/50) * (1/100) = 1/5,000

Question 4

If the mother comes from a population with a 1/50 chance of being a carrier of a Recessive disease and the father a 1/100 what are the chances that there child will be affected by the AR disease?

Answer 4

(1/50) * (1/100) = 1/5,000

(1/5000) * (1/4) = 1/20,000

Question 5

Why are X-linked dominant genes never passed through the male line?

Answer 5

Male only passes y chromosome

Question 6

In an aut dominant disease if there is one affected parent what percentage of offpsring will have the disease?

Answer 6

50%

Question 7

What is Incomplete dominance?

Answer 7

Aut dom disease where the heteroztgote phenotype is different (less severe) than the homozygote (more severe)
- E.g familial hypercholesterolemia and achondroplasia

Question 8

What is an example of a disease with incomplete dominance, where in homozygote individuals it is fatal?

Answer 8

Achondroplasia
- In heterozygotes it causes dwarfism

Question 9

Why in X-linked disorders are males always affected (whether it is dominant or recessive)?

Answer 9

They only have one X chromosome

Question 10

How can a X-linked recessive disorder be identified?

Answer 10

All males with gene will be affected
- No females affected (usually)
- No male to male transmission

Question 11

How can a X-linked dominant disorder be identified?

Answer 11

All males with gene will be affected and will have it transmitted through the mother’s side
- Females will be affected
- Affected father MUST give diseased X chromosome to daughter
- NO male to male transmission, affected father will NOT pass disease to son

Question 12

What percentage of sons of heterozygous mothers with an AR allele will be affected by disease?

Answer 12

50%

Question 13

What are the 2 ways a female may develop an X-linked recessive gene?

Answer 13

• If homozygous for gene (father affected and mother a carrier)
• Skewed lionization

Question 14

What is lyonization?

Answer 14

Inactivated of X chromosome in females

Question 15

What is the lyonized X chromosome known as?

Answer 15

Barr body

Question 16

How is the X chromosome lyonized or inactivated?

Answer 16

Condensed into heterochromatin w. methylated DNA

Question 17

When does lyonization occur?

Answer 17

Early in development
- Embryo <100 cells

Question 18

What does lyonization result in?

Answer 18

Mosaicism
- Different inactive X chromosomes in different cells as it is a random process

Question 19

How can you differentiate an X-linked dominant disorder from an Aut Dom pattern?

Answer 19

No male-male transmission in X-linked disease
- Father always passes Y chromosome

Question 20

Whaty is the second most common cause of intellectual disability?

Answer 20

Fragile X syndrome

Question 21

What are the features of fragile X syndrome?

Answer 21

• Long, narrow face, large eears and jaw
• Features of autism
• More severe in males

Question 22

What organs are most affected by mitochondrial gene mutations?

Answer 22

• CNS
• Skeletal muscle
  Both heavily rely on aerobic metabolism

Question 23

A mixture of abnormal and normal genes in mitochondria is known as what?

Answer 23

Heteroplasmy

Question 24

What does the mutant gene expression levels depend on?

Answer 24

• Amount of normal vs abnormal genes
• Number of mutant mitochondria in each cell/tissue

Question 25

What is the difference beetween a homoplasmic and heteroplasmic mother?

Answer 25

Homoplasmic mothers
- All children have mutation

Heteroplasmic
- Variable

Question 26

Why may not all children display disease if their mother has a mitochondrial disease?

Answer 26

Mother may be heteroplasmic

Question 27

What are the 3 classic signs of mitochondrial myopathies?

Answer 27

• Weakness
• Confusion
• Lactic acidosis

Question 28

Wwhat is the classic sign of mitochondrial myopathy on biopsy?

Answer 28

Red ragged fibres
- compensatory proliferation of mitochondria which accumulate and appear bright red on blue background

Question 29

Multifactorial inheritance is what?

Answer 29

Genes, lifestyle and environemnt contributing toward disease

Question 30

What is polygenic inheritence?

Answer 30

inheritance of a trait governed by more than one genes