Family Histories + Probabilities

Question 1

Name the main features of autosomal dominant inheritance

Answer 1

• multiple generations
• men + women equally affected (problematic gene on non-sex chromosome)
• male -> male transmission
• incomplete penetrance
• variable expression
• can be new mutation in family

Question 2

What is the offspring inheritance risk in autosomal dominant inheritance?

Answer 2

50% offspring risk
BUT risk of being affected dependent on penetrance:
risk = 1/2 x penetrance

Question 3

What is incomplete penetrance?

Answer 3

Can have mutation and never develop signs of disease

Question 4

Name some autosomal dominant conditions

Answer 4

• Huntington’s
• Marfan syndrome
• Familial hypercholesterolaemia
• Spinocerebellar ataxia
• Familial adenomatous polyposis
• HBOC
• Myotonic dystrophy
• Long QT syndrome

Question 5

Name the main features of autosomal recessive inheritance

Answer 5

• only 1 generation affected
• parents = asymptomatic carriers
• childhood onset
• common in consanguineous families

Question 6

Name some autosomal recessive conditions

Answer 6

• Cystic fibrosis
• Phenylketonuria
• B-Thalassemia
• Sickle cell anaemia
• Tay Sachs disease
• Spinal muscular trophy

Question 7

What is the offspring risk in autosomal recessive inheritance?

Answer 7

• 25% recurrence risk after already having affected child
• 2 unaffected individuals can have child with disorder =
  1/4 x mums carrier risk x dads carrier risk
• probability healthy sibling of someone with disorder is carrier = ALWAYS 2/3

Question 8

Name the main features of X-linked recessive inheritance

Answer 8

• only men affected
• females = asymptomatic carriers -> 50% sons affected, 50% daughters carriers
• all daughters of affected men = carriers + all sons = affected
• can be new mutation

Question 9

What is the offspring risk in X-linked recessive inheritance?

Answer 9

Overall 25% children affected

Question 10

Name some X-linked recessive conditions

Answer 10

• Duchenne muscular dystrophy
• Haemophilia A
• Red-green colour blindness

Question 11

What is germline mosaicism?

Answer 11

Some eggs carry mutation but are not in blood

Question 12

What is the Hardy Weinberg equation based on

Answer 12

Allele frequencies in population will remain constant 1 generation to next provided:

• large population size
• no mutation
• no immigration/emigration
• random mating
• random reproductive success

Question 13

What is the Hardy Weinberg equation?

Answer 13

p^2 + 2pq + q^2 = 1
p + q = 1

p = frequency of A allele 
q = frequency of a allele

Question 14

What is q^2 in the HWE?

Answer 14

incidence of disease

Question 15

Where is the carrier frequency derived from?

Answer 15

2pq