G2 +3- Single gene disorders

Question 1

what are the classifications of genetic disease?

Answer 1

• Chromosomal abnormalities
• Single gene disorders :
- Autosomal dominant
-Autosomal recessive
-X-linked (recessive and dominant) 
-Mitochondrial
•  Multifactorial traits (polygenic)

Question 2

What are autosomal dominant traits?

Answer 2

• affected heterozygotes
• 50% risk for offspring of affected individuals
• males and females equally affected
• variable expression
• variable penetrance

Question 3

what is variable expression?

Answer 3

• Many genetic conditions have a range of clinical features
• Many affected people:
– only have some features
OR
– show some features to a varying degree

Question 4

what is variable penetrance?

Answer 4

The proportion of people with a genotype who show the associated phenotype

Question 5

what is age dependent penetrance?

Answer 5

The proportion of people with the predisposing genotype that show the associated phenotype increases with age

Question 6

what is type 1 osteogenesis imperfecta?

Answer 6

Mutation reduces rate of production of one of collagen subunits

Question 7

what are characteristics of osteogenesis imperfecta?

Answer 7

• Brittle bones
• Frequent fractures
• Osteopenia (undermineralised bones)
• Blue sclerae
• Deafness
• Abnormal dentition in some forms

Question 8

what is Type II osteogenesis imperfecta?

Answer 8

• Mutation results in production of structurally abnormal collagen
• New mutations because affected pregnancies do not survive
• Low recurrence risk

Question 9

what condition is cystic fibrosis ?

Answer 9

autosomal recessive condition

Question 10

what are characteristics of autosomal recessive condition- cystic fibrosis?

Answer 10

• Chronic obstructive lung disease (thick mucus)
• Pancreatic insufficiency (viscous pancreatic juices)
• Meconium ileus (bowel obstructed by thick viscous contents)
• High sweat electrolytes (Na and Cl)
• Infertility in males
• Life expectancy reduced. Heart and lung transplant often needed in later life

Question 11

what is the risk of CF in children of carrier couple?

Answer 11

1/4

Question 12

Describe genetic testing for cystic fibrosis.

Answer 12

• over 500 different mutations described in CFTR gene
• p.Phe508del mutation accounts for 70-80% of CF mutation in UK population
• ~ 85% of CF carriers can be detected by testing
for 30 of the most common mutations found in the UK population

Question 13

Describe cascade screening for CF carriers.

Answer 13

relatives of affected children

Question 14

Describe population screening for CF carriers.

Answer 14

• pre-pregnancy
• early in pregnancy:
-couple screening
- mother first and father if mother is a carrier

Question 15

what are high risk populations in haemoglobinopathies (thalassaemia /sickle cell disease)?

Answer 15

• Mediterranean
• Africa
• Indian subcontinent

Question 16

What are autosomal recessive traits?

Answer 16

• homozygotes affected
• heterozygous carriers usually asymptomatic
• 25% recurrence risk for sibling of affected individuals
• much lower recurrence risk for other relatives
• high risk populations
• consanguinity

Question 17

Describe Duchenne muscular dystrophy.

Answer 17

• X-linked recessive
• Incidence in males: 1/3000
• Delay in motor development
• Onset of weakness in pelvic and shoulder girdles
• Wheelchair bound by 10-12 years
• Death from involvement of respiratory and cardiac muscles

Question 18

Describe X-linked recessive traits?

Answer 18

• male hemizygotes affected
• female heterozygotes usually unaffected
• 50% risk for sons of carrier females
• 50% risk that daughters of carrier females will be carriers
• all daughters of affected males are carriers
• no male to male transmission

Question 19

Who is affected most by X-linked dominant trait?

Answer 19

males more severely affected than females

Question 20

Describe X-linked dominant traits.

Answer 20

• hemizygous males and heterozygous females affected
• more severe in males
• X-linked dominant traits lethal in males
• often “patchy” in affected females (random X inactivation)
• 50% risk for sons of carrier females
• 50% risk for daughters of carrier females
• all daughters of affected males are affected
• no male to male transmission