G2 +3- Single gene disorders Flashcards
what are the classifications of genetic disease?
• Chromosomal abnormalities • Single gene disorders : - Autosomal dominant -Autosomal recessive -X-linked (recessive and dominant) -Mitochondrial • Multifactorial traits (polygenic)
What are autosomal dominant traits?
- affected heterozygotes
- 50% risk for offspring of affected individuals
- males and females equally affected
- variable expression
- variable penetrance
what is variable expression?
• Many genetic conditions have a range of clinical features
• Many affected people:
– only have some features
OR
– show some features to a varying degree
what is variable penetrance?
The proportion of people with a genotype who show the associated phenotype
what is age dependent penetrance?
The proportion of people with the predisposing genotype that show the associated phenotype increases with age
what is type 1 osteogenesis imperfecta?
Mutation reduces rate of production of one of collagen subunits
what are characteristics of osteogenesis imperfecta?
- Brittle bones
- Frequent fractures
- Osteopenia (undermineralised bones)
- Blue sclerae
- Deafness
- Abnormal dentition in some forms
what is Type II osteogenesis imperfecta?
- Mutation results in production of structurally abnormal collagen
- New mutations because affected pregnancies do not survive
- Low recurrence risk
what condition is cystic fibrosis ?
autosomal recessive condition
what are characteristics of autosomal recessive condition- cystic fibrosis?
- 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
what is the risk of CF in children of carrier couple?
1/4
Describe genetic testing for cystic fibrosis.
• 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
Describe cascade screening for CF carriers.
relatives of affected children
Describe population screening for CF carriers.
• pre-pregnancy
• early in pregnancy:
-couple screening
- mother first and father if mother is a carrier
what are high risk populations in haemoglobinopathies (thalassaemia /sickle cell disease)?
- Mediterranean
- Africa
- Indian subcontinent
What are autosomal recessive traits?
- 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
Describe Duchenne muscular dystrophy.
- 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
Describe X-linked recessive traits?
- 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
Who is affected most by X-linked dominant trait?
males more severely affected than females
Describe X-linked dominant traits.
- 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
