Patterns of inheritance Flashcards
Have a look at pedigree drawings and the signs
On first page of notes
What is autosomal dominance?
- Multiple generations affected
- Both sexes affected
- Male to female & female to male transmission
- Most will have an affected parent
What are the charactertistics of autosomal dominance? (4 marks)
- Most individuals have an affected parent (not everybody due to cases of new mutations or incomplete penetrance).
- Males and females are equally likely to inherit the allele and be affected.
- Risk for each child of an affected parent is ½.
- If an affected individual’s siblings/children are not affected, and they do not carry the mutation they cannot pass it on to their own offspring.
Define Penetrance
Percentage of individuals who carry the mutation AND develop symptoms of the disorder
– many dominant disorders show age-dependant penetrance
– some people can have reduce penetrance
– e.g Huntington’s disease
What are obligate carriers?
Obligate carriers are people who are heterozygous but have not got the disease, they can pass this mutation on.
How do we calculate Penetrance?
Number of individuals with disease/ number of people with genotype of disease x 100
Explain the terms: Variable Expressivity, New mutation rate, Somatic mosaicism, Germ-line mosaicism (gonadal mosaicism and Anticipation which are all features of autosomal dominance
- Variable Expressivity: variation in severity/symptoms of disorder between individuals with same mutn . Can occur within the same family
- New mutation rate: de novo mutation rate varies considerably between AD conditions
• Somatic mosaicism: new mutn arising at early stage in embryogenesis
o Present in only some tissues/cells
• Germ-line mosaicism (gonadal mosaicism): new mutn arises during oogenesis or spermatogenesis
o mutn present in variable proportion of gametes; can be transmitted to offspring
• Anticipation: worsening of disease severity in successive generations
o characteristically occurs in triplet repeat disorders
What are the features of Autosomal Recessive Inheritance
• Manifest in HOMOZYGOUS/ COMPOUND HETEROZYGOUS form • Carriers (heterozygote) not affected • Both sexes affected • Male to female and female to male transmission • Usually one generation affected • May be consanguinity e.g. cousin marriages Refer to image as well
How can cystic fibrosis cause a compound heterozygous?
How can cystic fibrosis cause compound homozygous?
Hetrozygous:
– 2 mutns in same gene
– Mutns are different
• Cystic fibrosis
– ∆F508
– G542X
Homozygote: – 2 mutns in same gene – Identical mutns • Cystic fibrosis – ∆F508 – ∆F508 • May suggest consanguinity
What are the features of Autosomal Recessive Inheritance? (4)
- Trait often found in clusters of siblings but not in parents & 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.
What is X linked inheritance?
Women have two X chromosomes
Two copies of X-linked genes
Can be homozygous or heterozygous
Men have one X and a Y
Only a single copy of X-linked genes
Hemizygous
How can X linked heriatnce be recessive or dominant?
• Recessive Women are carriers + unaffected No male to male transmission • Dominant Women are affected Males more severely affected/lethal
Give 3 aspects of X-linked Recessive Inheritance
- X-linked genes never passed from father to son.
- All daughters of affected males are obligate carriers.
- Children of carrier females have a 50% chance of inheriting mutant allele.
What is Skewed X-inactivation and Manifesting carriers
- Skewed X-inactivation: generally random but ~10% of women have uneven or skewed X-inactivation.
- Manifesting carriers: some women have some symptoms in X-linked recessive conditions e.g. cardiomyopathy in DMD.
What is Y linked inheritance
Always and only passed from fathers to sons
