Inheritance Patterns

Question 1

Describe the occurrence of autosomal dominant inheritance

Answer 1

• manifest in heterzygous genotypes
• homozygous dominant may terminate foetus therefore not observed usually
• male to female transfer (not sex-linked)
• 50% chance of affecting offspring
• depends on de novo mutations as those with genotype may not survive to produce offspring (severely reduced survival/fitness)

Question 2

Describe the occurrence of autosomal dominant recessive

Answer 2

requires homozygous recessive genotype
- heterozygous = carriers (standard heterozygotes)
- not sex-linked
- increased recessive disorders with cosanguinity/ in-family marriages
- traits presented in siblings not parent/offspring
- 1:2:1 inheritance ratio, 1in4 for siblings, 2/3 probability of non-affected siblings becoming carriers
- all offspring are defined as obligate carriers

Question 3

How do X-linked inheritance patterns occur?

Answer 3

• 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.
• Skewed X-inactivation: generally random but ~10% of females have uneven or skewed X-inactivation.
• Manifesting carriers: some females have some symptoms in X-linked recessive
  conditions e.g. cardiomyopathy in DMD.

Question 4

How does Y-linked inheritance occur?

Answer 4

palandric disorders
eg: hairy ear syndrome
exclusively transmitted to father => son

Question 5

Define the following genetic terms:
- Incomplete Penetrance

Answer 5

Incomplete Penetrance
to possess a mutation without inheriting the disease

Question 6

Define the following genetic terms:
-Variable Expressivity

Answer 6

Variable Expressivity
individuals with the same mutation presenting with various degrees in severity/symptoms of disease

Question 7

Define ‘de novo mutation’

Answer 7

idea of affected patients not having an affected parent. The severity of a disease preventing fitness/survival may result in non carrying parents to have affected offspring
(eg: severe autosomal dominant diseases)

Question 8

Define mosaicism

Answer 8

When mutation is only present in proportion of cells
(could be somatic of in gametes)

Question 9

Define anticipation in genetic terms

Answer 9

Successive generations presenting with worsening/ more severe symptoms of inherited disease
(eg: expansive disease, Huntingtons)

Question 10

Define the following variants:
synonymous
missense
nonsense
insertion
deletion

Answer 10

synonymous: ‘silent mutations’ base change without affecting amino acid change (degenerate feature of DNA) common in 3rd base

missense: non-synonymous results in change of amino acid sequence. Not all missense is pathogenic, but difficult to predict. Affects functional role in protein. How well is it conserved among different species

nonsense: non-synonymous premature stop codons. options include; decay of non-functional protein, truncated protein. not all are pathogenic.

insertion : indels, could be single base of multiple base, if insertion is not multiple of 3 causes frame shift, causing every codon afterward to change mostly pathogenic

deletion: indels. deletion of 3 at the end is less likely to be pathogenic. Frame shifts also apply here.