6. INHERITANCE PATTERNS Flashcards
What are the four modes of Mendelian inheritance?
- Autosomal Dominant
- Autosomal Recessive
- X-linked
- Y-linked
*What is autosomal dominant inheritance?
- Autosomal dominant disorders only require one copy of the gene so they manifest in the HETEROZYGOUS FORM
- Individuals with one copy will therefore be affected
- 50% chance that offspring will be affected if one parent is affected
- Both sexes can be affected
- Most affected individuals will have a parent who is affected but not always, could be due to new mutations arising or penetrance
What are 6 features of autosomal dominant inheritance?
- Penetrance
- Variable Expressivity
- De novo mutation rate
- Somatic Mosaicism
- Germ-line Mosaicism
- Anticipation
What is penetrance?
- Penetrance refers to the percentage of individuals who have the mutation go on to develop symptoms
- Reduced penetrance = not everyone with genotype develop symptoms
- 100% penetrance = almost always develop symptoms
- Age-dependent penetrance is characteristic of autosomal dominant disorders
What is variable expressivity?
- Variable expressivity refers to the symptoms of a disorder differing between individuals
What is mosaicism & what are the two types of mosaicism?
- Mosaicism is when the genetic make up of two or more cells differ in an individual as a result of error in mitosis
1. Somatic mosaicism
2. Germ-line mosaicism
What is somatic mosaicism & germ-line mosaicism?
- Somatic mosaicism occurs during the early stages of embryogenesis. Only the daughter cells that arise from the mutated cell will be affected
- Germ-line mosaicism occurs during oogenesis/spermatogenesis. A variable proportion of gametes will be affected, the mutations can be passed on to offspring but this due to random chance
What is autosomal recessive inheritance?
- Autosomal recessive disorders require two copies of the gene in order to be affected
- It can manifest as HOMOZYGOUS or COMPOUND HETEROZYGOUS
- Individuals with only one copy of the gene are considered to be carriers
- Autosomal recessive disorders only tend to affect one generation & can be characteristic of consanguinity (cousin marriages)
What’s the difference between compound heterozygote & homozygote (autosomal recessive inheritance)?
- Compound heterozygote - inherit two different mutations of the same gene. Two mutations of the same gene that aren’t identical
- Homozygote = two mutations of the same gene that are identical. May be characteristic of consanguinity
What are the genotypes for X-linked disorders for men & women?
- Women have two X chromosomes so can be HOMOZYGOUS or HETEROZYGOUS
- Men only have one X chromosome so they can only be HEMIZYGOUS
What are the characteristics of recessive X-linked inheritance?
- Women are carriers & are unaffected, due to X-inactivation
- There is no male to male transmission as men cannot pass on an X chromosome to their sons
What are the characteristics of dominant X-linked inheritance?
- Women can be affected as they only need one copy, so X inactivation an still mean an X with dominant gene is active
- Men are more severely affected
Why does X inactivation lead to manifesting carriers?
- In women, one of the X chromosomes will be inactivated in some cells whilst others will have both active. Most of the time the X chromosome with the mutation will be inactivated
- HOWEVER, some women will have SKEWED X INACTIVATION where the X chromosome without the mutation is inactivated meaning that the X chromosome with the mutation can is active.
- This can lead to manifesting carriers
What are the three main types of mutation?
- Substitution
- Deletion
- Insertion
*What is a silent mutation?
- A silent/synonymous mutation leads to an base change without changing the AA. This is because more than one codon codes for an AA.
