Genetics - Mode of Inheritance Flashcards
What are the 4 modes of inheritance?
- Autosomal dominant
- Autosomal recessive
- Sex-linked
- Mitochondrial
What is autosomal dominant disorder?
Heterozygous w/ dominant allele (mutation in one copy of gene)
What is the pedigree pattern for autosomal dominant?
Vertical
What types of changes characterise autosomal dominant disorder?
- Gain-of-function
- Dominant negative effect
- Haploinsufficiency (insufficient gene for function)
What is autosomal recessive disorder?
Homozygous recessive alleles
What is the pedigree pattern for autosomal recessive?
Horizontal
What is a risk factor for autosomal recessive disorder?
Consanguineous marriages
What characterises autosomal recessive disorders?
Loss of gene function
What are the types of different sex-linked disorders?
- X-linked
- X-linked Dominant
- Y-linked
What is X-linked disorder?
Recessive mutation on X chromosome - effectively dominant in male
How does X-linked disorder affect female?
When there are mutations on both X chromosomes
Why do some female carriers of X-linked disorder show symptoms?
During development, one gene is silenced which could be the normal gene
So defective gene is expressed
What is the percentage of a children being affected if there was a carrier mother and normal father in X-linked disorder?
Half of sisters would be carrier
Half of brother would have disorder
What is the percentage of children being affected if there was an affected father and normal mother in X-linked disorder?
All daughters would be carriers and all brothers would be normal
What is the characteristic of X-linked disorder?
Parents and children of affected people would most likely be unaffected
What is X-linked dominant disorder?
Similar to autosomal dominant but only daughters (no son) of an affected father would be affected
What are the characteristics of X-linked dominant disorder?
- Gain-of-function
- Dominant negative effect
Why is the effect milder and more variable in female (dominant disorders)?
Due to X-inactivation, some tissues have normal X active
What is Y-linked disorder?
Mutation of Y chromosome (Very few due to limited no. fof genes encoded on it)
What is the pattern of Y-linked disorder?
Vertical pedigree pattern - only males affected (ALL sons of an affected father are affected)
What are mitochondrially inherited disorders?
Mutations on nuclear genes that encodes majority of mitochondrial protein and also in mitochondrial DNA
What characterise mitochondrially inherited disorders?
All mitochondrial genes are inherited from mother (maternally inherited)
- so VERTICAL pedigree diagram
What are the 2 factors that drive variability of mitochondrial inherited disorders?
- Heteroplasmy
- Variability in no. of mitochondria affected per cell
Only when threshold is reached, will it show disease
What is heteroplasmy?
Mitochondria has multiple copies of genome (only some will contain mutation / bacterial origin means when it replicates by binary fission - it loses/gains mutated genes)
What affects the number of mutated mitochondria in cell?
- Change when cell divide
- Develop with age, accumulation of mutant mitochondria
Why is mitochondrial inherited disease so hard to diagnose?
Motor and nerve function are commonly affected, therefore wrong diagnosis
