RA11 Human Genetics Inheritance Patterns Flashcards
Mendel’s Laws of Inheritance (3)
- Law of Segregation
- Law of Independent Assortment
- Law of Dominance
Law of Segregation
- During gamete formation, thw two alleles of each gene separate from each other
- Only one copy of each gene is found in each gamete
Law of Independent Assortment
- During gamete formation, different alleles for different genes sort into gametes randomly
- Maternal or paternal source of the allele is not a deciding factor as to which allele goes into which gamete
Law of dominance
- Specific traits need a specific number of allele copies to manifest
- Dominant: 1 copy
- Recessive: 2 copies
- Codominant: both alleles expressed equally in phenotype
Pedigree symbols
What inheritance pattern is this?
What characteristics does it have?
Autosomal dominant
- Only one copy of variant allele needed to show the trait
- Affected individuals are present in every generation
- Male-to-male transmission is possible (vs X-linked recessive: no male-to-male transmission)
Mendelian inheritance - monogenic trait
What inheritance pattern is this?
What characteristics does it have?
Autosomal Recessive
- Two copies of variant allele needed to show the trait
- Skips generations
Mendelian inheritance - monogenic trait
What inheritance pattern is this?
What characteristics does it have?
X-linked Recessive
- Gene carried on X chromosome
- Trait typically seen only in males
- All males that inherit the variant allele will be affected (hemizygous)
- No male-to-male transmission - only females transmit to males
Manifesting carriers
- Presence of one allele is enough to cause clinical findings for autosomal recessive conditions
- Manifestation might be similar to full condition or clinically distinct
- E.g. sickle cell trait, Gaucher disease, Nijmegen breakage syndrome
Penetrance
- The likelihood that a phenotype will be present when a specific genotype is present
- Range: 0 to 1
- Incomplete penetrance: < 1
- Complete penetrance: 1
Expressivity
- The degree to which a trait is expressed
- There can be variable expressivity across individuals with the same disease causing genotype
Genetic anticipation
- Successive generations show earlier onset and more severe disease state
- E.g. Huntington’s Disease
- Multiple mechanisms, including trinucleotide repeat expansion of microsatellites
Mosaicism
- An individual has 2 genetically distinct populations of cells
- Typically results from a mutation the occurs during embryogenesis (e.g. mutation in blastomere)
Imprinting
- Selective expression of one allele of a gene, dependent on which parent the chromosome came from
- Allele on opposite chromosome is silenced
- E.g. Angelman syndrome, Prader-Willi syndrome, Beckwith-Wiedemann syndrome
- Imprints are erased and resetablished during gamete formation
What inheritance pattern is this?
What characteristics does it have?
Mitochondrial inheritance
- Mitochondrial DNA is inherited only from females
- Affected female will pass trait to ALL offspring
- Male and female offspring have EQUAL chance of inheriting trait
- Affected male CANNOT pass on trait
Complex traits result from variation in (…) genes and are influenced by (…) and (…) factors
Complex traits result from variation in multiple genes and are influenced by behavioural and environmental factors
Mendelian causative gene
vs
complex susceptibility gene
- Casuation with disorder?
- Inheritance pattern?
- How many genes involved?
- Leads to what kind of diseases?
Mendelian causative gene
- Gene directly leads to disorder
- Recognisable inheritance patterns
- One gene per family
- Leads to less common diseases (e.g. cystic fibrosis, muscular dystrophy)
Complex susceptibility gene
- Gene confers an increased risk, but does not directly cause disorder
- No clear inheritance pattern
- Involves many genes or genes and environment
- Leads to common diseases in population (e.g. cancer, heart disease, dementia)
Phenocopy
A phenotype produced by an envrionmental effect that matches a phenotype produced by a specific genotype (i.e. a genetic mimic)
Alzheimer’s disease is characterised by the presence of what in the brain?
β-amyloid plaques and neurofibrillary tangles
How are the β-amyloid plaques in Alzheimer’s disease formed?
Abnormal cleavage of amyloid precursor protein by β-secretase (APP mutation) and γ-secretase (PSEN1/PSEN2 mutation) -> excess amyloid accumulation and aggregation -> β-amyloid plaques
What are the 4 genes associated with Alzheimer’s disease?
- PSEN1
- PSEN2
- APP
- APOE
Inheritance pattern of Alzheimer’s disease
Autosomal dominant inheritance
The (…) allele of the (…) gene is a predisposing factor to developing Alzheimer’s disease
The E4 allele of the APOE gene is a predisposing factor to developing Alzheimer’s disease
