RA11 Human Genetics Inheritance Patterns

Question 1

Mendel’s Laws of Inheritance (3)

Answer 1

1. Law of Segregation
2. Law of Independent Assortment
3. Law of Dominance

Question 2

Law of Segregation

Answer 2

• During gamete formation, thw two alleles of each gene separate from each other
• Only one copy of each gene is found in each gamete

Question 3

Law of Independent Assortment

Answer 3

• 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

Question 4

Law of dominance

Answer 4

• Specific traits need a specific number of allele copies to manifest
• Dominant: 1 copy
• Recessive: 2 copies
• Codominant: both alleles expressed equally in phenotype

Question 5

Pedigree symbols

Question 6

What inheritance pattern is this?
What characteristics does it have?

Answer 6

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

Question 7

What inheritance pattern is this?
What characteristics does it have?

Answer 7

Autosomal Recessive
- Two copies of variant allele needed to show the trait
- Skips generations

Mendelian inheritance - monogenic trait

Question 8

What inheritance pattern is this?
What characteristics does it have?

Answer 8

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

Question 9

Manifesting carriers

Answer 9

• 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

Question 10

Penetrance

Answer 10

• The likelihood that a phenotype will be present when a specific genotype is present
• Range: 0 to 1
• Incomplete penetrance: < 1
• Complete penetrance: 1

Question 11

Expressivity

Answer 11

• The degree to which a trait is expressed
• There can be variable expressivity across individuals with the same disease causing genotype

Question 12

Genetic anticipation

Answer 12

• Successive generations show earlier onset and more severe disease state
• E.g. Huntington’s Disease
• Multiple mechanisms, including trinucleotide repeat expansion of microsatellites

Question 13

Mosaicism

Answer 13

• An individual has 2 genetically distinct populations of cells
• Typically results from a mutation the occurs during embryogenesis (e.g. mutation in blastomere)

Question 14

Imprinting

Answer 14

• 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

Question 15

What inheritance pattern is this?
What characteristics does it have?

Answer 15

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

Question 16

Complex traits result from variation in (…) genes and are influenced by (…) and (…) factors

Answer 16

Complex traits result from variation in multiple genes and are influenced by behavioural and environmental factors

Question 17

Mendelian causative gene
vs
complex susceptibility gene
- Casuation with disorder?
- Inheritance pattern?
- How many genes involved?
- Leads to what kind of diseases?

Answer 17

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)

Question 18

Phenocopy

Answer 18

A phenotype produced by an envrionmental effect that matches a phenotype produced by a specific genotype (i.e. a genetic mimic)

Question 19

Alzheimer’s disease is characterised by the presence of what in the brain?

Answer 19

β-amyloid plaques and neurofibrillary tangles

Question 20

How are the β-amyloid plaques in Alzheimer’s disease formed?

Answer 20

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

Question 21

What are the 4 genes associated with Alzheimer’s disease?

Answer 21

• PSEN1
• PSEN2
• APP
• APOE

Question 22

Inheritance pattern of Alzheimer’s disease

Answer 22

Autosomal dominant inheritance

Question 23

The (…) allele of the (…) gene is a predisposing factor to developing Alzheimer’s disease

Answer 23

The E4 allele of the APOE gene is a predisposing factor to developing Alzheimer’s disease