Basics of Clinical Genetics Flashcards
Give an example of a purely genetic and environmental disease
- G= Duchenne Muscular Dystrophy
- E = Scurvy
What makes human diseases rare or common?
- Common= Genetics complex, multifactorial, low recurrence rate
- Rare= unifactorial, high recurrence rate, genetics simple
How are genetic disorders classified?
- Multifactorial/Complex
- Single gene
- Chromosomal
- Mitochondrial
- Somatic mutations
How can genetic defects be inherited?
- Autosomal dominant
- Autosomal recessive
- X-linked
- Mitochondrial
Describe Autosomal Dominant inheritance
- Runs from one generation to the next
- Males & females equally affected
- Offspring of affected have 1/2 chance of inheriting mutation
- Structural proteins, receptors, transcription factors
- Marfan Syndrome, Huntingtons, Myotonic Dystrophy
- Can be chromosome deletion
Define Penetrance
Frequency with which a specific genotype is expressed by those individuals that possess it(%)
(Huntingtons=100% BRCA1 mutation= incomplete penetrance)
Define expressivity
Variation in expression- the extent to which a heritable trait manifests in an individual
(Marfan Syndrome= aortic dilatation, lens dislocation, BRCA1 mutation= breast/ovarian cancer)
Define anticipation
Symptoms of a genetic disorder become apparent at an earlier age as it is passed from one generation to the next. Usually with increasing severity- Huntingtons.
Define New dominant/De Novo mutation
New mutation that has occurred during gametogenesis/ early embryonic development with neither parents affected but individual can pass to their children
Describe Autosomal Recessive inheritance
- Disease seen in one generation
- Offspring of affected low risk 25% unless consanguineous relationship
- Affects males & females equally
- Gene mutations not chromosomes
- Cystic Fibrosis, Sickle Cell Anaemia, Haemachromatosis, metabolic disorders
Describe X-linked inheritance
- Males affected
- Females can be mildly or fully affected
- Males more severe than females
- No male to male transmission
- Gene mutations & chromosome deletions/duplications
- Haemophilia, Fragile X Syndrome, Colour blindness, Duchenne Muscular Dystrophy
What 2 main factors influence expression of a phenotype?
- X inactivation
- X-linked dominant vs X-linked recessive inheritance
What is X-inactivation?
- Lyonisation
- Occurs in early embryogenesis
- Process of random inactivation/silencing of one X chromosome in cells with more than one X chromosome
- Compensates for the presence of double X gene dose
- Remains inactive all cells life and its descendants
- Most genes switched off but some left on
What is skewed X-inactivation?
Switching off of ‘normal’ X chromosome
What are X-linked dominant diseases?
- Rett Syndrome
- Fragile X Syndrome
