Human variation in health and disease Flashcards
What is human genetic variation?
- Variation in sequence or structure of the the human genome
- Inter-individual, inter-population
What are the mechanisms of human genetic variation?
- Meiotic recombination
- DNA replication and repair
- Random genetic drift, natural selection, migration
What is structural variation?
- Copy number (deletions and duplications)
- Positional (insertions, translocations)
- Orientation (inversions)
What is sequence level variation?
- Single base substitutions
- Small deletions/duplications
- Repetitive sequence
What is cytogenetics
Studies the structure, properties and behaviour of chromosomes
What is molecular genetics?
Studies structure and function of genes at a molecular level
What is phenotype?
A set of observable characteristics of an individual resulting from the interaction of it’s genotype with the environment
What is the spectrum of consequence of variation on phenotype?
- No change
- Alternative phenotypes of no medical consequence
- Disease susceptibility
- Pathogenic
What is continuous variation?
- No limit on the value that can occur within a population
- Line graph
- E.g. height, weight, heart rate, finger length
What is discontinuous variation?
- Distinct groups for organisms to belong to
- Bar graph
- E.g. tongue rolling, finger prints, eye colour, blood groups, detached earlobes
What is epigenetics?
- Heritable changes in gene expression that do not involve changes to the underlying DNA sequences
- Changes in phenotype without change in genotype
- Influenced by age, environment/lifestyle, disease state
Define locus
Location of a gene/marker on a chromosome
Define allee
One variation form of a marker at a particular locus
Describe polymorphism
- Variations in DNA sequence that are >1% in a population
- Ancient and common
- Weak or no effect
Describe mutation
- Variants in DNA sequences <1% ina population
- Recent and rare
Describe monogenic disease
- Changes in one gene sufficient for a disease
- One gene -> one or more disorders
- Multiple genes -> individually cause same single disorder
- Comparatively rare
- E.g. Fragile X and CF
Describe polygenic disease
- Multiple genes contribute to phenotype, each exerting as mall effect
- E.g. eye colour
Germline
- Cell line from which gametes are derived
- Mutation will be in all tissues
Somatic
- Cells arise from the germline
- Mutation will only be in affected tissues
What are the types of mutations?
- Mode of inheritance
- Genomic location
- Molecular change
- Functional effect
What are sequence level mutations?
- Missense
- Nonsense and frame-shifting
- Splicing
- Others that affect gene expression
- Dynamic mutations
Describe copy number mutations
- Single gene, continuous gene and multiple gen syndromes
- Molecular mechanisms: gene dosage, gene interruption, gene fusion, position effects, unmasking of recessive alleles
