Human variation in health and disease

Question 1

What is human genetic variation?

Answer 1

• Variation in sequence or structure of the the human genome

- Inter-individual, inter-population

Question 2

What are the mechanisms of human genetic variation?

Answer 2

• Meiotic recombination
• DNA replication and repair
• Random genetic drift, natural selection, migration

Question 3

What is structural variation?

Answer 3

• Copy number (deletions and duplications)
• Positional (insertions, translocations)
• Orientation (inversions)

Question 4

What is sequence level variation?

Answer 4

• Single base substitutions
• Small deletions/duplications
• Repetitive sequence

Question 5

What is cytogenetics

Answer 5

Studies the structure, properties and behaviour of chromosomes

Question 6

What is molecular genetics?

Answer 6

Studies structure and function of genes at a molecular level

Question 7

What is phenotype?

Answer 7

A set of observable characteristics of an individual resulting from the interaction of it’s genotype with the environment

Question 8

What is the spectrum of consequence of variation on phenotype?

Answer 8

• No change
• Alternative phenotypes of no medical consequence
• Disease susceptibility
• Pathogenic

Question 9

What is continuous variation?

Answer 9

• No limit on the value that can occur within a population
• Line graph
• E.g. height, weight, heart rate, finger length

Question 10

What is discontinuous variation?

Answer 10

• Distinct groups for organisms to belong to
• Bar graph
• E.g. tongue rolling, finger prints, eye colour, blood groups, detached earlobes

Question 11

What is epigenetics?

Answer 11

• 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

Question 12

Define locus

Answer 12

Location of a gene/marker on a chromosome

Question 13

Define allee

Answer 13

One variation form of a marker at a particular locus

Question 14

Describe polymorphism

Answer 14

• Variations in DNA sequence that are >1% in a population
• Ancient and common
• Weak or no effect

Question 15

Describe mutation

Answer 15

• Variants in DNA sequences <1% ina population

- Recent and rare

Question 16

Describe monogenic disease

Answer 16

• 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

Question 17

Describe polygenic disease

Answer 17

• Multiple genes contribute to phenotype, each exerting as mall effect
• E.g. eye colour

Question 18

Germline

Answer 18

• Cell line from which gametes are derived

- Mutation will be in all tissues

Question 19

Somatic

Answer 19

• Cells arise from the germline

- Mutation will only be in affected tissues

Question 20

What are the types of mutations?

Answer 20

• Mode of inheritance
• Genomic location
• Molecular change
• Functional effect

Question 21

What are sequence level mutations?

Answer 21

• Missense
• Nonsense and frame-shifting
• Splicing
• Others that affect gene expression
• Dynamic mutations

Question 22

Describe copy number mutations

Answer 22

• Single gene, continuous gene and multiple gen syndromes

- Molecular mechanisms: gene dosage, gene interruption, gene fusion, position effects, unmasking of recessive alleles