2 - Human Variation in Health & Disease

Question 1

Human genetic variation

Answer 1

• Variation in structure or sequence of the human genome
• Can be both within and among populations (inter-individual, inter-population)

Question 2

What mechanisms contribute to genetic variation

Answer 2

• Meiotic recombination
• Mutagens (Ionising radiation, UV, chemicals)
• DNA replication and repair
• Population effects (random genetic drift, selection, migration)
• Retrotransposition

Question 3

Types of variation

Answer 3

Structural (>1000bp) or sequence level (<1000bp)

Question 4

Structural variation mutations

Answer 4

Deletions, duplications, insertions, translocations, inversions

Question 5

Sequence level variation

Answer 5

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

Question 6

cytogenetics

Answer 6

Structure, properties and behaviour of chromosomes

Question 7

Retrotransposition

Answer 7

• Elements able to amplify themselves throughout the genome.
• Copy themselves to RNA and then back into DNA that integrates back into the genome

Question 8

Human reference genome

Answer 8

• Created by sampling lots of individuals of varying genetic make-up.
• Not necessarily appropriate when comparing large range of ethnicities
• Any individual will have 10s of thousands of
  structural and sequence variants when compared to
  the reference genome (any may contribute to phenotype)

Question 9

Phenotype

Answer 9

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

Question 10

Spectrum of consequences of genetic variation

Answer 10

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

Question 11

Continuous variation

Answer 11

No limit on the value that can occur within a population (e.g. height, weight, heart rate)

Question 12

Discontinuous variation

Answer 12

Has distinct groups for organisms to belong to (e.g. tongue rolling, blood groups, eye colour)

Question 13

Examples of genetic diseases

Answer 13

• Down syndrome
• Cystic fibrosis
• Sickle cell disease

Question 14

Examples of complex diseases

Answer 14

• Diabetes (type 2)
• Alzheimer disease
• Cardiovascular disease
• Obesity

Question 15

Examples of environmental diseases

Answer 15

• Measles
• Hepatitis
• Influenza

Question 16

Epigenetics

Answer 16

Heritable changes to gene expression that do not involve changes to underlying DNA sequence (change in phenotype without change in genotype)

Question 17

Mechanisms that lead to epigenetic changes

Answer 17

• DNA methylation
• Histone modification
• Non coding RNA

Question 18

Central dogma of molecular biology

Answer 18

DNA –> RNA –> Protein

Question 19

Locus

Answer 19

Location of a gene on the chromosome

Question 20

Allele

Answer 20

One variant form of a gene at a particular locus

Question 21

Polymorphism

Answer 21

• Variations in DNA sequence (e.g. deletions, insertions
• Weak or no effect
• Common in normal population

Question 22

Mutation

Answer 22

• Variants in DNA sequences
• Can produce a loss or gain of function

Question 23

Monogenic disease

Answer 23

Changes in one gene sufficient for disease

Question 24

Polygenic

Answer 24

Multiple genes contribute to phenotype, each exerting a small effect (e.g. eye colour)

Question 25

Germ line cells

Answer 25

• Germ line is the cell line from which gametes are derived
• Any tissue from that patient can be sampled for genetic testing
• Can be inherited

Question 26

Somatic cells

Answer 26

• Somatic cells arise from germline, but are not part of it
• Mutation will only be in affected tissues, not all tissues.
• Not inherited