Genetic variation

Question 1

What is Ellis-Van Creveld Syndrome?

Answer 1

Autosomal recessive condition

Question 2

What is the typical different between 2 genomes?

Answer 2

3 million SNP (0.1% of total 3.2 billion base pairs)

Question 3

What is the human genome project?

Answer 3

1990-2003

-Complete mapping and understanding of all genes of human beings.

Question 4

What are introns?

Answer 4

DNA that does not code for proteins (removed by RNA splicing)
Exons (coding) = 1.5% of genome

Question 5

How are exons bonded to eachother?

Answer 5

covalently

Question 6

what % of the genome are genes (exons/ introns)

Answer 6

25%

Question 7

What are the characteristics of hereditary variants?

Answer 7

• Inherited from a parent
• Present throughout life / in every cell
• Present in egg/sperm cells

Question 8

What are characteristics of acquired variants?

Answer 8

• Occur at some time during a person’s life
• Only in certain cells
• Not passed down

Question 9

What are microsatellites?

Answer 9

• Repeats of short segments
• 1-10 Nucleotides
• Prone to mutations due to slippage
• mutation rates at micros > SNP

Question 10

What are structural variations?

Answer 10

• Large scale genomic variation >1KB
• Chromosomal abnormalities e.g. inversion
• Aneuploidy

Question 11

Define polymorphism

Answer 11

• DNA sequence variation common in the population (>1%)

- Two or more acceptable alternatives

Question 12

Explain single nucleotide polymorphisms

Answer 12

simple type of mutations: 3 types: substitution, deletion &amp, insertion (point mutation)

Question 13

When can SNP be detected?

Answer 13

• Phenotypic level
• Restriction fragment level
• Sequence level of DNA

Question 14

What are tandem repeats?

Answer 14

-Very unstable
-repeating sequence that lies next to each other
-

Question 15

How do repeat polymorphisms occur?

Answer 15

Addition/deletion of entire repeat units

Question 16

What is the difference between microsatelittes & minisatellites?

Answer 16

Micro: 1-10 nucleotides
Mini: >10 nucleotides

Question 17

Explain strand-slippage replication

Answer 17

Template & nascent strands are mismatched - this causes a loop to form but the DNA is able to bind to a later repeat causing a mutation.

• Template = contraction
• Nascent = expansion

Question 18

How does huntington’s disease occur?

Answer 18

• Micro-satellite instability
• Repeat of CAG codon
• Excess glutamine
• Progressive disease
• Severity depends on repeat count

Question 19

Explain copy number variation

Answer 19

chromosomal deletions/ duplications which involve large stretches of DNA
Can result in advantages (AMY1) or disease (psychiatric disorders)

Question 20

What is the relationship between AMY1 & evolution?

Answer 20

-AMY1 is involved in Starch hydrolysis (salivary amylase)
-Copy number = more amylase protein (more efficient)
Overtime there has been an increase in this amount as a human adaptation to agricultural lifestyle

Question 21

What is PTPN6 responsible for?

Answer 21

• early onset emphysema due to variant: ala455Thr

- genetic variants with larger effect sizes more likely to be found in familes

Question 22

Explain Thalassemia

Answer 22

Produce little / no haemoglobin
-2 types (alpha: HBA1/2 /beta: HBB)
Minor: 1 copy of HBB or 1 copy of HBA1/2 + second copies of these w/o genetic changes
- Mild/ no symptoms

Major: variant in both copies

• No fully functioning genes
• Symptoms

Question 23

Explain sickle cell anaemia

Answer 23

• Abnormal red blood cells
• Do not last (anaemia)
• Caused by mutation in HBB gene
• Needs 2 copies
• Abnormal gene in chromosome 11