Genetic Variation

Question 1

What are Mutations?

Answer 1

hereditable change in the base sequence of genes

Question 2

What are Genetic Variations?

Answer 2

Arise from Mutations that are positively selected described as DNA polymorphism

Question 3

What is DNA polymorphism?

Answer 3

Any difference in Nucleotide sequence

Question 4

What are the 5 reasons Mutations can arise?

Answer 4

1. Strand breakage - lose nucleotides
2. Base loss - broken glycosidic bond
3. Base change - guanine is oxidised
4. DNA crosslinking - UV light
5. DNA replication error - errors not corrected

Question 5

What happens when DNA repair mechanisms fail?

Answer 5

Leads to genetic damage

Question 6

What are the health consequences for DNA not being repaired?

Answer 6

1. Cancer susceptibility
2. Progeria
3. Neurological defects
4. Immunodeficiency

Question 7

Why do changes in DNA most commonly arise from?

Answer 7

Errors in DNA replication

Question 8

What is the Mutation Rate?

Answer 8

If it is too low organisms cant adapt, if it is too high information cant be retained

Question 9

What has the highest mutation rate?

Answer 9

Mitochondrial Genome

Question 10

How does Genetic Variation arise?

Answer 10

As a consequence of mutation - Recombination (crossover events in meiosis)

Question 11

What are the 3 Types of Mutations?

Answer 11

1. Point Mutations
2. Insertions/Deletions
3. Chromosomal Mutations

Question 12

What is a Point mutation?

Answer 12

• Changes to a single nucleotide (substitutions)

- Missense and nonsense mutations

Question 13

What is a Chromosomal mutation?

Answer 13

• Polyploidy - multiple sets of chr
• Aneuploidy- abnormal number, extra/missing chr
• Chromosome rearrangements - parts moved to other chr

Question 14

What is a Missense mutation?

Answer 14

A change in nucleotide sequence that results in a change to AA sequence

Question 15

What types of Missense mutations are they?

Answer 15

Point mutations
Frameshifts
Loss of function (PAH) Gain of function (Achondroplasia)
Could effect protein function

Question 16

What is a Nonsense mutation?

Answer 16

A change in nucleotide sequence that results in premature stop codon caused by point mutations and frameshifts

Question 17

What does Nonsense mutations result in?

Answer 17

Non-functional protein
PAH mutation in BMPR2 gene
Duchenne muscular dostrophy- dystrophin gene

Question 18

What are Insertions/Deletions?

Answer 18

Remove 1 to millions of nucleotides
5-10% all mutants
50% DMD
frame shift
a-thalassemias associated with melenoma

Question 19

What Instrument can you Identify Gene mutations on?

Answer 19

Electropherogram

Question 20

What are the features of Pulmonary Arterial Hypertension?

Answer 20

Intimal fibrosis
Direction of blood flow
Media thickening

Question 21

What are Expanding trinucleotide repeats?

Answer 21

Simple tandem repears, during replication increase in copy number
- 17 diseases include huntingtons diseas

Question 22

What happens in Huntington Disease?

Answer 22

• CAG repeats encode a poly-glutamine region
• In IT15 gene encoding huntington protein consists of 6-35 repeats
• 36 or > causes neurodegenerative disease
• raises ethical issues during genetic screening

Question 23

What are Transposons?

Answer 23

Sequence of DNA that can move around the genome act as recombination hotspots

Question 24

What are the 3 Types of Transposons?

Answer 24

Retrotransposonss - ‘copy and paste’
DNA transposons - ‘cut and paste’
Alu Repeats- most abundant, in LDL receptor for pathogenic deletions, also removes bad cholesterol eg FH

Question 25

What is an advantage of Selective pressure in a Malaria case?

Answer 25

Selective pressure for erythrocytes with sickle cell haemoglobin mutation can provide protection against malaria

Question 26

What is the distinct characteristics Cancers acquire in mutations?

Answer 26

Mutations are selected as they proliferate more and accelerate mutation rate

Question 27

What is Haploinsuffiency?

Answer 27

we all have 2 copies of a gene (diploid) , this is when one copy is deleted or inactivated by a mutation so only one copy is functioning

Question 28

What Happens in Haploinsuffiency?

Answer 28

- The loss of function mutation tends to be recessive for 2 reasons - feedback loops & 50% gene sufficient - dosage effect may be seen as gene part of signalling system and competes to determine metabolic switch - gene products need a&b globin to make thalassemia (anaemia)

Question 29

What is Human Genetic Variation?

Answer 29

single nucleotide changes where 25% are structural changes in copy numbers

Question 30

What is Penetrance?

Answer 30

how frequently the disease is manifested