[FMS] MCG - intro to genetic variation

Question 1

what is polymorphism?

Answer 1

Polymorphism is defined as the presence of two of more variations in a DNA sequence

Question 2

what are the 4 types of polymorphism

Answer 2

single, SNPs
Insertion-deletion
Tandem
Structural

Question 3

What determines the type of polymorphism?

Answer 3

• The nature of the sequence determines the type of polymorphism and its functional impact.
• Often no direct functional effect.

Question 4

what is a mutation?

Answer 4

change in sequence

the process generating sequence changes

Question 5

what is an SNP

Answer 5

Single base substitutions that occur throughout the genome

Question 6

what is the most abundant type of polymorphism in the body

Answer 6

SNPs

Question 7

when do SNPs occur

Answer 7

Occur once in every 1-2kb

Question 8

most SNPs are in what section?

Answer 8

non coding region

Question 9

what is a haplotype

Answer 9

A haplotype refers to a limited set of DNA variants (polymorphisms) along a single chromosome that tend to be inherited together (close together).

Question 10

what is a genotype

Answer 10

Two alleles present at a SNP in an individual.

Question 11

are close SNPs independent

Answer 11

Close SNPs are not independent.

Question 12

what is linkage disequilibrium

Answer 12

Linkage disequilibrium is the non random association of alleles at different loci in a given population.

Question 13

what is tandem repeat polymorphism

Answer 13

They are repeat elements with non-coding DNA.

Question 14

what are the 3 types of polymorphic repeats?

Answer 14

• Microsatellites
  
  • (short tandem repeats) (CA)^nor CACACACACACACA
• Minisatellites
  
  • Repeat unit is 10-60 base pairs long Application as original DNA fingerprinting
• Triplet repeats
  
  • Role in several neurogenetic disorders - located close to causal gene

Question 15

What are 2 diseases caused by tandem repeat polymorphism?

Answer 15

Huntington’s disease

Friedreich’s Ataxia

Question 16

what kind of disease is huntingtons?

Answer 16

• Autosomal dominant
• Abnormal protein neurotoxic

Question 17

what repeat is presented in huntingtons

Answer 17

Trinucleotide CAG repeat in exon 1 ofIT15 (Huntingtin)

Question 18

how many CAG repeats must you carry to have huntingtons disease

Answer 18

Carrying over 40 repeats leads to Huntington’s disease

Carrying less than 36 repeats gives no increased risk

Question 19

what kind of disease is Friedreich’s Ataxia

Answer 19

Autosomal recessive

Question 20

what repeat does Friedreich’s Ataxia have

Answer 20

Trinucleotide GAA repeat in intron 1 ofFXN (Frataxin)

• Repeat diminishes expression of Frataxin
• Frataxin - mitochondria, binds iron, required for mitochondrial function

therefore its a type of MITOCHONDRIAL DISORDER

Question 21

what are 3 types of structural variation in chromsomes

Answer 21

• Segmental duplication: segments of DNA that contain several genes are duplicated between different people.
• Multiallelic CN variant: Where you get copying from one chromosome to another. So meiosis is affected so that you get two copies from one parent in that particular region.
• Deletion events: Delete a particular segment.

Question 22

What was the first disease system to be related to structural variation in the genome?

Answer 22

Charcot-Marie Tooth

Question 23

what is the heidy weinberg equation

Answer 23

p2 + 2pq + q2 = 1

• p2– homozygous p
• 2pq – heterozygotes
• q2– homozygous q

Question 24

what are the 5 assumptions needed for HWE to hold in a population

Answer 24

• Large population
• No migration
• No new mutation
• No selection
• Random mating

Question 25

Why do all genetic variants experience a change in frequency over time?

Answer 25

All genetic variants will change in their frequency over time, due to **Genetic Drift** (= random change)

Question 26

What is selection in genetics?

Answer 26

The process by which certain traits become more prevalent in a species than other traits. Its characteristics include: - Acts on top of random drift - Bias to immune-related genes - Usually leads to much faster changes in allele frequencies over time - Leads to increase in frequency of one allele in the population (can be localized)

Question 27

What is a population bottleneck?

Answer 27

Sudden population shrinkage (bias against harmful recessive alleles)

Question 28

what 3 things causes a change in allele frequency

Answer 28

- genetic drift - selection - population bottleneck

Question 29

how was the lactase gene selected for?

Answer 29

The gene responsible for digesting lactose is called LCT. Most people naturally lose the ability to digest lactose as they age. In northern Europe, mutations in the MCM6 gene emerged - These mutations control the LCT gene. These mutations were beneficial for people with a pastoral lifestyle (cattle farming). It helped them digest milk better. There was a powerful natural selection for these mutations.

Question 30

what kind of disease is sickle cell disease and what is sickle cell disease caused by?

Answer 30

Recessive disease caused by a SNP in Haemoglobin Beta gene (HBB)

Question 31

what is the sickle cell mutation

Answer 31

GAG to GTG recoding glutamate to valine β6Glu→Val on translation results in HbS (α2βs 2)

Question 32

Describe the monogenic vs polygenic model.

Answer 32

- The frequency of risk alleles in a population is across the bottom. - How much risk the individually convey is on the Y-axis.