[FMS] MCG - intro to genetic variation Flashcards
what is polymorphism?
Polymorphism is defined as the presence of two of more variations in a DNA sequence
what are the 4 types of polymorphism
single, SNPs
Insertion-deletion
Tandem
Structural
What determines the type of polymorphism?
- The nature of the sequence determines the type of polymorphism and its functional impact.
- Often no direct functional effect.
what is a mutation?
change in sequence
the process generating sequence changes
what is an SNP
Single base substitutions that occur throughout the genome
what is the most abundant type of polymorphism in the body
SNPs
when do SNPs occur
Occur once in every 1-2kb
most SNPs are in what section?
non coding region
what is a haplotype
A haplotype refers to a limited set of DNA variants (polymorphisms) along a single chromosome that tend to be inherited together (close together).
what is a genotype
Two alleles present at a SNP in an individual.
are close SNPs independent
Close SNPs are not independent.
what is linkage disequilibrium
Linkage disequilibrium is the non random association of alleles at different loci in a given population.
what is tandem repeat polymorphism
They are repeat elements with non-coding DNA.
what are the 3 types of polymorphic repeats?
-
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
What are 2 diseases caused by tandem repeat polymorphism?
Huntington’s disease
Friedreich’s Ataxia
what kind of disease is huntingtons?
- Autosomal dominant
- Abnormal protein neurotoxic
what repeat is presented in huntingtons
Trinucleotide CAG repeat in exon 1 ofIT15 (Huntingtin)
how many CAG repeats must you carry to have huntingtons disease
Carrying over 40 repeats leads to Huntington’s disease
Carrying less than 36 repeats gives no increased risk
what kind of disease is Friedreich’s Ataxia
Autosomal recessive
what repeat does Friedreich’s Ataxia have
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
what are 3 types of structural variation in chromsomes
- 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.
What was the first disease system to be related to structural variation in the genome?
Charcot-Marie Tooth
what is the heidy weinberg equation
p2 + 2pq + q2 = 1
- p2– homozygous p
- 2pq – heterozygotes
- q2– homozygous q
what are the 5 assumptions needed for HWE to hold in a population
- Large population
- No migration
- No new mutation
- No selection
- Random mating
Why do all genetic variants experience a change in frequency over time?
All genetic variants will change in their frequency over time, due toGenetic Drift(= random change)
What is selection in genetics?
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)
What is a population bottleneck?
Sudden population shrinkage (bias against harmful recessive alleles)
what 3 things causes a change in allele frequency
- genetic drift
- selection
- population bottleneck
how was the lactase gene selected for?
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.
what kind of disease is sickle cell disease and what is sickle cell disease caused by?
Recessive disease caused by a SNP in Haemoglobin Beta gene
(HBB)
what is the sickle cell mutation
GAG to GTG recoding glutamate to valine
β6Glu→Val on translation results in HbS (α2βs
2)
Describe the monogenic vs polygenic model.
- The frequency of risk alleles in a population is across the bottom.
- How much risk the individually convey is on the Y-axis.
