Genetic variation Flashcards
What is Ellis-Van Creveld Syndrome?
Autosomal recessive condition
What is the typical different between 2 genomes?
3 million SNP (0.1% of total 3.2 billion base pairs)
What is the human genome project?
1990-2003
-Complete mapping and understanding of all genes of human beings.
What are introns?
DNA that does not code for proteins (removed by RNA splicing)
Exons (coding) = 1.5% of genome
How are exons bonded to eachother?
covalently
what % of the genome are genes (exons/ introns)
25%
What are the characteristics of hereditary variants?
- Inherited from a parent
- Present throughout life / in every cell
- Present in egg/sperm cells
What are characteristics of acquired variants?
- Occur at some time during a person’s life
- Only in certain cells
- Not passed down
What are microsatellites?
- Repeats of short segments
- 1-10 Nucleotides
- Prone to mutations due to slippage
- mutation rates at micros > SNP
What are structural variations?
- Large scale genomic variation >1KB
- Chromosomal abnormalities e.g. inversion
- Aneuploidy
Define polymorphism
- DNA sequence variation common in the population (>1%)
- Two or more acceptable alternatives
Explain single nucleotide polymorphisms
simple type of mutations: 3 types: substitution, deletion &, insertion (point mutation)
When can SNP be detected?
- Phenotypic level
- Restriction fragment level
- Sequence level of DNA
What are tandem repeats?
-Very unstable
-repeating sequence that lies next to each other
-
How do repeat polymorphisms occur?
Addition/deletion of entire repeat units
What is the difference between microsatelittes & minisatellites?
Micro: 1-10 nucleotides
Mini: >10 nucleotides
Explain strand-slippage replication
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
How does huntington’s disease occur?
- Micro-satellite instability
- Repeat of CAG codon
- Excess glutamine
- Progressive disease
- Severity depends on repeat count
Explain copy number variation
chromosomal deletions/ duplications which involve large stretches of DNA
Can result in advantages (AMY1) or disease (psychiatric disorders)
What is the relationship between AMY1 & evolution?
-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
What is PTPN6 responsible for?
- early onset emphysema due to variant: ala455Thr
- genetic variants with larger effect sizes more likely to be found in familes
Explain Thalassemia
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
Explain sickle cell anaemia
- Abnormal red blood cells
- Do not last (anaemia)
- Caused by mutation in HBB gene
- Needs 2 copies
- Abnormal gene in chromosome 11
