Molecular Genetics Flashcards
What does genetic variation result in
Different phenotypic characteristics
How does genetic difference exist
Between individuals within or between different populations
What is the scale of variation
From gross alterations in the human karotype to single nucleotide changes
What are the 2 types of variations
. Polymorphisms
. Disease causing mutations
How much DNA do we share with each other
99.9%
What does genetic variation lead to
Evolution
Species evolved due to mutations in genetic code
Most mutations do not have an effect on us - lead to phenotypic differences - genetic variation - slightly different
What are the types of mutations
. Point mutations
. Frameshift mutations
Point mutations
Single nucleotide base is changed, inserted or deleted from a sequence of DNA or RNA due to a simple mistake during DNA replication in meiosis
Result in often little consequence, sometimes severe consequences
e.g. sickle cell anaemia
Frameshift mutations
Caused by a deletion or insertion or inversion in a DNA sequence that shifts the way the sequence is read
Such mutations are more dangerous and change the codon
What can some mutations lead to
Disease
Non - functional proteins = damaging phenotype - no evolutionary benefit = disease causing mutations
Alter reading of codons in transcription/translation = protein chain at end is significantly different
What type of mutation has a more serious consequence
Frameshift mutations
What percentage of the population have Polymorphism
> 1%
Very abundant
What is Polymorphism unlikely to be causative of
Genetic disease
It causes variation in normal phenotype, sometimes but not always
What is the consequence of polymorphisms?
Can affect disease predispoistion, progression or drug response, when combined with other genetic and environmental factors ( disease risk factor )
Why are polymorphisms unlikely to be caused by genetic disease
- As you wouldnt find in such abundance
- Evolution took disease causing mutations out of the gene pool, if it was disease causing, it would lead to evolutionary deficit = taken out of gene pool
- Affect progression of diseases - risk factors - association with specific diseases and affect how you respond to different drug combinations = influence over diseases but most of them cause natural variation
What are the 4 common types of polymorphism?
- SNPs- single nucleotide polymorphism - point mutations
- Indels - small insertion/deletions
- Large scale copy number polymorphism - CNPs or CNVs
- Tandem repeats
What are tandem repeats
Larger regions of nucleotide material that can be repeated throughout genetic code
A sequence of nucleotide can be repeated numerous times in sequence
what is the most common type of polymorphism?
SNPs
make up 80% of the 0.1% difference between individuals
What is SNP
- Point mutation
- Single nucleotide substitution of nucleotide with another
Where can SNPs occur
Anywhere on genome in DNA strand 1. Within gene . Coding ( exons ) . Non-coding ( introns) 2. Between genes . Non-coding ( intragenic region )
Where is it more frequent for SNPs to occur and why
Within non-coding region due to selection pressure
Less likely to cause abnormal functioning protein if not active in region of DNA strand that codes for protein itself
During RNA splicing, non - coding regions do play role in transcription factor binding and RNA splicing of specific genes - influence over proteins
Do SNPs change phenotype
- Most SNPs are neutral with no phenotype change
- 3-5% have a functional role and do not change phenotype - variation by v.small amount
Types of SNPs
. Synonymous - codes for the same amino acid - by chance it could be a mutation which changes it for another nucleotide which by chance codes for same a acid when read as triplet = NO EFFECT
. Non-synonymous - alters the poly peptide chain
which has 2 possibilities
1. Missense mutation - alters amino acid sequence
2. Nonsense - results in premature stop codon - resulting in a shorter polypeptide chain = non functional protein
What may SNPs in non coding regions do
May alter gene splicing/transcription factor binding/regulation
What are Indels
Insertion or deletions of nucleotide sequences of 2-10,000 base pairs
What is 2nd most common polymorphism
Indels
What type of mutation occurs in indels?
Frameshift mutation
2 - 10,000 base pairs
What are the 2 types of tandem repeats
- VNTRs - Variable Number Tandem Repeats
aka mini-satellites - 10-100 base long segments repeated - STRs ( Short tandrem repeats )
aka micro-satellite ( smaller ) - 2-9 base long segments repeated ( fragment lengths )
Where are Tandem repeats found
Throughout genetic code but have little consequence
Non coding regions
Use of tandem repeats
DNA fingerprinting - match it up
What are CNPs
Entire gene duplicated or deleted within genetic code
Larger number of nucleotides repeated
How is a polymorphism different from a mutation leading to a specific disease ?
- It is due to the prevalence in population
-If mutation is found in <1% of population = mutation
-If mutation leads to loss of function or aberrant levels of normal protein or mutant protein its a disease causing mutations
THESE ARE NOT REFERRED TO AS POLYMORPHISMS
Where do disease mutations often occur
In exons