Types of mutations and their effects? Flashcards
(11 cards)
Missense mutation?
Change to nucleotide sequence which causes an amino acid substitution.
Nonsense mutation?
Change to nucleotide sequence which causes the introduction of a Stop codon.
Synonymous mutation?
A change to nucleotide sequence which does not alter the final amino acid sequence.
What is a pathogenic variant?
Non-pathogenic variant?
DNA sequence of an allele is altered such that it increases predisposition/leads to a diseased phenotype by encoding a protein with defective function.
An altered sequence of an allele which does not predispose or lead to an diseased phenotype as protein function is not defective.
Details on the human genome?
20,000 genes
3.2 billion bp
22 autosomal pairs, 1 pair of sex chromosomes.
8-10 exons per gene…
What causes down syndrome?
Why can survive vs others?
Trisomy 21 produces viable humans.
C21 is smallest chromosome, with fewest base pairs and low gene density
= less imbalance.
Few genes involved in crtiical developmental and metabolic pathways.
Chromosomes fail to segregate during meiosis metaphase 1.
= Non-disjunction - homologous pairs of chromosome 21 don’t separate.
Mouse details?
Mice contain 21,000 genes, with 2.7 billion bp.
Gestation lasts for 20 days, with many gestations possible simulatenously (5/6)
= Much faster reproductive cycle than humans.
19 pairs of autosomes, and a pair of sex chromosomes.
Drosophila details?
Reach sexual maturity in 10-14 days = Rapid life cycle.
Massive reproductive rate = hundreds of eggs.
Genome is 135 million bp, within 4 pairs of chromosomes.
Sex determination via ratio of X to autosomes.
Yeast details?
Unicellular, eukaryotes.
12 million bp, including 6000 genes.
16 chromosomes - 25% homology to humans.
Mating types a and alpha.
Sex determined by C11 locus.
Where might non-exonic mutations lead to disease?
Intron sequences = particularly on intron/exon borders.
= Altered splicing producing incorrect splice variants,
Change to nucleotide sequence can affect splicing, and lead to exon skipping.
Or alternatively,
splice site mutation may lead to failure to recognise splice site in intron and so it is included in new CDS.
= Change to function!
Distant regulatory elements like silencers and promoter regions:
May lead to enhanced promotion or silencing, or failure to promote or silence = change to EXPRESSION but not to function.
Promoter region = reduced expression of protein, but with NORMAL FUNCTION.
5’ UTR = upstream of start codon, where exon is not incorportated into protein sequence…
= Ribosomal recruitment site = altered affinity for ribosomes = affect translation and expression!
3’ UTR = contains sequence for Poly-A tail in mature mRNA to stabilise during translation and may contain mRNA localisation sequence (to Rough ER for example)
= May lead to reduced mRNA stability, degradation and localisation to wrong compartment.
What is the CDS?
What is the TSS?
the CDS runs from the start codon (AUG) to the stop codons.
It includes the exons which are incorporated into the mature mRNA and typically excludes the first exon in the 5’ UTR.
= Does not include introns, 5’ and 3’ UTRs…
TSS is the transcription start sequence, where first RNA nucleotide incorporated by RNA pol II.
(It is a distinct site, and is not the start codon!!!!) = usually in 5’ UTR
