Mutations Flashcards
Define mutation (2)
A heritable alteration in a gene or chromosome (change in nucleotide sequence)
The process that produces alteration (source of alleles - driver of evolution)
What is a transposable element?
Specific DNA sequences that don’t have fixed position in the genome - they transpose as a distinct unit to random, discrete sites (reversible)
Transposable elements make up how much of the genome?
~50%
What type of micromutations change the open reading frame?
Deletions and insertions
What is a transition mutation?
When a single nucleotide changes to the same type of base
Purine to purine(A-G)
Pyrimidine to pyrimidine (T-C)
What is a transversion mutation?
A single nucleotide change that results in a different base type
Purine to pyrimidine
Pyrimidine to purine
A/G- C/T
What is a missense mutation?
A base substitution that changes the amino acid
What is a silent/neutral mutation?
A base substitution that results in no amino acid change
What is a non-sense mutation?
Early incorporation of a stop codon due to frame shift
What is a protoncogene?
Normal version of a gene which encodes protein involved in regulation of cell growth and differentiation
Why are gain of function mutations often dominant?
Because they influence the normal function, and a change is seen.
Why are recessive mutations often loss of function?
Because the normal 50% of alleles still produce normal protein - so still normal function
Does mitochondrial DNA suffer germline or somatic mutations?
Both
What are some of the common symptoms of mitochondrial disease?
Muscle weakness, movement problems, diabetes, kidney failure,heart disease, vision abnormalities
What are primordial germ cells?
Common origins of spermatozoa and oocytes - ancestor of their germline
When does spermatogenesis begin?
At puberty
What results from a mutation in early embryogenesis?
A mosaic - 2 or more populations of cells in the same individual
Generally, recessive mutations are loss of function and effect ________________
Biochemical pathways
Generally gain of function mutations (dominant) cause _________________
Structural abnormalities
What is a reciprocal translocation?
Two break arrangements
May be balanced (all DNA present) or unbalanced (DNA lost/gained)
How are reciprocal transactions assessed for imbalance?
Segregation analysis using pachytene diagram
What is robertsonian translocation?
Two acrocentric chromosomes fused together
Carriers of robertsonian translocations have _________ phenotype
Normal
Robertsonian translocation carriers produce offspring with ……..
Either monosomy or trisomy
What are the negatives of microarray comparative genomic hybridisation (aCGH)? (4)
- does not detect balanced rearrangements
- mosaicism may be missed
- more expensive than katyotyping
- copy number variation
What are the advantages of aCGH?
- entire genome examined at high resolution
- targeted against known genetic conditions/subtelomere regions
- one array is equivalent of many 1000s FISH
- detailed info on genes in deletion/duplication region
What conditions is aCGH primarily used for?
Visible phenotypes
- learning difficulties
- developmental delay
- multiple congenital abnormalities
What is uniparental disomy (UPD)?
Presence of homologous chromosomes from one parent
What is isodisomy and how is it caused?
When an individual has two identical chromosomes from one parent.
Caused by an error meiosis 2
What is heterodisomy and how is it caused?
When an individual has two homologous chromosomes from one parent
Caused by an error in meiosis 1
What’s the most common cause of UPD?
Trisomy rescue - non disjunction event in meiosis causes trisomy then a post zygotes mitosis error leads to UPD embryo
