Chromosome Abnormalities/Mutations/Analysis Flashcards
Give the three main types of chromosome abnormalities
Numerical
Structural
Mutational
Give types of numerical chromosome abnormalities
Non-disjunction
Autosomal aneuploidy
Sex linked aneuploidy
Describe the mechanism of non-disjunction
Problem in meiosis to give a disomy (two copies of a chromosome in a daughter cell/gamete)
What does non-disjunction give rise to in offspring?
Trisomy (an extra chromosome in a cell)
What is caused by trisomy in chromosome 21?
Down syndrome
Trisomy in chromosome 13?
Patau syndrome
Chromosome 18?
Edwards syndrome
Chromosome 45,X?
Turner syndrome
Chromosome 47,XXY?
Klinefelter syndrome
Give some features of Patau syndrome
- dysmorphic features
- mental retardation
Features of Edwards syndrome?
- developmental problems
Features of Turner syndrome?
- female
- short stature
- neck webbing
- widely spaced nipples
Features of Klinefelter syndrome?
- male
- infertile
- small testes
- tall
- long limbs
Give types of structural chromosome abnormalities
Balanced/unbalanced reciprocal translocation
Robertsonian translocation
Inversion
Deletion
Insertion
What is reciprocal translocation?
Chromosome breaks in two and forms two new derivatives
Balanced - same amount of each at the end; phenotypically normal
Unbalanced - from normal parent and another with balanced translocation; gives rise to trisomy/monosomy in offspring
What is Robertsonian translocation?
Occurs in acrocentric chromosomes;
- long arms (q) attach to long arms
- short arms (p) attach to short arms
Gives rise to abnormalities in offspring if they receive unequal amounts of a chromosome
Give two types of inversion
Paracentric inversion - abnormal fixing, no centromere involvement
Pericentric inversion - abnormal fixing in the centromere region
Give the four types of mutational coding abnormalities
Silent
Missense
Nonsense
Frame shift
What is the difference between transitions and transversions?
Transitions - purine mutates to purine, pyrimidine mutates to pyrimidine
Transversions - purine mutates to pyrimidine, pyrimidine mutates to purine
Give types of mutational chromosome abnormalities
Germline/somatic
Gene disruption
Polymorphism
*All may be coding/non-coding/point mutations
Give the main types of abnormality detection
PCR
ARMS
RFLP
DNA sequencing
What is PCR?
Polymerase chain reaction
What happens during PCR?
- denaturation to create a single-stranded DNA
- annealing (bonding of primers to DNA template
- extension of primers using DNA polymerase to synthesise new DNA strands behind them
- repetition to amplify target DNA
- analysis using gel electrophoresis
What is ARMS?
Amplification refractory mutation system
What happens during ARMS?
- sequence specific primers will only amplify if the target allele is present
- wild type allele amplified by a normal primer
- mutant allele amplified by a mutant amplification
- then undergoes PCR and gel electrophoresis
What is RFLP?
Restriction fragment length polymorphism
What happens during RFLP?
- restriction enzyme cuts DNA strand at different lengths
- gel electrophoresis
What is DNA sequencing?
the process of determining the precise order of nucleotides within a DNA molecule
How does DNA sequencing work?
- double helix denatured
- one strand isolated
- radioactively labelled primer used to replicate strand
- primer elongates to match strand and reform a double strand (stops at ddNTP)
- gel electrophoresis (coloured dye shows up)
