What is Trisomy 13?
Patau Syndrome - rare genetic condition caused by the duplication of chromosome 13.
- Increasing risk with maternal age
- Spontaneous error
Symptoms of Trisomy 13
Facial abnormalities Eg. cleft lip, small eyes, low set of ears
Neurological issues: Holoprosencephaly (small head, failure of brain to divide properly), heart defects, dysmorphology, kidney defects
Meiotic non-disjunction
Chromosomes that have failed to divde properly during formation of eggs or the sperm.
Cri du chat syndrome / 5p monosomy
Deletion of a part in the 5p chromosome. This is due to the homologous recombination between areas of concentrated repeated squences, resulting in deletion or duplications of the chromosome.
*difficult to analyse under the microscope compared to trisomy 13
What determines the severity of cri du chat syndrome?
How large the short deletion is on the 5p chromosome
Single gene disorders
A rare condition caused by individual mutant genes. Recessive, dominant or X-linked disorders (affect males more severely)
Exhibit pedigree patterns (inheritance through a family) - help predict the likelihood of the disorder occurring in future generations
What are the two substitution mutations?
- Transition (more common 2/3 mutations):
Purine is substituted with purine
Pyrimidine with pyrimidine
Eg. often triggered by UV damage in cancer. - Transversion (less common 1/3 mutations):
Purine is replaced by pyrimidine
Vice versa
3 classes of substitutions: What effect does it have on the amino acid sequence?
- Synonymous ‘silent’ mutations
- no change in amino acid sequence - Nonsense mutations (non synonymous)
- replacement of amino acid with a stop codon - Missence mutations non synonymous)
- replacement of amino acid with another amino acid
(a) conservative: minimal effect because replacement is similar
(b) non-conservative: serious effect because replacement is dissimilar
Non-synonymous:
Replacement/ alter of amino acid sequence
Pathogenic mutations occur in
- Mutations in protein coding regions (exons)
- Mutations disrupting RNA splicing/stability
- Mutations affecting gene regulation/dosage
Frameshift mutations
Insertion or deletion of base/bases
Results in an entirely different sequence of amino acids. Usually ends with a premature truncation of the protein.
Usually associated with severe phenotypes.
Cystic fibrosis is an example of what inheritance?
Autosomal recessive inheritance
Needs to have two copies of mutated gene for child to have the mutation.
Example of a autosomal dominant disease:
Myotonic dystrophy: inability to relax the muscle.
What does it mean by having a unaffected carrier?
There is one normal gene and one faulty (mutated) gene for a specific recessive genetic condition. The normal gene overrides the mutated gene, therefore doesn’t show signs of the condition.
Y linked dominant:
Only affects males
Affected males always have an affected father.
X-linked inheritance:
Males have a single X chromosome and females have two X’s which one is inactive
X-linked recessive inheritance
- Incidence is much higher for males
- Heterozygous females are usually unaffected due to one inactivated X gene
An affected male will pass on the gene to all of his daughters, who will be carriers - cannot pass the gene to his sons (Y)
X-linked dominant inheritance
- Doesn’t skip generations
- Affected females is x2 common than affected males.
- Both male and female offspring of female carriers have a 50% risk of inheriting the phenoty[e
