Clinical Genetics in Paediatrics Flashcards
Uses of a standard karyotype?
Search for:
• Aneuploidy
• Chromosomal translocation
• Deletions
Uses of FISH?
Search for:
• Deletions
• Microdeletions
Uses of PCR amplification and sequencing?
For point mutations
Uses of aCGH?
Aneuploidy, chromosomal translocation, deletion, microdeletion
Uses of Next Generation Sequencing?
Deletions in part of a gene and point mutations
Principles of what aCGH allows?
Allows identification of regions in the genome that have been deleted or duplicated, by comparison with a control DNA sample
Describe results of aCGH
Each dot on a microarray represents a specific genetic region:
• If more patient DNA than control DNA hybridises to the dot - patient duplication
• If less patient DNA than control DNA hybridises to the dot - patient deletion
What can aCGH not be used?
It only detects chromosomal imbalance, not balanced translocations
How many bases need to change to cause a genetic disease?
Only 1 NEEDS to change
How many polymorphisms are there in an average person?
4,000,000
6 points to consider when trying to determine if the genetic change causes disease?
- It is in a gene that matches the phenotype
- It has an effect on gene function
- It is not listed as a polymorphism
- It is in an evolutionarily conserved area of the gene
- It is de-novo in the child
- It is present in other affected family members
Difference between implications of de-novo and inherited?
If it is inherited, it is more likely to be a polymorphism
If it arose de-novo, it is more likely to be causative mutation
Evidence that a mutation is causative?
It is in the right gene (assoc. with the phenotype)
Has the right effect
Found in affected (not unaffected) people; beware of penetrance
Biological evidence
Examples of genetic disorders that cause learning difficulties?
William’s syndrome
Rubinstein–Taybi syndrome (tip of nose hangs down and half-moon eyes)
Basic definition of intellectual disability?
Children/young people who have either a learning difficulty in relation to acquiring new skills OR who learn at a different rate to their peers
