Genetics in children Flashcards
What tests are genome wide testing?
Array genome hybridisation
Exome enriched next generation sequencing
Whole genome sequencing
What is the human life cycle?
Infertility Antenatal Neonatal Paediatric Adult onset
How big is the human genome?
3,000000000 base pairs
30,000 genes
3,000000 polymorphisms
How is an aneuploidy tested?
Entire chromosome affected so it is a standard karyotype
How is a chromosomal translocation tested (100 megabases)
Standard karyotype
How is a chromosomal deletion tested (10 megabases)
Fluorescence in situ hybridisation and a karyotype
How is a microdeletion tested (5 megabases)
Fluorescence in situ hybridisation
How is a deletion of part of a gene tested (1000 bases)
Multiplex: ligation dependant amplification
How is a point mutation tested (1 base)
PCR amplification and sequencing
What is the purpose of a chromosomoe microarray genoic hybridisation?
Allows you to look for sub-microscopic deletions of duplications of chromosome material across the whoel genome
What is the patients DNA compared with?
Control DNA
What will half as much DNA in comparison with the control DNA suggest?
Deletion
What will 50% more DNA in comparison with the control DNA suggest?
Duplication
What type of chromosome rearrangements with chromosome microarray detect?
Unbalanced chromosome rearrangements
What is DiGeorge syndrome?
Deletion of a portion of gene from the q arm of chromosome 22
How is DiGeorge syndrome inherited?
Autosomal dominant
What genetic test is done for DiGeorge diagnosis?
Array comparative genomic hybridisation
What is an intronic variant?
Low likelihood of effect
What is an exonic variant?
Potential to change amino acid sequence, create a stop, cause a frameshift or have no effect at all
What can cause a splicing error?
Change to splice sequence 1 or 2 bases into intron
How do you know that a genetic change causes disease?
Gene matches phenoctype Has an effect on gene function Not listed as a polymorphism Evolutionary conserved bit of gene De-novo in child Present in other affected family members
What are the different types of mutations in DNA sequences?
Wild type Stop Missense Insertion Deletion (out of frame) Deletion (in frame) Triplet expansion
How are phenotypes identified?
Dysmorphology database
Pubmed
Online mendelian inheritance in man
Other geneticists
What is the phenotype of kabuki makeup syndrome?
Cleft palate
Unusual eyes and eyebrows
Tendency to drool
Short 2nd and 5th finger
What is the genotype in kabuki makeup syndrome?
Mutation in MLL2 which is a protein that makes histones
Produces a stop codon creates a non-functional protein
What is the best test for de-novo mutations?
Next generation sequencing with clinical assessment
How is Kabuki syndrome inherited?
Autosomal dominant
How can spinomuscular atrophy be treated?
Treatments that improve gene splicing
How can tuberous sclerosis be treated?
Rapamycin targets mTor signalling
