Genetics in child diseases Flashcards
How many base pairs are there in the human genome ?
3,000,000,000 base pais
How many genes make a human ?
30,000
How many polymorphisms do you find on average in a person ?
3,000,000
What is Chromosome Microarray - Array genomic hybridisation?
Allows you to look for sub-microscopic deletions or duplications of chromosome material across the whole human genome
Whta is the use of FISH?
usually to analyse cancer
How do babies look like when they are first born?
Squished and like their dads (to prevent them from eating it xD llol)
What is the first test to check for genes?
Array - as it is more sensitive
Why is karyotype not preferred?
as they look quite similar and is different to pick up details
What does Next generation Sequenes do?
sequence a little panel of the genes
What is considered normal?
a. The commonest form of gene sequence
b. The form of sequence that doesn’t cause disease
c. The sequence of Frederick Sanger (d.2013)
d. The Sequence of Frances Crick
e. You
the commonest form of gene sequence
What is the biggest problem with genomewide analysis ?
Data files big
Identification of many polymorphisms
Data interpretation is complex
What percent of the genome acutally codes for anything?
1-3%
How do we know if the info from exons are important or not?
if a variation/ polymorphism is present in the data base , higher chance it doesnt cause a disease
How do we know a 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 bit of gene
It is de-novo in child – if only child is affected
or
It is present in other affected family members
If a mom has it and the children have the same mutation?
polymorpohism
A pattern that you can recognise
syndrome
Very drooly for 9 year old, round eyes and odd eye brows
Kabuki makeup syndrome
What are the features of Kabuki Makeup syndrome?
speech delay cleft palate unusual ayeyes and eyebrows tendency to drool Short 2nd phalanges of 5th finger
The mutated gene in Kabuki syndrome
Heterozygous for mutation in MLL2
What does the mutation in Kabuki do?
the splice site is abolished
How likely is it to find a causative mutation in a child with a severe developmental disroder with next generation sequencing?
30%
What is the best test for identifying de novo mutations?
Next generation sequencing with clinical assessment
What is the best test for identifying developmental disorders/ de novo mutations?
Next generation sequencing with clinical assessment
What is spinomuscular atrphy?
recessive genetic condition
type II - less serious
adenurophysis mRNA gene - treatments that involve gene splicing (intrathecal injections)
How is PKU identified?
Screened for
How do we treat tuberous sclerosis?
Rapamycin targets mTor signalling
Which test is used to test for genetic imbalances, and t sequence the entire genome?
Array
Why are arrays preferred over NGS?
Cheap!
They can sequence the entire genome/ genome-wide
Can look for imbalances
usually done on everyone
When is NGS used?
To check for point mutations in exons only
Usually 2nd line to array if you didn’t find anything specific in an array
**1st line in neonates who are floppy, and they haven’t found a cause
more expensive
Which test is the best to look for developmental disorders?
NGS and examination
