17. Mutations (b) Flashcards
What would a sweat test result of Na+ 87mmol/L confirm?
A suspected case of cystic fibrosis.
What can cause complications with finding the genetic cause of CF?
The sufferer could be a compound heterozygotes for two different CFTR mutations.
What do pre-natal diagnostic tests rely on?
The mutations of the sufferer in the family being identified.
What mutation is the most common cause of CF?
p.F508del = phenylalanine is deleted at amino acid 508 of the CFTR-encoded protein.
What is the second most common cause of CF?
p.Gly551Asp
In the UK, how many CF mutations are routinely screened for in genetic testing?
The 29 most common. Then an expanded panel of 97 additional tests (126 mutations screened for). Uses multiplex PCR-based test.
How do SSCP (single strand conformation polymorphism) mutation scans work?
The amplified DNA is heated to denature and then cooled rapidly. The strands adopt sequence-specific partly double-stranded forms. The DNA is electrophoresed in polyacrylamide gel and detected by staining silver.
What could explain three mutations found in a CF sufferer?
Two disease causing mutations and one natural variant from the parent that’s unrelated to CF.
Give the details of amniocentesis.
It’s performed at 15-20 weeks gestation, under ultrasound guidance. Cells need to be recovered and cultures for two weeks. There is a 0.5-1% risk of causing miscarriage.
Give the details of chorion villus biopsies.
Performed at 10-13 weeks gestation, under ultrasound guidance. Sample taken trans-cervically or trans-abdominally. The foetal villi has to be separated from the maternal tissue. There is a 2% risk of miscarriage.
How can the copy number of many exits in parallel be counted?
Using multiplex ligation-dependent probe amplification.
What is looked for in MLPA graphs?
Where the height of a peak is halved, which shows that for one allele gene, there is a mutation that prevents annealing so half does not anneal, these bits have a deletion mutation.
What theory explains why inherited cancer genes have recessive mutations but display dominant inheritance?
Alfred Knudson’s two-hit theory.
