What is the first step in the central dogma of making a protein from a gene?
- transcription
- splicing
- translation
- post-translational modification
- protein transport
Transcription
Next gen sequencing of genes has an advantage over convetional Sanger sequencing because…
- it will identify a large number of polymorphisms
- each sequence read is more accurate
- it is cheaper to sequence a single gene
- it will analyse a single gene more efficienctly
- it allows sequencing of a much larger number of genes
it allows sequencing of a much larger number of genes - NGS allows for sequencing of many more genes compared with conventional sequencing
Array Comparative Genomic Hybridisation (aCGH) is preferable to karyotyping as a first test for chromosome analysis because…
- it is better at identifying balanced chromosome translocations
- it is better at identifying polymorphisms
- it has a higher resolution
- it can be used to detect point mutations
- pathogenicity can be assigned to any variant seen
aCGH…
- only detects unbalanced translocations
- will detect more polymorphisms, but not “better” at it, just generates more noise
- does have higher resolution
- cannot be used to identify point mutations
- can’t say that any variants seen cause disease
10 year old girl with severe learning difficulties has a mutation Arg126Try (Arginine to Tryptophan) is identified in the gene that causes Bainbridge Roper Syndrome (ASXL3)
Which would be the strongest piece of evidence that this genetic variant is causing the learning difficulties?
- it is seen at a frequency of 1% in the general population
- it changes the amino acid sequence of the protein
- it is present in the child but neither of the parents who are normal
- it is seen in African but not Caucasian populations
- it is in an important domain of the protein
it is present in the child but neither of the parents who are normal - this is the greatest indicator of a gene being causative
12 year old girl has severe learning difficulties. A deletion of a single base pair is identified in the 3rd exon of the DEAF1 gene (causes learning difficulties). It is not found in either parent.
How would you classify this variant?
- definitely benign
- probably benign
- of uncertain significance
- probably pathogenic
- definitely pathogenic
definitely pathogenic
A couple are expecting a child. The man has a sister that has Cystic Fibrosis. What is the chance that their baby will be born with CF?
Chance of dad being a carrier is 2/3 (know he doesn’t have the condition so isn’t out of 4)
Mother’s chance of being a carrier is 1/25 (population average)
2/3 x 1/25 = 2/75
Child then has a 1/4 chance of actually being affected by the condition
2/75 x 1/4 = 2/300 = 1/150
If someone has Cystic Fibrosis as a result of a G551D mutation, what very specific targeted therapy can they be given?
Ivecaftor - opens up the chloride ion channel which is affected by the G551D mutation
