genetics formative Flashcards
there is a single base mutation of a ‘C’ to a ‘T’ in the 3rd exon of the ASXL3 gene.
What is the most likely reason that this has NO effect on protein sequence ?
codon usage shows redundancy
a base change in an exon will lead to a messenger RNA with a different sequence
what is meant by codon redundancy?
where different codons can encode the same amino acid
so your RNA sequence can change + cause no effect on protein sequence of amino acids
A 12 year old girl has severe learning difficulties. A deletion of a single base is identified in the 3rd exon of the DEAF1 gene (A gene that causes learning difficulties). This is not found in either parent.
How would you classify this genetic variant ?
definitely pathogenic
this gene causes a developmental disorder
deleting a single base pair in an exon causes a frameshift at translation - almost always destroying a protein
it is denovo
Where would you plot the common FGFR2 gene variant rs2981382 that causes a 1.2 fold increase in breast cancer risk ?
E
small effect = low penetrance, in a common disease that is prevalent in the population
Next generation sequencing of genes has an advantage over sanger (conventional) sequencing because
It allows sequencing of a much larger number of genes
- can do whole exome or whole genome
- allows sequence a lot of genes cheaply - more expensive than doing a single gene traditionally
- will throw up lots of polymorphisms (disadvantage)
Which ethical principle is most important in genetic counselling for your patient when she asks for a genetic test ?
patient autonomy
A 20 year old man has Neurofibromatosis type 1 (NF1). A base change altering an amino acid (Arginine to Histidine) in the NF1 is identified. It is also seen in 5% of the general population.
How would you classify this genetic variant ?
definitely benign
it is found in 1 in 20 people + only 1 in 3000 have NF1
What is the first step in the ‘Central Dogma’ of making a protein from a gene?
trancription
in nucleus -
- DNA to mRNA. Transcription
- mRNA to mature mRNA – splicing out of introns leaving just exons
In the cytoplasm /at the ribosome
- Translation – mRNA encodes protein(3 bases =1 amino acid)
- Post translational modification – folding and moving your polypeptide to make it a useful protein
Array Comparative Genomic Hybridisation (aCGH) is preferable to karyotyping as a first test for chromosome analysis because:
it is higher resolution
- it can resolve down to very small imbalances (missing or extra genetic material)
- It doesn’t detect balanced variation (no extra or missing material)
- it is not widely used for mutation detection.
WRONG ANSWERS
- better at identifying balanced chromosome translocations
- better at identifying polymorphisms
- can be used to identify point mutations
- pathogenicity can be assigned to any variant seen
What characteristic of a cancer cell is central to allowing it to acquire further new characteristics ?
genomic instability
other answers are true but not correct to question -
- loss of contact inhibition
- escape from immune surveillance
- somatic mutations that promote metastasis
A 10 year old girl has severe learning difficulties. 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 present in the child but not both normal parents
missense variation - changes amino acid sequence
“de-novo in the right gene” **
one of the strongest filters for sequence in developmental disorders
de-novo in the right gene
Most people have around 120 de-novo variations (not in their parents)
- If one falls in a gene that causes a developmental disorder, then the child will be affected.
- 40% of severe developmental disorders in children are caused by this.
A 64 year old man is affected with hypertrophic cardiomyopathy, and has a Ile345X (stop) mutation in the MYBPC3 gene. His 32 year old son is healthy and has a normal heart scan, but is shown to carry the same mutation.
What is the most likely genetic explanation for the normal scan in his son ?
the mutation has variable prenetrance
Mrs White comes to see you, she has a boy with Down syndrome and is currently 18 weeks pregnant.
What is the risk that this new child will also have down syndrome ?
Approximately 1% if child has primary trisomy 21
o Higher if caused by Robertsonian translocation
(most cases of Down syndrome are not inherited, but occur as random events during the formation of reproductive cells)
chromosome changes that indicate treatment in cancer
her22 amplification
-> monoclonal antibody = trastuzamab
philadelphia chromosome
-> tyrosine kinase inhibitor
