Genetics Flashcards
What are single nucleotide variants?
Missense
Nonsense
Splice site alteration
What is a missense mutation?
Amino acid substitution
What is a nonsense mutation?
Generation of a stop codon
What is a splice site alteration?
Defective splicing of the DNA
Resulting from change to donoe or acceptor splice site.
What is an in frame indel?
Insertion or deletion mutation
Results in gain or loss of an amino acid
How many nucleotides must be deleted inorder for there to be an in frame indel?
3,6,9
Must be whole codons deleted
What is an out of frame indel?
Insertion or deletion but not of whole codons
e.g. 2, 5 , 7 nucleotides deleted
What is a frequent issue with out of frame indels?
They often create stop codons.
Protein is detrimentally short
List some benefits of genetic screening of patients
Allows early detection before symptomatic
Prognostic information on course of disease
Allows peace of mind or prevention for couples looking to start a family.
Development of novel focused treatments
Improved understanding of the disease
What are the there primary tumours in Multiple endocrine neoplasia type 1?
Parathyroid
Pancreas
Pituitary
Where else is often affected in MEN1?
Neuroendocrine Thymic Bronchial Gastric Adrenal
What is the gene affected in MEN1?
11q13
Loss or reduced protein function
What is the survival rate of a patient with MEN1?
50%
What is particularly difficult in MEN1?
The mutation can occur anywhere within 11q13 gene.
As a result there is a wide variety of clinical and pathological features can’t be predicted.
Why are the survival rates low in MEN1?
As there is no specific tailored treatment
Treatment is there for individual treatment for pancreatic pituitary tumour etc
What would indicate a need for a genetic screen for MEN1?
Familial link
2 or MEN1 associated tumours
Recurrent parathyroid tumours and hyperparathyroidism
What degree of relation is indicative of a need to do a screen for MEN1?
First degree relative
How is MEN1 passed down?
Autosomal dominant
1 in 30,000
Where is affected in multiple endoplasmic neoplasia type 2?
Parathyroid
Thyroid C cell
Adrenal Chromaffin cells
What gene is affected in MEN2?
10q
RET gene
What kind of gene is RET?
Proto oncogene
A gene which when activated causes cellular division
What is different in MEN2 to MEN1?
The specific RET gene makes clinical features and onset very predictable, also a more targeted therapeutic site.
In MEN2A what are the related tumours?
Medullary Thyroid cancer
Paechromocytoma
Parathyroid
In MEN2B what are the related tumours
Medullary thyroid cancer
Paechromocytoma
+/- Mucosal neurom, intestinal autonomin dysfunction
When do the Medullary thyroid cancers usually develop in MEN2?
Within first few years of life
What is RET?
Tyrosine kinase receptos
Activation triggers oncogenic pathway
