Genotype-Phenotype interactions - how factors can influence the phenotype of a certain genotype:

factors include:

Mutation Type
What type of mutation is it? e.g. missense, nonsense, does it cause a frameshift?
EXAMPLE - DMD and BMD - same gene, one mutation causes frameshift, one doesn't

Mutation Location
Mutations can affect the protein product differently according to their location. At one position they may render the protein non-functional (null mutation), whereas others may reduce the activity of the protein (loss of function).
EXAMPLE -Haemoglobinopathy - genetic defect leading to alteration in the structure of haemoglobin - e.g. sickle cell disease
Of the mutations in the haemoglobin gene:

One mutation (missense mutation at 6th aa position) leads to sickle cell anaemia
Others can lead to thalassaemia (weakening and destruction of red blood cells)
Others can lead to polycythaemia - a benign condition that can cause a 50% increase in the oxygen carrying capacity of the blood. This can be beneficial to athletes, giving them advantage in endurance events.

Genetic Background
Common variants (polymorphisms) can form an additive risk/protective factor for certain conditions and thus this interacts with the effect of the mutant allele.
EXAMPLE - Sick Sinus Syndrome - arrhythmias caused by malfunction of the sinus node

SSS is caused by a mutation in the gene SCN5A
A common SNP in this gene H558R has been shown to modulate the effect of the mutation
Gui et al 2010 found that 558R was able to rescue some of the loss of function defect in certain mutant ion channels.

X-inactivation
Skewed x-inactivation can occur - for example, phenotype of x-linked disorder may be expressed in a female
Adrenoleukodystrophy - female may show earlier onset of neurological symptoms/more severe

Genomic Imprinting
See epigenetics - Prader-Willi vs Angelman Syndrome

Environment
e.g. lifestyle, diet, stress

	Created by Ellie Quinn about 10 years ago

Note on Genotype-Phenotype Interactions, created by Ellie Quinn on 12/02/2014.

Genotype-Phenotype Interactions