0:00
My
name is Rohan de Silva,
and I'm from the UCL
Institute of Neurology
at University College London.
And today, my lecture will
focus on the genetics of two
sporadic Parkinsonian disorders--
Progressive Supranuclear Palsy
and Corticobasal Degeneration, also
known by the acronyms PSP and CBD.
0:20
Although these disorders are very
rare, they are primary tauopathies.
That is, they are caused
by tau protein dysfunction.
And I will come back to this later.
And they're therefore good models
for the study of the central role
of the tau protein
in neurodegeneration.
And although they are sporadic
disorders without any inherited
gene defects, it is clear
from genetic association
that common polymorphism
in the tau gene
is a significant risk
factor for PSP and CBD.
As a result, PSP in particular
has been a good example
for illustrating the
possible functional basis
of such genetic
associations, and these
go beyond the missense
changes that affect
the coding sequences of genes.
More recently, additional
genetic factors
were identified in a genome-wide
association study that implicates
cellular processes other than tau.
And I will describe these in
the last part of this lecture.
1:17
From a genetic point of view,
we have the inherited Mendelian
disorders that are relatively rare.
But in most cases, a coding
mutation is inherited from parents
to offspring in an autosomal
dominant or recessive fashion.
These Mendelian mutations
confer higher risk.
They're depending on penetrance, or
the severity of the coding change,
due to the inherited mutation or
due to interaction with other genes.
The carrier of the
mutated gene is more
or less certain of
inheriting the disorder.
