PSYC20006 Lecture Notes - Lecture 14: Bipolar Disorder, Fmr1, Synaptic Plasticity
12 Jun 2018
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Lecture 14 - Thursday 13 April 2017
PSYC20006 - BIOLOGICAL PSYCHOLOGY
LECTURE 14
BEHAVIOURAL & PSYCHIATRIC GENES
KARYOTYPE
•This male has fragile X syndrome. On average
they will have very low IQs (40 on average).
•The bottom of the X chromosome coincides
with the gene that encodes the protein for the
syndrome, the FMR1 gene. It has a role in lots
of parts of the body, critically in the brain, in
synaptic plasticity. Synapses rely on this gene
and the protein it produces.
•They have up to 1000 repeats of this base
sequence. We usually have about 20-40.
•It is a monogentic disorder; can be traced
back to a single gene. This is the exception,
not the rule of understanding cognition.
•There is no gene for schizophrenia/
depression/bipolar disorder the way there is
for fragile X syndrome; they are polygenic
disorders.
TODAY
•Molecular genetics of psychological disorder
•Many genes, small effects
•Megastudies & metastudies
•Endophenotypes
MOLECULAR GENETICS OF
PSYCHOLOGICAL DISORDER
•About a dozen years ago, micro-rays were adapted
for use in studies. We can measure the genotype.
•Each point is highly correlated with it’s neighbours;
if we have enough info, we can predict most of
what’s there; don’t need to specifically look at all of
it.
•This technology is effective to identify genetic
variants causing things.
•Chromosomes associated with diseases, cancer,
drug response etc. The genome wide association
was very effective for these diseases, but not so
much for psychological disorders.
•Group of 50 research organisations in the UK !
Lecture 14 - Thursday 13 April 2017
PSYC20006 - BIOLOGICAL PSYCHOLOGY
!
pooled their resources
to do a study of 7
diseases.
•Controls =
unaffected
individuals.
•Key results in blue.
This type of data
representation is
called a Manhattan
plot.
•The higher the point
on the horizontal
axis.
•Height of point on y
axis = higher = more
effect, higher p value,
higher association
between variant and
disease we are looking
at.
•Bipolar disorder, the only psychological disorder in it,
didn’t give much info at all (neither did hypertension
really).
•A year later there was a new study, using 10k people.
Combining old studies and new.
•Relatively robust association with gene ANK3. Should
be chromosome 12 position not chromosome 10.
•Calcium channel responsible for the whole action
potential synaptic gap shit.
•Also voltage gated Na+ channels.
•Both of these genes are down-regulated by !
Document Summary
On average they will have very low iqs (40 on average): the bottom of the x chromosome coincides with the gene that encodes the protein for the syndrome, the fmr1 gene. It has a role in lots of parts of the body, critically in the brain, in synaptic plasticity. Synapses rely on this gene and the protein it produces: they have up to 1000 repeats of this base sequence. We usually have about 20-40: it is a monogentic disorder; can be traced back to a single gene. This is the exception, not the rule of understanding cognition: there is no gene for schizophrenia/ depression/bipolar disorder the way there is for fragile x syndrome; they are polygenic. Today: molecular genetics of psychological disorder, many genes, small effects, megastudies & metastudies, endophenotypes. Psychological disorder: about a dozen years ago, micro-rays were adapted for use in studies.
