Mental health 1

Question 1

What is a GWAS?

Answer 1

Genome-wide association study

genome wide study looking at genetic variants and trying to see if any variant is associated with a particular trait

Question 2

How were genetic risk factors identified prior to GWAS’?

Answer 2

Genome analysis of inbred families- where mental health conditions were common

Question 3

What is DISC1?

Answer 3

Mutant gene is a genetic risk factor for mental illness

Identified through the genetic analysis of an inbred family

Question 4

How is schizophrenia usually triggered?

Answer 4

Environmental and social triggers-

stress, lack of sleep, substance abuse

Question 5

Why is it hard to study mental health conditions? And what is important to do when we do study it?

Answer 5

Likely that there are multiple variables - a consequence of genes and the environment
Important to use high numbers (zebrafish and drosophila good in this respect) - in order to produce robust conclusions

Question 6

Where is DISC1 expressed in the zebrafish embryo?

Answer 6

In the hypothalamus

Specifically in hypothalamic stem/progenitor cells

Question 7

What is the HPA axis?

Answer 7

Hypothalamus - CRH
Anterior pituitary gland- ACTH
Adrenal cortex - CORTISOL

Question 8

What were the 2 point mutations induced in disc1 mutant zebrafish? And what occurred

Answer 8

LL15
Y472
No full length DISC1 protein or mrna was produced

Question 9

What do we think is occurring in terms of hypothalamic progenitors in disc1 mutants?

Answer 9

We think theyre differentiating early

The progenitor cells differentiate early and thus there are none left for differentiation later in life

Question 10

What is the significance of the ventricular zone in the developing nervous system?

Answer 10

Harbours progenitor cells set aside for later differentiation
The progenitors go through waves of differentiation

Question 11

How are pomc, sf1, and CRH neurons effected in disc1 mutants?

Answer 11

Few pomc neurons

Too many sf1 and CRH neurons

Question 12

How can you measure stress responsed in adult fish?

Answer 12

Behavioural assays- exposure to salt water, the skin of other fish
Neuroendocrine analysisn- upregulation of neurohormones after stress, upregulation of cortisol after stress

Question 13

What is upregulated in wild type and disc1 mutant alarmed fish?

Answer 13

WT- cortisol and s1f1 is upregulated

no chance in disc1 mutants