Autism spectrum disorder (ASD) and microcephaly

Question 1

Describe the behavioral characteristics of ASD.

Answer 1

Impaired social communication

Restricted interests

Stereotyped/repetitive behaviors

Question 2

What is the difference in the modes of genetic effects between common genetic variants and rare genetic variants?

Answer 2

Common risk alleles have to accumulate (genetic burden) in order to develop the disease.

Rare deleterious alleles have monogenic effect and larger impact.

Question 3

What is the rationale that synaptic plasticity is impaired in ASD?

Answer 3

Generated genetic models of ASD (mouse - PTEN) and noticed impaired synaptic plasticity.

Question 4

Describe a possible study design of analyzing the molecular between normal and ASD patients.

Answer 4

CLINVAR - database of genomic variation in disease

Question 5

What are brain ventricles?

Answer 5

Empty space with fluid to help protect brain from shock.

Question 6

What are the 2 pathophysiological mechanisms leading to microcephaly, and give an example of each.

Answer 6

Insufficient neural stem cell proliferation - mutation in ASPM. Decreases radial glial cells.

Abnormal apoptosis of neural stem cells - Zika attacks radial glial cells.

Question 7

What is the limitation of the mouse as a model organism in neurodevelopmental disease, and which other animal model can be proposed?

Answer 7

Humans have radial glial cells, while mice do not. Ferrets are the proposed model.