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Autism spectrum disorder is a group of conditions characterized
by:
1) Abnormal social interaction
2) Problems in communication
3) Repetitive and stereotyped behaviors
Clinically ASD are very
heterogeneous
ASD are in large parte genetic conditions but many ASD-genes
are not identified yet
Whole exome and whole genome analysis accelerated
discoveries
The progress of sequencing technology
Sanger sequencing (1977-present)
SFARI gene database
1- How can we study such heterogeneous disorders?
2- How to develop treatments?
3- How acquire confidence in very rare genetic mutations?
How do you treat such a heterogeneous group of disorders?
Is There A Cure For Autism?
Every cell has the same DNA and therefore the same genes.
But different genes need to be “on” and “off” in different types of
cells. Therefore, gene expression must be regulated.
liver
embryo
muscle
bone
sperm
Gene expression must be regulated in
several different dimensions—
In time:
10 wks
6 mos
14 wks
1 day
12 mos
18 mos
At different stages of the life cycle, different genes need to be on and off.
© M. Halfon, 2007
In space:
Paddock S.W. (2001). BioTechniques 30: 756 - 761.
Each colored stripe in this fly embryo shows the expression of a different gene or
set of genes. The spatial regulation of these genes allows the embryo to be
divided up into different regions that will give rise to the head, the internal
organs, the abdomen, etc.
and in abundance:
Clyde et al. (2003). Nature 426:849-853
Note how the gene whose expression is indicated in blue varies in abundance from
strong expression (bold arrow) to weak (thin arrow) within its expression domain.
These differences in strength of gene expression have important functional
consequences.
• Genetic mutations may affect protein expression
• Genetic mutations may affect protein function
Time window of vulnerability
in fetal brain development – thalidomide example
First trimester is also the vulnerable time
for the maternal viral infection risk factor
Rodier, 2000