The document discusses an experiment testing the effect of knocking down the C. elegans homolog of the human SynGAP gene, called gap-2, on short-term memory in worms. Worms that had gap-2 knocked down using RNAi showed impaired ability to retain short-term memory compared to control worms. This provides a model for how mutations in the human SynGAP gene could cause memory impairment and suggests gap-2 is important for short-term memory in worms.

1. Early-onset rasgap-2 mutations impair short-term memory retention in C. elegans
Vienna Kuhn ‘16
A Biology 600/610 Project
Abstract
SynGAP, a newly identified rare neurological
disease, is one of many new diseases that have been
identified thanks to genomic sequencing of
undiagnosed disease cases. With the disease’s
many ties to autism and epilepsy, the mutation in
the SYNGAP1 gene could be more prevalent than
previously expected. The mutation, like many
others that cause intellectual disability, affects
neurons and their synaptic transmissions. The exact
connection of this mutation to the symptoms of
intellectual disability, such as short-term memory
impairment, are as of yet unknown, but a homolog
to the SynGAP gene that has been identified in C.
elegans may provide some clues. An experiment
testing worms that have had the gene eliminated
will seek to confirm whether these worms have
impaired short-term memory in comparison to
worms that have a functioning copy of the gene.
This information might be extrapolated to how the
gene mutation in humans may be, on a molecular
level, responsible for the physical and mental
symptoms that manifest themselves in patients.
Conclusions:
Gap-2, the homolog of the SynGAP gene in
humans, impairs the worm’s ability to retain
short-term memory when it is knocked down
using RNAi. This can be extrapolated to human
subjects and provides a useful model for future
research on memory impairment in C. elegans.
Implications for the Future:
The more that is known about the human gene
and its homologs in other organisms, the more
likely it is that similar diseases can be identified,
locating possible treatments for the amelioration
of existing symptoms and hopefully an eventual
cure.
OP50-fed Memory Assay Results (control)
Rare Disease Facts
Graph of results of RNAi on memory
(from outside experiment)
The process of RNAi interference
RNAi-fed Memory Assay Results
Worms in
Attractant
Region
Worms Not in
Either Region
Worms in
Counter-
Attractant
Region
Total
81 161 50 292
Worms in
Attractant
Region
Worms Not in
Either Region
Worms in
Counter-
Attractant
Region
Total
411 indeterminate 173 Unknown
Worms were counted within a 2x1 cm rectangle around point where attractant and
counter-attractant were added to the plate. Many worms did not move from their
point of origin.
Worms were counted within a 2x1 cm rectangle around point where
attractant and counter-attractant were added to the plate. Again, many
worms did not move from their point of origin. Based on the density of
worms, I surmised there were upwards of 1000 on the test plate.
Comparison of worm counts in regions of attractant
and counter-spot for different feeding groups of
worms
“Negative conditioning assays were combined with RNA interference experiments
using eri-1(mg366);lin-15B(n744) RNA sensitized worms, fed against (A) gap-1 (n=
3), (B) gap-2 (n = 13, p = 2.72 × 10 −7
), and (C) gap-3 (n=9, p=3.75×10 −5
) dsRNA
carrying bacteria. Dark grey represents the same strain fed with bacteria carrying an
empty GFP marker dsRNA as reference. N: naïve, C: conditioned, R: recovered animals
(see Materials and Methods for details). Error bars indicate SD and asterisks indicate
significant differences (***P<0.001).”
From: http://dx.doi.org/10.1038/srep15084
The process is co-opted using non-native RNA to begin the response.
From: http://www.alnylam.com/rnai_primer/rna-interference-pg5.htm
1. There are 7000 different types of rare
diseases and disorders in the world, and
counting
2. Only 5% of these have even one FDA-
approved drug treatment
3. Collectively, these diseases affect over 350
million individuals
4. 80% are genetic in origin
From: Global Genes
https://globalgenes.org/rare-diseases-facts-statistics/