Ansa Zakriya

IRI/3/10h
May 6 2020

Data Collection

Wall, D. P., et al. “Comparative Analysis of Neurological Disorders Focuses Genome-Wide

Search for Autism Genes.” ​Genomics​, vol. 93, no. 2, Feb. 2009, pp. 120–29,
doi:10.1016/j.ygeno.2008.09.015.

Why I chose this article: It shows which disorder are closely related to Autism, which then
provides possible causes of ASD.

Summary: This study grouped disorders into categories. Those closely related to Autism were
studied in detail; genes related to these disorders were marked to see if they were related to
autism. Following the gene mapping, the researchers looked to see if the genes that were found
corresponded with any biological processes which could then cause a disorder such as autism.

Kang, Eunchai, et al. “Interplay between a Mental Disorder Risk Gene and Developmental
Polarity Switch of GABA Action Leads to Excitation-Inhibition Imbalance.” ​Cell Reports​,
vol. 28, no. 6, Aug. 2019, pp. 1419-1428.e3, doi:10.1016/j.celrep.2019.07.024.

Why I chose this article: The main focus in my paper is GABA and this study proves the
importance of GABA in the maturing brain.

Summary: This study revealed the homeostatic mechanisms of the brain through glutamate and
GABA. These mechanisms are crucial during neuronal development. Additionally a switch in
GABAs properties were found from depolarizing cells to hyperpolarizing cells.

Chen, Chia-Hsiang, et al. "Genetic analysis of GABRB3 as a candidate gene of autism spectrum
disorders." ​Molecular Autism,​ vol. 5, no. 1, 2014. ​Gale Academic OneFile Select​,
https://link.gale.com/apps/doc/A541245908/GPS?u=clar33415&sid=GPS&xid=9dc628f.

Why I chose this article: GABA is the focus of my paper and it shows the connection between
Autism and the major excitatory neurotransmitter, GABA.

Summary: Overall this study was mainly to just find any correlation between the GABRB3 gene,
which encodes GABA beta 3 receptor. In addition the article explains in less detail about other
GABA subunits such as alpha and gamma.
 Article 1 Article 2 Article 3

Purpose of the study To find correlating To see the effects of To find an association
disorder that can the imbalance of between the
show genes that may excitatory and GABRB3 gene and
relate to Autism inhibitory responses autism

methods - 433 - All - All subjects

neurological experiments are chinese
disorders from were done on from Taiwan
National both male and - Total of 356
Institute of female mice patients
Neurological - Engineered - Mean age
Disorders and murine 8.84
Strokes oncoretrovirus - 386 control
- Seed lists es were used subjects
were provided to birth, date, - Genomic
by OMIM and and label DNA was
GeneCards proliferating taken from
cells and to peripheral
coexpress blood cells
shRNAs

results - 14 biological - Changes in - Six known

processes glutamatergic common
were found and SNPs were
GABAergic identified in
that were
synaptic this study
linked to these transmission - - Altered
genes in mutant GABRB3
(uncorrected) neurons gene
- Establishment shows an E-I expression
of imbalance may be
localization, involved in
the
localization, neurobiology
nervous of ASD
system
development,
cell
organization
and
biogenesis,
 locomotion,
localization of
cell, cell
motility,
cytoskeleton
organization
and
biogenesis,
cell
communicatio
n, ell
differentiation
, cell-cell
signaling,
transport.

other - Tested 334 - Looked at the Mice with the

genes directly effects of deletion of GABRA5
correlated to DISC 1 had increased
deficiency on
one of the learning and memory,
synaptic
MDAG and properties of whereas the deletion
found that 31 GFP granule of GABRB3 had
were neurons in the epilepsy and
regulated dentate gyrus behavioral
differently in after 28 days abnormalities and
autism Result: lower density learning deficits and
compared to of the retrovirus memory problems
the control being injected critic and more
spine density

In these mutant
neurons the density of
mature mushroom
spines reduced,
suggesting deficits in
the formation or
maintenance of
glutamatergic
synapses
 Mean frequency of
GABAergic SSCs
increased in the
mutant neurons

Changes in synaptic
transmissions
suggests an E-I
imbalance

other - 66 multi - Synaptic - Two genetic

disorder properties markers in the
autism gene examined 14 GABRB3
days after
set (MDAG) gene
injection:
were found in GFP+ neurons associated
autism and in showed with autism
at least one of increased
the autism frequencies of
sibling both GABA
disorders and glutamate
SSCs in
mutant
neurons

Result: DISC 1
deficiency leads to
more GABA synaptic
formation but less
glutamate

other - Created a Depolarizing PV+ - There are

phylogeny synaptic inputs onto three missense
that grouped immature neurons are mutations
needed for which might
autism with
GABAegeric and have a
13 related glutamatergic functional
disorders synapse formation impact on
GABRB3
 - Asperger Results: PV+
syndrome, promotes GABA and
angelman glutamate synapse
formation and drives
syndrome, rett
precocious synapse
syndrome, formation with DISC
hypotonia, 1 deficiency
infantile
hypotonia,
spasticity,
microcephaly,
mental
retardation,
fragile x,
ataxia,
hypoxia,
seizure
disorder,
tuberous
sclerosis

conclusion - This article - In mutant - Overall this

provided the neurons the study is not
most glutamatergic clear enough
information, and on its own to
however this GABAergic be used,
information is pathways do however
the least not balance many of its
specific but it out which findings such
can be used to leads to ASD as possible
mend ideas mutations in
together GABRB3
may lead to
ASD
 Analysis

The first article provided the most broad information but overall in my research paper this will be

the most useful as I have been trying to simplify my information. The genes provided in the

study show connections to other disorder therefore ASD may be a combination of these

disorders. According to the information provided the most common genes that correlate with

autism are linked to cell migration, cell signaling, nervous system development, and cell

differentiation. In essence these processes that are damaged negatively impact the development

of the brain, thus proving these genes may have a relation to ASD as it is a mental disorder.

Corresponding to these genes the third article provided specific information on one gene,

GABRB3 and specific SNPs that cause the mutation. This article is the bridge from the gene

analysis article to the E-I imbalance article as it relates to the gene article because it explains in

detail GABRB3; additionally, it related to the homeostatic article as it introduces GABA. The

excitation inhibition article proves the significance of early brain development and how

mutations related to these homeostatic mechanisms cause Autism like symptoms.