EPIGENOMICS BT-502
EPIGENETICS IN AUTISM SPECTRUM DISORDER
By
Akanksha Singh
M.Tech 1ST Year
00616015322
AUTISM SPECTRUM DISORDER
• Autism is a neurological disfunction disorder
• Characterized by difficulties in social interaction,
communication, restricted and repetitive behavior or
interests.
• Autistic person has shown alterations in brain development
however, exact the mechanism or biosynthesis and causes is
still unknown.
• Over the past 40 years, ASDs have a reported prevalence of
1.47% in the United States , 2.64% in Korea, and 0.25% in
China.
• Therapeutic strategies for most patients with ASDs are
insufficient.
• No clinical test for ASD.
TYPES OF ASD
 Asperger’s syndrome
 Autistic Disorder
 Pervasive Development Disorder, Not otherwise Specified
(PDD-NOS)
 Childhood disintegrative Disorder
 Kanner’s Syndrome
Etiology of ASD
Role of epigenetics in ASD comes from both genetic and environmental risk factors
GENETIC FACTORS
 Not 100% inherited but
chances is there with
environmental factors,
 If there is twin and one of
the twin with ASD then
another one will have 10%
chances of having ASD in
dizygotic twin
ENVIRONMENTAL FACTORS
 Medications or
complication
 Air pollutants
 Viral infection during
pregnancy
 Birth complication
 Gut health during
pregnancy
Epigenetics in ASD
DNA methylation alterations in autism
 DNA methylation analysis of blood cells identified that methylation of HTR4
promoter in children is linked to ASD.
 Study of blood cells reported DNA methylation of the intron1 of OXTR gene in
ASD patients.
 Whole-genome analysis of placental DNA methylome identified alterations in
CYP2E1 and IRS2 genes (decreased and increased, respectively, and confirmed
by pyrosequencing) are associated with autism in later life.
 ASD-associated differentially methylated genes are more likely located on
chromosome X.
 Genes are more likely expressed at postsynaptic membrane and regulate
transcriptions involved in brain development, like in males (e.g., FAM133A,
BRWD3, ITM2A, HMGN5, STS and SHROOM2) and in females (e.g., MAOA,
CUL4B, BCOR, ADGRG4, ELF4 and SLC7A3) and in both (e.g., FMEM47, ZIC3,
KLHL13, AFF2, CPXCR1, FAM155B, GR1A3 and KLHL13).
 DNA methylation alterations associated with autism highly correlate with
affected genes with chromosome 15q duplication and histone-3 lysine 27
acetylation (H3K27AC) regulation.
Folate Metabolism: Combination of genetics, environment and epigenetics
• Dietary folate and vitamin B12 are important components of the Sadenosylmethionine (SAM) synthesis pathway, which is the main donor of methyl
group for DNA and histone methylation.
TABLE 1 : Identified DNA methylation alterations in blood or brain of patients with autism spectrum disorder.
GENE
DNA Methylation status
Tissue
HTR4
Decreased
Blood
SH2B1
Increased
Blood
CYP2E1
Decreased
Placenta
IRS2
Increased
Placenta
CCDC144NL
Increased
Prefrontal cortex
ITGB7
Decreased
Temporal cortex
EYA3
Increased
Cerebellum
OXTR
Decreased
Blood
POTENTIAL THERAPEITIC TARGET
Since DNA methylation is reversible process, it
could be potential therapeutic target for ASD.
Drugs that target DNA methylation, such as
demethylating agents, which may show any
improvement ASD.
CONCLUSION
In conclusion, DNA methylation has been suggested
to play important role in the development of ASD.
Further research is needed to under stand the
complex interplay between genetic and
environmental factors that contribute to the disorder.
However, targeting DNA methylation could be a
promising therapeutic approach for ASD.
References :
Hamid Mostafavi Abdolmaleky , Jin-Rong Zhou and Sam Thiagalingam
Cataloging recent advances in epigenetic alterations in major mental
disorders and autism (2021).
Thank you