Autism is a neurodevelopmental disorder characterized by difficulties with social interaction and communication. It has a strong genetic component, with heritability estimates ranging from 40-80%. While hundreds of genes have been implicated, no single gene accounts for more than 1-3% of cases. Both rare and common genetic variants, as well as environmental factors, contribute to autism risk. The causes are highly heterogeneous and complex. Understanding the underlying genetics may help lead to improved diagnosis, treatment and prevention.

1. Autism genetics
1
By : Mostafa Davoodabadi Farahani
Under supervision of : Dr. M. Entezam

2. What is autism?
Autism Spectrum Disorder (ASD) comprises a wide range of neuro-
developmental disorders characterized by difficulties with social
communication and interaction
Onset in childhood; continues into adulthood
2

3. Symptoms
It has a number of symptoms including cognitive, behavioral, and sensory
symptoms
Sleeping and eating difficulties, synesthesia as well as dysregulation and
difficulty with initiation, planning and organization of task
Impairments in social interaction
Impairments in communication
3

4. Rising Prevalence of ASD
 6-7/ 1,000 children (0.6%–0.7%).
 2.6% among children in areas of Asia, Europe, and North
America
 4-5 boys are affected for every girl
4

5. Heritability
Heritability 40% to 80%
Identical twins shared 60% to 90% of autistic traits compared to
fraternal twins who only shared 0% to 10%
Sibling recurrence as high as 19%
5

6. Etiology
Most cases involve a complex and variable combination of
 Genetic risk and environmental factors that influence early brain
development
It is estimated that rare genetic variants, both de novo and
inherited, are causal in 10–30% of people with ASDs
6

7. Perceptions of Causes
The perceived causes reported most commonly by parents of
autistic children include
Genetic influences
Pregnancy and/or delivery problems
Childhood illness
Vaccines to child or pregnant mother
Diet
Environmental exposure
7

8. 8

9. Why so hard to find the genetic answer
More than 800 genes
Highly heterogeneous disorder
Variable penetrance
Genetic pleiotropy
Until very recently, limited ability to search through the genome
9

10. Cont…
Often not due to single gene ….not a 1 to 1 relationship between
genetic risk and outcome
Father’s age linked to risk for autism and schizophrenia
Yuen and colleagues published a new study….
one-third of siblings with autism shared similar genetic variations, which
was inherited from one of their parents
10

11. Different approaches in genetic analysis
Structural gains and losses of genetic materials at
submicroscopic resolution(CNV)
Single nucleotide polymorphisms(SNP)
 Common and rare variations mutations contribute to ASD
risk
11

12. Copy number variants
Structural gains and losses of genetic materials called
Cytogenetic studies help detection of chromosomal abnormalities
to locate relevant genes for autism
Large de novo CNV (~500 kbp) account for about 6-10% of ASD
12

13. Cont…
A number of duplications, deletions, and insertions have been
reported in autistic children
maternal duplication 15q11-13, which accounts for ~ 1-3% of autism
microdeletion of 16p11.2 which accounts for ~ 0.5% of autistic
patients
13

14. 14

15. 15

16. SNP
Effectively identifying common risk variants using the GWAS
approach will require tens of thousands of samples
The results of the ASD GWASs, which so far have been inconclusive,
suggest that there is no single common variant with a substantial
effect on the risk of ASD
16

17. 17

18. Immune-related genes
In autism, several HLA alleles located in class I, class II, and class III
regions, were found to be implicated in the pathogenesis of autism
Autistic children exhibited a significantly higher frequency of
HLADRB1*11 allele, and a significantly lower frequency of HLA-
DRB1*03 allele compared to the controls
18

19. CON…
14- bp insertion polymorphism HLA-G gene autism
development prenatal immune activation.
 The supporting the notion that prenatal immune activation plays an
important role in autism development
19

20. Important genes
Some of candidate genes play different roles in the pathogenesis of
autism, by affecting brain structure and function
 mediating different behavioral responses
 impairing learning and memory process
 impairing motor and cognitive development
 impairing speech and language process
 affecting social behaviors.
20

21. 21

22. 22

23. 23

24. Associated syndromes and medical
conditions
Individuals with the following conditions account for 5-10 % of cases of ASD
 Sex chromosome trisomies , XYY and Klinefelter syndrome(XXY)
Fragile X, Rett
 Tuberous Sclerosis
Smith-Magentis
 Angel man, Parder-Willi
DiGeorg(22q11.q) 24

25. Environmental Epigenetics
 Histone methylation is different in persons with ASD compared to controls on
genes regulating neuronal connectivity, social behaviors, and cognition
 Epigenetic changes from methylation related to environmental exposure
during pregnancy might increase the risk of ASD
25

26. Genetic testing
26

27. Conclusion
Understanding the etiology of ASD may help in development of
biomarkers for its prediction, diagnosis, prognosis, and eventually in its
prevention
elucidating the Genes associated with autism and the effect of their
products on brain
Genetic counseling
earlier treatments for children with a genetic predisposition towards
autism. 27

28. Refrences
• Autism genetics: opportunities andchallenges for clinical translation. Jacob A. S.
Vorstman1, Jeremy R. Parr2, Daniel Moreno De Luca3, Richard J. L.‑ ‑
Anney4,John I. Nurnberger Jr5,6 and Joachim F. Hallmaye. 2017 Macmillan
Publishers Limited, part of Springer Nature
• Genetic Markers Association in Autism Spectrum Disorder .Nadra E Elamin1*
and Laila Y AL-Ayadhi1. Elamin and Al-Ayadhi, J Clin Med Genomics 2015, 3:2
28

29. Thank you
29