Autism Ontario Genetics Webinar
Thursday October 29, 2020 12:00 – 1:00 pm Panelist
Stephen Scherer, PhD - Scientist Ny Hoang, MS, CGC – Genetic Counsellor Ryan Yuen, PhD - Scientist Evdokia Anagnostou, MD - Child Neurologist Autism Spectrum Disorders
weak genetic factor Complex Multifactorial Condition strong genetic factor
environmental factors Genetic contribution is highly variable
Strong genetic Moderate genetic Weaker genetic factor factor factor
Examples of genetic factors: SHANK3, NRXN1, CHD8, ARID1B, 16p13.11, 22q11 Genetic contribution is a biological difference
Cell DNA sequence
Protein Genetic contribution is a biological difference
chromosome
Cell DNA sequence
genetic variant
Protein not working Protein Protein not working DNA sequence
genetic variant
Deletions & Duplications Single Nucleotide Variations
1q21.1 deletions/ duplications CHD8, ARID1B, SCN2A, SYNGAP1, 16p13.11 deletions/ duplications SHANK3, ANK2, GRIN2B, CHD2 NRXN3, ASTN2, MBD5, PTCHD1 DNA sequence
genetic variant
Repeat Expansions Example: Fragile X syndrome (FMR1) CGGCGGCGGCGGCGG Normal repeat size: 5-40
CGGCGGCGGCGGCGGCGGCGGCGGCGG Syndrome repeat size: >200 DNA sequence
genetic variant
Repeat Expansions
Fragile X syndrome (FMR1), repeat >200 • Disorders linked to well- CGG defined repeat pattern (motif) Friedreich Ataxia (FXN), repeat >100 • Only one pattern per disorder GAA • Myotonic dystrophy Type 1 (DMPK), repeat >50 Normal repeat size range CTG known Huntington’s Disease (HTT), repeat >35 CAG Spinocerebellar Ataxia Type 10 (ATXN10), repeat >800 A T T C T DNA sequence
genetic variant Important Differences: • Many genes implicated in ASD; not just one gene CDON IGF1 FGF14 MYOCD CACNB1 DMPK New Discovery MBOAT7 FXN
• For any given gene, different repeat patterns uncovered CACNB1:
AAG
AAGAAGGAG
AAGGAGGAG DNA sequence
genetic variant Important Differences: • Many genes implicated in ASD; not just one gene
• For any given gene, different repeat patterns uncovered New Discovery
• Normal repeat size range is unknown
Need to study these repeat patterns in more people with and without ASD