Genetic approach to autism

Talk by John B. Vincent from Univ of Toronto

Q: Chimeric genes? No.
Q: Expression of the PTCHD1 gene in cerebrum (brain). Parietal, occipital region in human. Ubiquitous expression. Which part of cerebrum is involved in autism? He does not know.
Q: How PTCHD1-disrupted mice are evaluated for autism? Communication.

PTCHD1 locus in autism and intellectual disability

Autism (ASD)
Focus on X: Males are nearly 4 times as likely to be affected by autism as females.
Skewed X-inactivation in autism

PTCHD1
Located at Xp22.11
Predicted Hedgehog receptor activiry

rf: Dhh, Shh, Ihh are hedgehog ligands that tranduces signaling to Gli transcription factor.

Intragenenic deletion

PTCHD1V195I + de novo DPYD (pyrimidine metabolism) deletion

Prevalence: 0.8 to 5.6 in 10,000
Broader spectrum includes Asperger syndrome.
3% risk to siblings
60% concordance for MZ twins; 92% MZ concordance for broader spectrum vs 10% for DZ twins.

t(7;13) translocation in the patient with autism
t(5;7)(q15;q31.32)

CNV
FoxP2 deleted

SNP microarray analysis

Postsynaptic density genes
Synaptic comlex genes: PCDH9, PTCD1

Knockout of PTCHD1 in mice

Method: Linkage analysis

Mendelian genetic trait (Simple)
Cystic fibrosis (recessive) Huntington (dominant)

Non-mendelian traits (complex)
Polygenic diseases: asthma, cancer, schizophrenia, bipolar affective disorder- many genes of smallish effect (plus environment)