The Molecular Neuropsychiatry and Development Lab focuses on using genetic and molecular biology approaches to identify and characterize genes for autism spectrum disorder (ASD), intellectual disability, Rett syndrome and for bipolar affective disorder.
For Rett syndrome, we discovered an alternative isoform of the gene responsible, MECP2_e1, which we believe is the etiologically relevant form of the MeCP2 protein. Using cytogenetic approaches, we have studied an inversion on 4p in a pair of autistic boys, and identified the neurotransmitter GABA receptor subunit gene GABRG1, which is directly interrupted by the proximal breakpoint. Using microarray data to identify genomic variants that may be involved in ASD, we identified deletions or duplications disrupting a number of genes, in particular the gene PTCHD1 on the X chromosome, and have shown that deletions at or around this gene may be a relatively common cause of ASD. Using consanguineous families from Pakistan, we have discovered the following new genes causing autosomal recessive intellectual disability: CC2D2A, TRAPPC9, TCTN2, MAN1B1, NSUN2.
• Further analysis of PTCHD1 in autistic populations, functional characterization of PTCHD1 protein, development of mouse knockout model for PTCHD1
• Whole exome sequencing in autism trios
• Mapping and identification of genes for intellectual disability in consanguineous families from Pakistan
• Mapping genes for bipolar affective disorder in consanguineous families from Pakistan and Iran
• Mapping genes for bipolar affective disorder in a Canadian population, using association analysis and copy number variation analysis
• Analysis of the MECP2_e1 isoform of the Rett syndrome gene, including screening for mutations individuals with intellectual disability, comparison of gene targets regulated by the MECP2 isoforms, and analysis of mouse models with the specific MECP2 isoforms knocked out.
Dr. Arshad Rafiq, Postdoctoral Fellow
Dr. Kirti Mittal, Postdoctoral Fellow
Taimoor Sheikh, Graduate Student
Dr. Asif Mir, Visiting Scientist
Iltaf Ahmed, Visiting Ph.D. Student
Huda Mahmood, Part Time/Undergraduate Student
Daniel D’Alessandro, Volunteer