FMRP in Psychiatric Disease

Fragile X Syndrome

Caused by loss of expression of FMR1
FMRP is an RNA-binding protein which stalls target transcript translation at postsynaptic sites in the brain
Found to regulate a broad range of psychiatric disease genes

Symptoms: Elongated face, Broad forehead, low IQ, developmental delays, autism, ADD, seizures

FMRP found to regulate a large number of autism and schizophrenia disease genes

Schizophrenia and Autism disease genes are expressed at different developmental timepoints--do the targets of FMRP change over time?
Can we uncover new disease genes by reanalyzing genetic data w/ an FMRP filter?

8PCW

40 YO

FMR1 expression

Perform CLIP-seq on fetal and adult mice frontal cortex neurons to determine differential regulation by FMRP

Fetal

Old

Sequencing

A) Filter regulated transcripts for disease significance and possible impact

gene list

psychiatric disease genetic studies

B) Test for morphological changes in human neuronal cell lines (KO/overexpression models)

gene list

PGC GWAS, TDT & recurrent DN:LOF w/ SSC

KO gene X