SETD1A_mouse_functional_follow_up. SETD1A_mouse_functional_follow_up

The gene SETD1A is a histone methyltransferase a group of genes that have been more broadly implicated in gene regulation in neurodevelopment. We have made a heterozygous knockout mouse line (the homozygote null is not viable), with multiple litters now undergoing behavioral phenotyping to identify whether the mice display a cognitive or behavioral phenotype. We also plan to dissect brain sections from KO and wild type mice after this process to conduct RNAseq (and freeze tissue for possible future ChIPseq) to try to understand what genes are dysregulated by heterozygous KO of Setd1a. While the human genetics result obviously establishes the disease association of this gene more strongly than mouse phenotype, the ability to investigate brain expression and chromatin modelling offers an exciting opportunity to further understand the molecular mechanisms behind this association. Here we propose to sequence whole RNA from six tissues (Hippocampus, Prefrontal cortex, Striatum, Visual cortex Brain stem/cerebellum, Olfactory bulb) from six wild type and six heterozygous KO male mice These 72 libraries will be run on 12 lanes of HiSeq. We will freeze samples for possible future histone methylation ChIPseq, but are not funding that work here. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/