Next-gen sequencing identifies non-coding variation disrupting miRNA-binding sites in neurological disorders

• DOI: 10.1038/mp.2017.30
• Publication Date: 2017-03-14T09:04:10Z
• Authors: P Devanna; X S Chen; J Ho; D Gajewski; S D Smith; A Gialluisi; C Francks; S E Fisher; D F Newbury; S C Vernes
• Keywords: Neurodevelopmental disorder

Understanding the genetic factors underlying neurodevelopmental and neuropsychiatric disorders is a major challenge given their prevalence potential severity for quality of life. While large-scale genomic screens have made advances in this area, many underpinnings are complex poorly understood. To date field has focused predominantly on protein coding variation, but importance tightly controlled gene expression normal brain development disorder, variation that affects non-coding regulatory regions genome likely to play an important role these phenotypes. Herein we show 3 prime untranslated region (3'UTR) variants across disorders. We devised pipeline identifying functionally validating putatively pathogenic from next generation sequencing (NGS) data. applied cohort children with severe specific language impairment (SLI) identified functional, SLI-associated variant affecting regulation cells post-mortem human brain. This affected (ARHGEF39) represent new putative risk SLI. Furthermore, 3′UTR autism, schizophrenia bipolar disorder NGS cohorts demonstrating impact Our findings investigating when determining contributing In future, integration such changes will be essential uncovering causes neurological fundamental mechanisms health disease.