FMR1 gene full-length long read sequencing

The FMR1 gene, as many housekeeping genes, undergoes alternative splicing. Using Single Molecule, Real-Time (SMRT) sequencing and qRT-PCR we have recently reported that the relative abundance of all FMR1 mRNA isoforms is significantly increased in the premutation group compared to controls. However, there is a disproportionate increase, relative to the overall increase in mRNA, in the abundance of isoforms spliced at both exons 12 and 14. In this study, we have further investigated the transcriptional FMR1 isoforms distribution pattern in different tissues including muscle, brain, heart and testes from 3 individuals with a premutation allele and affected by Fragile X-associated tremor/ataxia syndrome (FXTAS) and compared them to the isoform mRNA profile of age-matched controls. Here we report on the identification of novel isoforms which might play a role in the pathogenesis of FXTAS.