Gene expression and splicing profiles across models of TTDN1 deficiency

The molecular networks disrupted in Non-photosensitive trichothiodystrophy (NP-TTD) are largely uncharacterized. NP-TTD is linked to mutations in the gene encoding TTDN1, an uncharacterized protein thought to have functions in splicing or trasncription . The goals of this study are to identify splicing and gene expression defects occuring in multiple models of TTDN1 deficiency, including U2OS and Hela-S cell lines, as well as in cortical tissue from TTDN1 deficient mice. Overall design: mRNA profiles from WT and TTDN1 -/- U2OS and HeLa-S cell lines, as well as from 8 week old wild-type (WT) and knockout (KO) mice were generated by deep sequencing, in triplicate (cell lines) or in quintuplicate (mice), using Illumina Novaseq 6000 2x150bp. The sequence reads that passed quality filters were used to determine differential gene expression, gene length, splicing differences, and lariat identification between KO and WT samples.