Candidate variants in TUB are associated with familial tremor.
M Reza SailaniFereshteh JahanbaniCharles W AbbottHayan LeeAmin ZiaShannon RegoJuliane WinkelmannFranziska HopfnerTahir N KhanNicholas KatsanisStefanie H MüllerDaniela BergKatherine M LymanChristian MychajliwGünther DeuschlJonathan A BernsteinGregor KuhlenbäumerMichael Paul SnyderPublished in: PLoS genetics (2020)
Essential tremor (ET) is the most common adult-onset movement disorder. In the present study, we performed whole exome sequencing of a large ET-affected family (10 affected and 6 un-affected family members) and identified a TUB p.V431I variant (rs75594955) segregating in a manner consistent with autosomal-dominant inheritance. Subsequent targeted re-sequencing of TUB in 820 unrelated individuals with sporadic ET and 630 controls revealed significant enrichment of rare nonsynonymous TUB variants (e.g. rs75594955: p.V431I, rs1241709665: p.Ile20Phe, rs55648406: p.Arg49Gln) in the ET cohort (SKAT-O test p-value = 6.20e-08). TUB encodes a transcription factor predominantly expressed in neuronal cells and has been previously implicated in obesity. ChIP-seq analyses of the TUB transcription factor across different regions of the mouse brain revealed that TUB regulates the pathways responsible for neurotransmitter production as well thyroid hormone signaling. Together, these results support the association of rare variants in TUB with ET.
Keyphrases
- transcription factor
- single cell
- copy number
- deep brain stimulation
- metabolic syndrome
- induced apoptosis
- parkinson disease
- insulin resistance
- mitochondrial dna
- genome wide
- physical activity
- gene expression
- early onset
- dna methylation
- body mass index
- late onset
- cancer therapy
- drug delivery
- weight gain
- cell cycle arrest
- adipose tissue
- cell death
- dna binding
- cord blood
- signaling pathway