Thread by @ksamocha

Graham Erwin (@grahamserwin) #ASHG22: Half of the human genome is repetitive, most are transposons but about 3% is made up of tandem repeats. Tandem repeats cause >40 human diseases.

Graham Erwin (@grahamserwin) #ASHG22: Friedreich's ataxia is caused by a triplet expansion in the first intron of FXN gene. Patients have 70++ repeats, which leads to lower expression/protein levels.

Graham Erwin (@grahamserwin) #ASHG22: Polyamides bind to DNA specifically and are very small (cell permeable). Prior example to tie one of these to a factor that would lead to higher transcription.
pubmed.ncbi.nlm.nih.gov/29192133/

Now want to target other repeats.

Graham Erwin (@grahamserwin) #ASHG22: Most of the tandem repeats are >150 repeats. But with short read sequencing, it is hard to map these repetitive regions.

Graham Erwin (@grahamserwin) #ASHG22: ExpansionHunter De Novo detects repeat expansions from short read data. Modified the code a bit to find 160 recurrent repeat expansions identified across 7 cancer types.

Preprint:
biorxiv.org/content/10.110…

Graham Erwin (@grahamserwin) #ASHG22: Does the rate of microsatellite instability correlate with recurrent repeat expansions?

Nope.

Graham Erwin (@grahamserwin) #ASHG22: Have several examples of recurrent repeat expansions in the cancer types that they want to dig into in the future.