Bioinformatics Seminar
Time:
Venue: Na
27 August 2019
NaDetecting repeat expansions associated with epilepsy
Mark BennettWEHI Population Health & Immunity
Repeat expansions are known to cause over 30 disorders ; including Huntington disease ; spinocerebellar ataxias and fragile X syndrome. Recently ; an intronic pentamer TTTCA repeat expansion was shown to cause familial adult myoclonic epilepsy 1 (FAME1) in a large number of families from Japan and China. In the last few years ; several methods have been developed ; including our method exSTRa ; to detect repeat expansions using next-generation sequencing. We identified the FAME1 repeat expansion in families of Sri Lankan and Indian origin. All affected individuals share a core haplotype ; suggesting this repeat expansion is an ancient mutation ; which is estimated to occur around 17 ;000 years ago and has since spread across Asia.
FAME1 is one of several recently discovered repeat expansions ; where the pathogenic repeat is not present in the reference genome. These are particularly challenging to detect. ExpansionHunter DeNovo is a new software tool we have developed that can identify repeat expansions without prior knowledge of the repeat motif or location ; which is not possible at present using the existing targeted methods. ExpansionHunter DeNovo was used to discover the novel repeat expansion which causes cerebellar ataxia ; neuropathy ; vestibular areflexia syndrome and can also identify the FAME expansion without prior knowledge.;;;