Claire Anderson from the University College London in the UK presented at London Calling a short session on “Adaptive sampling reveals pathogenic repeat expansion underlying spinocerebellar ataxia.” Spinocerebellar Ataxia Type 4 (SCA4) is an autosomal dominant hereditary ataxia characterized by sensory neuropathy, explained Anderson. The locus has been linked to chromosome sixteen. Anderson and their mentor hypothesized that the elusive nature of SCA4 may be due to complex structural variants. For this, they used real-time enrichment through adaptive sampling for 16q. The research team used this approach to sequence lymphoblast/blood-derived gDNA from two families from Utah and Iowa. The ZFHX4 gene was identified along with a rare pathogenic exonic GGC repeat. SCA4 disease is rare, and Anderson noted that it may be due to a Swedish founder effect. Anderson noted that they are also analyzing genome information from the 1000 Genomes Project. Anderson’s adaptive sampling approach helped identify this structural variant that had remained unknown for twenty-eight years.
