Comparative Genomics Analysis Unit Research

National Human Genome Research Institute

Investigators

Linked publications, trials & patents

Abstract

Bioinformatics Developments In 2021, the CGAU continued to maintain and improve its SVanalyzer toolkit for the generation and analysis of structural variant calls, and this software is now being used for analysis by the National Institute of Standards and Technologys Genome in a Bottle project and the Telomere to Telomere (T2T) consortium. SVanalyzer is unique in its ability to reconcile different representations of structural variants in highly repetitive regions of the genome, which is a critical capability for analyzing highly complete genomes like the new T2T reference. We expect SVanalyzers relevance to increase as increasingly accurate long read technologies enable the detection of more and more complex structural events in genomes. Collaborative Work SAMD12 intronic repeat expansion For this publication, the CGAUs contribution was to scan exome data from family members with familial cortical myoclonic tremor with epilepsy (FCMTE), searching for an intronic repeat expansion in a restricted list of genes, one of which was SMAD12. Even though exome data does not enrich intronic regions, there were enough affected individuals and off-target reads to yield at least one sequence read-pair aligning to the suspected repeat expansion region in each affected individual. PCR validated this result in all affected individuals, and further follow-up with long-range PCR and PacBio sequencing of the resulting amplicons identified the precise sequence of the 4,000-5,000 base repeat expansion for individuals with the disease phenotype compared to an 83 to 107 base repeat length in those who are unaffected. (Zhou, Sood et al. 2021)