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In family 1, Integrative Genomics View ever (IGV) snapshot shows a homozygous deletion encompassing TANGO2 exons 3–9, identified in the proband (II-1) by trio long-read HiFi genome sequencing (GS). This deletion removes the stop codon of the gene, supporting a loss-of-function effect. In family 2, IGV snapshot reveals a homozygous in-frame deletion spanning TANGO2 exons 4–6, detected in the proband (II-5) and her affected, deceased older brother (II-1) through duo long-read HiFi GS. Because exons 3 and 7 are expected to remain in frame, this deletion might produce a smaller, nonfunctional protein or alternatively cause abnormal splicing leading to loss-of-function. For both deletions, characteristic soft-clipped reads are observed along with a complete loss of coverage in homozygous individuals.

Journal: Neurology: Genetics

Article Title: Long-Read HiFi Genome Sequencing Resolves Retrotransposon-Mediated Deletions in TANGO2 Deficiency Disorder

doi: 10.1212/NXG.0000000000200377

Figure Lengend Snippet: In family 1, Integrative Genomics View ever (IGV) snapshot shows a homozygous deletion encompassing TANGO2 exons 3–9, identified in the proband (II-1) by trio long-read HiFi genome sequencing (GS). This deletion removes the stop codon of the gene, supporting a loss-of-function effect. In family 2, IGV snapshot reveals a homozygous in-frame deletion spanning TANGO2 exons 4–6, detected in the proband (II-5) and her affected, deceased older brother (II-1) through duo long-read HiFi GS. Because exons 3 and 7 are expected to remain in frame, this deletion might produce a smaller, nonfunctional protein or alternatively cause abnormal splicing leading to loss-of-function. For both deletions, characteristic soft-clipped reads are observed along with a complete loss of coverage in homozygous individuals.

Article Snippet: Long-read HiFi GS was performed on blood-derived genomic DNA from affected individuals in both families using the Revio system (Pacific Biosciences).

Techniques: Sequencing