ToMMo has successfully analyzed structural variations in the Japanese population using a long-read sequencer. This study was published in the journal Communications Biology on September 20, 2022. The positions and frequencies of structural variants (SVs) identified in this study can be found on jMorp*, as a reference panel referred to as JSV1.
SVs are genomic rearrangements greater than 50 bp in size. ToMMo has conducted short-read whole-genome sequencing (WGS) analyses, and constructed allele frequency panel focusing on single-nucleotide variants (SNVs) and short insertions and deletions (indels). However, the conventional short-read sequencing technologies have limits in SV detection and database focusing on SVs for Japanese population have been desired.
Researchers of ToMMo conducted WGS analysis using long read sequencer, PromethION from Oxford Nanopore Technologies. The long-read sequencing technology can produce sequencing reads with several thousand base pairs or more, which enable us to capture larger SVs better than can be achieved with short-read sequencing alone. To address a requirement of a high-quality genomic DNA suitable to the long read sequencing, the researchers of ToMMo utilized activated T-lymphocytes as a biological resource. The activated T-lymphocytes are one of the unique biological resources which are established from blood specimens of cohort participants and stored in the TMM biobank. In total, 333 individuals were involved in this study, constituting 111 trios (adults and their biological parents). This trio-based design allows an evaluation of the accuracy by analyzing results between parents and their offspring.
This reference panel of SVs in the general Japanese population was successfully constructed using high-coverage long-read sequencing data enabled by using the activated T-lymphocytes. The SVs identified were evaluated by the inheritance pattern observed in each trio. The reference panel would contribute to the diagnosis of rare diseases and to the analysis of cancer genomes, in which analyses focusing on small-sized variants alone have been insufficient.
*For the calculation of the frequencies of SVs, genotype information from 111 pairs of fathers and mothers, which are genetically unrelated, were used to avoid double counting the SVs shared between parents and offspring. Each SV is assigned the above accuracy verification result.
Title: Construction of a trio-based structural variation panel utilizing activated T lymphocytes and long-read sequencing technology
Authors: Akihito Otsuki, Yasunobu Okamura, Noriko Ishida, Shu Tadaka, Jun Takayama, Kazuki Kumada, Junko Kawashima, Keiko Taguchi, Naoko Minegishi, Shinichi Kuriyama, Gen Tamiya, Kengo Kinoshita, Fumiki Katsuoka, Masayuki Yamamoto
Journal: Communications Biology
Published date: 20 September 2022