Human genetic variation database, a reference database of genetic variations in the Japanese population

Abstract

Whole-genome and -exome resequencing using next-generation sequencers is a powerful approach for identifying genomic variations that are associated with diseases. However, systematic strategies for prioritizing causative variants from many candidates to explain the disease phenotype are still far from being established, because the population-specific frequency spectrum of genetic variation has not been characterized. Here, we have collected exomic genetic variation from 1208 Japanese individuals through a collaborative effort, and aggregated the data into a prevailing catalog. In total, we identified 156 622 previously unreported variants. The allele frequencies for the majority (88.8%) were lower than 0.5% in allele frequency and predicted to be functionally deleterious. In addition, we have constructed a Japanese-specific major allele reference genome by which the number of unique mapping of the short reads in our data has increased 0.045% on average. Our results illustrate the importance of constructing an ethnicity-specific reference genome for identifying rare variants. All the collected data were centralized to a newly developed database to serve as useful resources for exploring pathogenic variations. Public access to the database is available at http://www.genome.med.kyoto-u.ac.jp/SnpDB/.

Genomic analysis identifies masqueraders of full‐term cerebral palsy

“…Nonsynonymous SNVs, splice‐site variants and indels were retained. We excluded variants present in the 1000 Genomes database, the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP6500), the Exome Aggregation Consortium (ExAC) database version 0.3 (all and East Asian populations), and the Human Genetic Variation Database (HGVD)18, 19 to discover rare de novo variants. For the autosomal recessive and X‐linked models, we excluded variants with an allele frequency equal to or greater than 1% in the 1000 Genomes database, the Exome Sequencing Project (ESP) 6500, the ExAC database version 0.3 (all and East Asian populations) and the HGVD.…”

Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals

“…Large-scale genome sequencing of volunteers from general residents provides valuable data for the field of medical genomics; however, whole genome sequencing (WGS) or whole exome sequencing (WES) [6,7] may uncover other clinically relevant variants in addition to specific findings intended by a particular project. Therefore, it raises an important problem: how can researchers use and manage secondary findings, which may be deliberately sought, or incidental findings (accidental discoveries) from WGS or WES studies?…”

Whole exome sequencing detects variants of genes that mediate response to anticancer drugs

“…The mutation frequencies of cancer types and minor allele frequencies (MAFs) detected are listed in Table 3. The MAFs of the variants did not differ significantly from those of normal subjects listed in the public database (Higasa et al, 2016;Yamaguchi-Kabata et al, 2015), suggesting that WES is useful for the comprehensive detection of germline mutations. Only the allele frequency of CDA (rs60369023) differed significantly from that in the public database, which is almost consistent with the results of another study (our calculated MAF was 0.028 compared to 0.022) (Sugiyama et al, 2009).…”

“…The allele frequencies of each gene were compared with those obtained from public databases, the Human Genetic Variation Database (HGVD) (Higasa et al, 2016) or the Integrative Japanese Genome Variation Database (iJGVD) (Yamaguchi-Kabata et al, 2015).…”