KoVariome: Korean National Standard Reference Variome database of whole genomes with comprehensive SNV, indel, CNV, and SV analyses

Abstract

High-coverage whole-genome sequencing data of a single ethnicity can provide a useful catalogue of population-specific genetic variations. Herein, we report a comprehensive analysis of the Korean population, and present the Korean National Standard Reference Variome (KoVariome). As a part of the Korean Personal Genome Project (KPGP), we constructed the KoVariome database using 5.5 terabases of whole genome sequence data from 50 healthy Korean individuals with an average coverage depth of 31×. In total, KoVariome includes 12.7M single-nucleotide variants (SNVs), 1.7M short insertions and deletions (indels), 4K structural variations (SVs), and 3.6K copy number variations (CNVs). Among them, 2.4M (19%) SNVs and 0.4M (24%) indels were identified as novel. We also discovered selective enrichment of 3.8M SNVs and 0.5M indels in Korean individuals, which were used to filter out 1,271 coding-SNVs not originally removed from the 1,000 Genomes Project data when prioritizing disease-causing variants. CNV analyses revealed gene losses related to bone mineral densities and duplicated genes involved in brain development and fat reduction. Finally, KoVariome health records were used to identify novel disease-causing variants in the Korean population, demonstrating the value of high-quality ethnic variation databases for the accurate interpretation of individual genomes and the precise characterization of genetic variations.

Whole-genome reference panel of 1,781 Northeast Asians improves imputation accuracy of rare and low-frequency variants

“…To illustrate the robustness of NARD as an imputation reference panel, we built a pseudo-GWAS dataset using an independent cohort of 97 unrelated KOR individuals 14,18,19 . It was generated from WGS data by masking the genotypes that were not included in the sites of Illumina Omni 2.5M array.…”

“…There are only a few population-scale WGS studies covering Northeast Asians from China, Japan, and Mongolia 6,8,12,13 , and these studies have the several issues for the improved reference panel in Northeast Asia such as public unavailability, inadequate sequencing coverage, and small sample size. Furthermore, although Koreans (KOR) are one of the major population groups in Northeast Asia, previous datasets for KOR [14][15][16] does not have enough number of WGS samples to accurately impute the genome-wide variants of KOR population. Therefore, constructing a large-scale whole-genome reference panel for the diverse population groups in Northeast Asia with deep sequencing coverage is still necessary to allow dense and accurate genotype imputation for the genetic researches in these populations.In this study, we constructed the Northeast Asian Reference Database (NARD), consisting of 1,781 individuals from Korea, Japan, Mongolia, China, and Hong Kong.…”

Analysis of miRNA inhibitors Efficacy using Capillary Electrophoresis with Laser-Induced Fluorescence

“…Sequence and data analysis were performed using Torrent Suite software (5.8.0). Sequencing coverage analysis was performed using coverage Analysis (5.8.0.1) plugins and VCF files were generated using the variantCaller To filter out potential sequencing background noise, we excluded Common Korean SNVs which are included in KoVariome whole genome sequence (WGS) database from 50 healthy unrelated Korean individuals 22,23 were also excluded. We identified possible impact of variants using SIFT, PolyPhen-2 and used OncoKDM to predict the effect of genetic variants on protein function [24][25][26][27] .…”

“…Annotation of the variants was obtained using the Ion Reporter (5.10.2.0) software.To filter out potential sequencing background noise, we excluded control variants detected in cfDNA or CTCs samples from 30 healthy individuals. Common Korean SNVs which are included in KoVariome whole genome sequence (WGS) database from 50 healthy unrelated Korean individuals22,23 were also excluded. We identified variants of uncertain significance (VUS) using SIFT, PolyPhen-2 and used…”

Comparison of Risk Allele Frequencies of Single Nucleotide Polymorphisms Associated With Age-Related Macular Degeneration in Different Ethnic Groups

“…The variant coordinates were based on the human genome assembly GRCh37. Because the East Asian data in the 1000 Genomes Project did not include data from Korean populations, we compared the data from ve continents and East Asian countries in the 1000 Genome Projects with data extracted from KRGDB, which included whole-genome sequencing data for 1722 Korean individuals [17]. Data on the population frequencies of the SNPs were downloaded from the web-based database (http://152.99.75.168:9090/KRGDB/menuPages/download.jsp/, last accessed: January 15, 2020).…”