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, and provides a critical resource that can be used to more accurately identify pathogenic genetic variants. 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 in order to characterize the benign ethnicity-relevant genetic variation present in the Korean population. 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 when prioritizing disease-causing variants. 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.

Korean Genome Project: 1094 Korean personal genomes with clinical information

“…Whole-genome sequencing (WGS) data from 1007 blood or saliva samples (984 samples with clinical and biochemical information) were generated with an average sequencing depth of 31× and pooled with sequencing data from an additional 87 blood or saliva samples (without clinical information) from the KoVariome database ( 9 ). In total, 1094 complete genomes, including 916 unrelated and healthy individuals, mostly from the Ulsan metropolitan region, were compared to the human genome reference (hg38).…”

“…On the other hand, less than 20% of the variants were classified as very common (allele frequency of >0.05), with more than 94% of these variants previously reported in dbSNP (v150) ( 20 ). A total of 96.6% of the very common SNVs overlapped with KoVariome ( 9 ), compared to only 12.4% of rare SNVs (fig. S3).…”

“…However, little formal scrutiny has been given to these claims. Several Korean whole genomes and exomes ( 5 , 6 ) have been reported since the first Korean genome data (SJK) were published in 2008 ( 7 ), including the first Korean reference genome sequence (KOREF_S) ( 8 ) and 40 unrelated individuals (KOREF_C) that formed the basis of KoVariome, the Korean genomic variation database ( 9 ). Before the current study, at least 100 whole genomes of Korean individuals were available worldwide ( 5 , 10 ).…”

“…In East Asia, the 1KJPN project yielded data on 1070 Japanese genomes ( 17 ), and another recent dataset identified selection signatures in the Japanese population from 2234 Japanese whole-genome data ( 18 ). In contrast, the original KoVariome database contained only 50 Korean whole-genome sequences without clinical information at the time of publication ( 9 ), although its sample size has subsequently increased to >100 genomes. Despite these large genome sequencing projects in numerous populations, little biochemical and clinical data and limited information regarding genotype-phenotype association for the participants have been collected to characterize the population’s health and disease states.…”

Genome Diversity in Ukraine

“…Majority of these described variants are rare or very rare (<5%; Figure S2). Unless other indigenous ethnic groups from Ukraine (such as Crimean Tatars), would be included in the study, increasing the sample size above from 100 to 1,000 individuals is not likely to greatly contribute to discovery of novel mutations [14]. The proportion of the novel structural variants and mobile elements compared to the earlier databases is even higher: almost 1M (909,991) complex indels, regions of simultaneous deletions and insertions of DNA fragments of different sizes which lead to net a change in length, majority of which are novel ( Table 1).…”