The first Korean genome sequence and analysis: full genome sequencing for a socio-ethnic group

Abstract

We present the first Korean individual genome sequence (SJK) and analysis results. The diploid genome of a Korean male was sequenced to 28.95-fold redundancy using the Illumina paired-end sequencing method. SJK covered 99.9% of the NCBI human reference genome. We identified 420,083 novel single nucleotide polymorphisms (SNPs) that are not in the dbSNP database. Despite a close similarity, significant differences were observed between the Chinese genome (YH), the only other Asian genome available, and SJK: (1) 39.87% (1,371,239 out of 3,439,107) SNPs were SJK-specific (49.51% against Venter's, 46.94% against Watson's, and 44.17% against the Yoruba genomes); (2) 99.5% (22,495 out of 22,605) of short indels (< 4 bp) discovered on the same loci had the same size and type as YH; and (3) 11.3% (331 out of 2920) deletion structural variants were SJK-specific. Even after attempting to map unmapped reads of SJK to unanchored NCBI scaffolds, HGSV, and available personal genomes, there were still 5.77% SJK reads that could not be mapped. All these findings indicate that the overall genetic differences among individuals from closely related ethnic groups may be significant. Hence, constructing reference genomes for minor socio-ethnic groups will be useful for massive individual genome sequencing.

Figure 1.

Classification and number of intragenic SNPs. Intragenic SNPs identified in SJK were classified as known or novel according to their presence in dbSNP. Then, the SNPs were further classified based on their locations within genic regions. nsSNPs indicate nonsynonymous SNPs.

Figure 2.

Comparisons of SNPs among (A) SJK, NA18507 (Yoruba), and HuRef (Venter's); (B) SJK, NA18507, and YH (Chinese); (C) SJK, YH, and HuRef; (D) SJK, NA18507, and Watson; (E) SJK, HuRef, and Watson; and (F) SJK, YH, and Watson.

Figure 3.

Homo- and heterozygous deletions in SJK genome detected by anomalously spaced read pairs. (A) Homozygous 2.3-kb genomic deletion; (B) heterozygous 5-kb genomic deletion. Pink and blue bars, large deletions detected by anomalously spaced read pairs; green bars, regularly spaced read pairs mapped by the ungapped alignment algorithm in MAQ; gray bars, regularly spaced read pairs mapped by Smith-Waterman gapped alignment algorithm in MAQ; and red bars, singletons (reads without mate pairs).

Figure 4.

SJK's genetic lineage. (A) Autosomal phylogenic tree. The sample, KOR00009, is SJK's mother. Colors indicate populations: black, YRI (Yoruba in Ibadan, Nigeria); blue, JPT (Japanese in Tokyo, Japan); green, CHB (Han Chinese in Beijing, China); red, KOR (Korean in South Korea); and violet, CEU (Utah residents with northern and western European ancestry from the CEPH collection). (B) Chromosome Y haplogroup lineage. Personal genome abbreviations and subhaplogroup information: E (E3b, NA18507: Yoruba), R (R1b*, HuRef (Venter): Caucasian), R (R1 (or P), James Watson: Caucasian), O2b (SJK: Korean), and O1 (O1a, YH genome: Han Chinese), (C) SJK's mtDNA ethno-geographic lineage. Only the mtDNA of SJK was annotated.