Han Jun Jin

Y-chromosomal DNA haplogroups and their implications for the dual origins of the Koreans

We have analyzed eight Y-chromosomal binary markers (YAP, RPS4Y711, M9, M175, LINE1, SRY+465, 47z, and M95) and three Y-STR markers (DYS390, DYS391, and DYS393) in 738 males from 11 ethnic groups in east Asia in order to study the male lineage history of Korea. Haplogroup DE-YAP was found at a high frequency only in Japan but was also present at low frequencies in northeast Asia, including 2.5% in Korea, suggesting a northern origin for these chromosomes. Haplogroup C-RPS4Y711 was present in Korea and Manchuria at moderate frequencies: higher than in populations from southeast Asia, but lower than those in the northeast, which may imply a northern Asian expansion of these lineages, perhaps from Mongolia or Siberia. The major Y-chromosomal expansions in east Asia were those of haplogroup O-M175 (and its sublineages). This haplogroup is likely to have originated in southern east Asia and subsequently expanded to all of east Asia. The moderate frequency of one sublineage in the Koreans, haplogroup O-LINE1 (12.5%), could be a result of interaction with Chinese populations. The age of another sublineage, haplogroup O-SRY+465, and Y-STR haplotype diversity provide evidence for relatively recent male migration, originally from China, through Korea into Japan. In conclusion, the distribution pattern of Y-chromosomal haplogroups reveals the complex origin of the Koreans, resulting from genetic contributions involving the northern Asian settlement and range expansions mostly from southern-to-northern China.

Y-chromosomal STR haplotypes and their applications to forensic and population studies in east Asia

We have analyzed 11 Y-STR loci (DYS19, the two DYS385 loci, DYS388, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DXYS156Y) in 700 males from ten ethnic groups in east Asia in order to evaluate their usefulness for forensic and population genetic studies. A total of 644 different haplotypes were identified, among which 603 (86.14%) were individual-specific. The haplotype diversity averaged over all populations was 0.9997; using only the nine Y-STRs comprising the “minimal haplotype” (excluding DYS388 and DXYS156Y) it was 0.9996, a value similar to that found in 1924 samples from other Asian populations (0.9996; Lessig et al. Legal Medicine 5(2003) 160–163), and slightly higher than in European populations (0.9976; n=11,610; Roewer et al. For Sci International (2001) 118:103–111). All of the individual east Asian populations examined here had high haplotype diversity (≥0.997), except for the Mongolians (0.992) and Manchurians (0.960). The most frequent haplotype identified by the nine markers was present at only 1% (7/700). Population comparisons based on ΦST or ρ genetic distance measures revealed clustering according to the traditional northeast–southeast distinction, but with exceptions. For example, the Yunnan population from southern China lay among the northern populations, possibly reflecting recent migration, while the Korean population, traditionally considered northern, lay at the boundary between northern and southern populations. An admixture estimate suggested 55(51–59)% northern, 45(41–49)% southern contribution to the Koreans, illustrating the complexity of the genetic history of this region.

Y-Chromosome multiplexes and their potential for the DNA profiling of Koreans

Abstract We have developed four multiplex genotyping systems (GeneKin Y-STR multiplexes) using silver staining with allelic ladders for ten Y-chromosome STR markers (DYS19, DYS385, DYS388, DYS389I/II, DYS390, DYS391, DYS392, DYS393 and DXYS156Y), with a view towards the application of rapid and simple genotyping assay methods for DNA profiling. The GeneKin Y-STR multiplexes developed have followed the published nomenclature and ISFG guidelines for STR analysis. Allele and haplotype frequencies at these Y-STRs loci were analysed by PCR amplification using the GeneKin Y-STR multiplexes, followed by denaturing polyacrylamide gel electrophoresis in 316 unrelated males in the Korean population. A total of 295 different haplotypes were found, 279 of them being unique. Gene diversity ranged from 0.4026 at DYS391 to 0.9606 at DYS385. The haplotype diversity value (which is the same as the discrimination index) calculated from all ten loci combined was 0.9995, which is informative. Our results revealed that a set of ten Y-STRs can discriminate between most of the male individuals in the Korean population (discrimination capacity: 93.35%). The Y-STR multiplexes thus provide useful information for forensic analysis and paternity tests and can also be of great benefit for providing information not normally available from autosomal DNA systems.

Y-chromosome STR haplotype profiling in the Korean population

Allele and haplotype frequencies of seven Y-chromosome STR loci were determined from a sample of 330 unrelated males in the Korean population.

Korean population genetic data for eleven STR loci

Allele frequency and forensic parameters for eleven STR loci were surveyed in a random sample from the Korean population.

Forensic genetic analysis of nine miniSTR loci in the Korean population

Nine miniSTR loci were analyzed in 191 unrelated individuals from Korea using three multiplex PCR systems (multiplex I: D1S1677, D2S441 and D4S2364; multiplex II: D10S1248, D14S1434 and D22S1045; multiplex III: D12S391, D16S3253 and D20S161). Due to the short PCR amplicons (< 145 bp), miniSTR systems can effectively be used in forensic analysis with highly degraded DNAs. Allele frequencies and forensic parameters were calculated to evaluate their usefulness in forensic casework. The Exact Test demonstrated that all loci surveyed here were found to be no deviation from Hardy-Weinberg equilibrium, except two miniSTR markers (D4S2364 and D16S3253). When we compared the distribution of genetic variation of six miniSTR markers (D1S1677, D2S441, D4S2364, D10S1248, D14S1434 and D22S1045), the Exact Test revealed significant differences (P < 0.05) between the Korean sample studied here and almost all of other samples of East Asian and European populations. The combined probability of match calculated from nine miniSTR loci was 1.28 x 10(-8), which is high degree of polymorphism. Thus, the miniSTR system, combined with other valuable miniSTR markers, may be suitable for recovering useful information in analyzing degraded DNA samples.

Mitochondrial haplogroup B is negatively associated with elite Korean endurance athlete status

Mitochondrial DNA (mtDNA) mutations could contribute to aerobic performance, since they provide information to generate aerobic ATP energy by oxidative phosphorylation (OXPHOS) in their respiratory chain. Owing to haploid and absence of recombination, specific mutations in the mtDNA genome associated with human exercise tolerance or intolerance arise and remain in particular genetic lineages referred to as haplogroups. Recent studies have suggested that certain mtDNA lineages were associated with individual differences in trainability and physical capacity, but their origins and replicate test remain to be elucidated. We have therefore analyzed mtDNA haplogroup B variants to assess the possible role of the lineages to differences in elite athletic performance in a population-based case-control study in Cheonan, Korea. We demonstrated a significant negative association between mtDNA haplogroup B and the status of elite endurance athlete [n=378, odds ratio = 0.37 (95% CI: 0.14–0.97, p = 0.016)]. Thus, our results imply that specific mtDNA lineages may provide a significant effect on elite Korean endurance status, although larger sample sizes functional studies are necessary to further substantiate these findings.

Association of Monoamine Oxidase A (MAOA) Gene uVNTR and rs6323 Polymorphisms with Attention Deficit and Hyperactivity Disorder in Korean Children

Objective: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. The genetic cause of ADHD is still unclear, but the dopaminergic, serotonergic, and noradrenergic pathways have shown a strong association. In particular, monoamine oxidase A (MAOA) plays an important role in the catabolism of these neurotransmitters, suggesting that the MAOA gene is associated with ADHD. Therefore, we evaluated the relationship between the MAOA gene polymorphisms (uVNTR and rs6323) and ADHD. Materials and methods: We collected a total of 472 Korean children (150 ADHD cases and 322 controls) using the Korean version of the Dupaul Attention Deficit Hyperactivity Disorder Rating Scales (K-ARS). Genotyping was performed by PCR and PCR-RFLP. The Behavior Assessment System for Children Second Edition (BASC-2) was used to evaluate the problem behaviors within ADHD children. Results: We observed significant associations between the rs6323 and ADHD in girls (p < 0.05) and the TT genotype was observed as a protective factor against ADHD in the recessive model (OR 0.31, 95% CI 0.100–0.950, p = 0.022). The 3.5R-G haplotype showed a significant association in ADHD boys (p = 0.043). The analysis of subtype also revealed that the 4.5R allele of uVNTR was a risk factor for the development of ADHD in the combined symptom among girls (OR 1.87, 95% CI 1.014–3.453, p = 0.031). In the BASC-2 analysis, the MAOA uVNTR polymorphism was associated with activities of daily living in ADHD boys (p = 0.017). Conclusion: These results suggest the importance of the MAOA gene polymorphisms in the development of ADHD in Korean children. A larger sample set and functional studies are required to further elucidate of our findings.

Genetic associations between ADHD and dopaminergic genes (DAT1 and DRD4) VNTRs in Korean children

It is well known that dopaminergic genes affect the development of attention deficit hyperactivity disorder (ADHD) in various populations. Many studies have shown that variable number tandem repeats (VNTRs) located within the 3′-untranslated region of DAT1 and in exon 3 of DRD4 are associated with ADHD development; however, these results were inconsistent. Therefore, we investigated the genetic association between two VNTRs and ADHD in Korean children. We determined the VNTRs using PCR. We examined genotype and allele frequency differences between the experimental and control groups, along with the odds ratios, using Chi square and exact tests. We observed a significant association between the children with ADHD and the control group in the 10R/10R genotype of DAT1 VNTRs (p = 0.025). In addition, the 11R allele of DAT1 VNTRs showed a higher frequency in the control group than in the ADHD group (p = 0.023). Also, the short repeat (without 11R) and long repeat alleles (including 11R) were associated with ADHD (p < 0.05). The analysis of DRD4 VNTRs revealed that the 2R allele is associated with ADHD (p = 0.025). A significant result was also observed in long and short repeats (p < 0.05). Additionally, ADHD subtypes showed that the DRD4 VNTRs are associated with combined and hyperactive-impulsive subtype groups (p < 0.05). Therefore, our results suggest that DAT1 VNTRs and DRD4 VNTRs play a role in the genetic etiology of ADHD in Korean children.

Meeting report: The biology of genomes and proteomes

A mini-symposium of the Genetics Society of Korea was held at Dankook University, Korea on April 24, 2015. The theme of the mini-symposium was ‘The biology of genomes and proteomes.’ This was the first mini-symposium of 2015. There were two sessions that were chaired by Dr. Kyu-Dong Han (Dankook University, Korea) and Dr. Heui-Soo Kim (Pusan National University, Korea). In the first session, three speakers gave talks on genomics and epigenomics. The first speaker, Dr. Keunsoo Kang (Department of Microbiology, Dankook University, Korea), introduced ‘‘An automated analysis pipeline for a large set of ChIP-seq data: AutoChIP (Kim et al. 2014a, b).’’ Recent advances in genomic DNA sequencing have revolutionized the ways to examine molecular events inside cells in several aspects. Next-generation sequencing approaches, which enable the rapid and accurate sequencing of short DNA fragments, have changed the ways researchers approach biological problems. For example, researchers can identify the genome-wide binding sites of proteins by using chromatin immune precipitation coupled with parallel sequencing (ChIP-seq) without any prior knowledge (Johnson et al. 2007; Robertson et al. 2007). Although there are many applications available for the analysis of ChIP-seq data (Henry et al. 2014), users need to know some details about the installation, alignment, and peak-calling procedures in most cases. Dr. Kang summarized his recent advances with the AutoChip assay, which is an easy-to-use application for ChIP-seq analysis. Using the AutoChip, the user automatically downloads and installs programs on his or her computer before launching the actual data analysis. In addition, all procedures for ChIP-seq analyses, such as the alignment of unmapped reads to a reference genome and the identification of genome-wide binding sites for a given protein, can be done by two simple steps coupled with AutoChIP. An evaluation of the cocktail algorithm implemented in AutoChIP showed that the algorithm outperformed a single ChIP-seq tool in terms of the ratio of motif occurrences and the average height of the normalized read density over the identified peaks. In addition, the annotation of the identified peaks with information about known genes and repeat elements provides a comprehensive picture of the genome-wide binding sites of selected proteins. Overall, AutoChIP provides a comprehensive platform to analyze a large set of ChIPseq data in one step. The second speaker, Dr. Kyunghwan Kim (Department of Biology, Chungbuk National University, Korea), gave a presentation entitled ‘Epigenetics and cancer development.’ The regulation of gene expression and the maintenance of chromosome stability in eukaryotes are critically associated with the formation of silent chromatin. Inactive chromatin structures are frequently related to distinctive histone modifications (Suganuma and Workman 2011). Although recent studies have implicated histone modification as a key regulator of chromatin fluidity, the molecular mechanisms underlying such effects remain & Nam-Soo Kim kimnamsu@kangwon.ac.kr