Confirmation of Y haplogroup tree topologies with newly suggested Y-SNPs for the C2, O2b and O3a subhaplogroups

Kwon, S.Y.,Lee, H.Y.,Lee, E.Y.,Yang, W.I.,Shin, K.J. Elsevier Science 2015 FORENSIC SCIENCE INTERNATIONAL GENETICS Vol.19 No.-

Y chromosome single nucleotide polymorphisms (Y-SNPs) are useful markers for reconstructing male lineages through hierarchically arranged allelic sets known as haplogroups, and are thereby widely used in the fields such as human evolution, anthropology and forensic genetics. The Y haplogroup tree was recently revised with newly suggested Y-SNP markers for designation of several subgroups of haplogroups C2, O2b and O3a, which are predominant in Koreans. Therefore, herein we analyzed these newly suggested Y-SNPs in 545 unrelated Korean males who belong to the haplogroups C2, O2b or O3a, and investigated the reconstructed topology of the Y haplogroup tree. We were able to confirm that markers L1373, Z1338/JST002613-27, Z1300, CTS2657, Z8440 and F845 define the C2 subhaplogroups, C2b, C2e, C2e1, C2e1a, C2e1b and C2e2, respectively, and that markers F3356, L682, F11, F238/F449 and F444 define the O subhaplogroups O2b1, O2b1b, O3a1c1, O3a1c2 and O3a2c1c, respectively. Among six C2 subhaplogroups (C2b, C2e, C2e1*, C2e1a, C2e1b and C2e2), the C2e haplogroup and its subhaplogroups were found to be predominant, and among the four O2b subhaplogroups (O2b*, O2b1*, O2b1a and O2b1b), O2b1b was most frequently observed. Among the O3a subhaplogroups, O3a2c1 was predominant and it was further divided into the subhaplogroups O3a2c1a and O3a2c1c with a newly suggested marker. However, the JST002613-27 marker, which had been known to define the haplogroup C2f, was found to be an ancestral marker of the C2e haplogroup, as is the Z1338 marker. Also, the M312 marker for the O2b1 haplogroup designation was replaced by F3356, because all of the O2b1 haplotypes showed a nucleotide change at F3356, but not at M312. In addition, the F238 marker was always observed to be phylogenetically equivalent to F449, while both of the markers were assigned to the O3a1c2 haplogroup. The confirmed phylogenetic tree of this study with the newly suggested Y-SNPs could be valuable for anthropological and forensic investigations of East Asians including Koreans.

Analysis of 22 Y chromosomal STR haplotypes and Y haplogroup distribution in Pathans of Pakistan

Lee, E.Y.,Shin, K.J.,Rakha, A.,Sim, J.E.,Park, M.J.,Kim, N.Y.,Yang, W.I.,Lee, H.Y. Elsevier Science 2014 FORENSIC SCIENCE INTERNATIONAL GENETICS Vol.11 No.-

We analyzed haplotypes for 22 Y chromosomal STRs (Y-STRs), including 17 Yfiler loci (DYS19, DYS385a/b, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS437, DY438, DYS439, DYS448, DYS456, DYS458, DYS635 and Y-GATA-H4) and five additional STRs (DYS388, DYS446, DYS447, DYS449 and DYS464), and Y chromosomal haplogroup distribution in 270 unrelated individuals from the Pathans residing in the Federally Administered Tribal Areas and the North-West Frontier Province of Pakistan using in-house multiplex PCR systems. Each Y-STR showed diversities ranging from 0.2506 to 0.8538, and the discriminatory capacity (DC) was 73.7% with 199 observed haplotypes using 17 Yfiler loci. By the addition of 5 Y-STRs to the Yfiler system, the DC was increased to 85.2% while showing 230 observed haplotypes. Among the additional 5 Y-STRs, DYS446, DYS447 and DYS449 were major contributors to enhancing discrimination. In the analysis of molecular variance, the Pathans of this study showed significant differences from other Pathan populations as well as neighboring population sets. In Y-SNP analysis, a total of 12 Y chromosomal haplogroups were observed and the most frequent haplogroup was R1a1a with 49.3% frequency. To obtain insights on the origin of Pathans, the network analysis was performed for the haplogroups G and Q observed from the Pathans and the Jewish population groups including Ashkenazim and Sephardim, but little support for a Jewish origin could be found. In the present study, we report Y-STR population data in Pathans of Pakistan, and we emphasize the need for adding additional markers to the commonly used 17 Yfiler loci to achieve more improved discriminatory capacity in a population with low genetic diversity.

Haplotype and mutation analysis for newly suggested Y-STRs in Korean father-son pairs

Oh, Y.N.,Lee, H.Y.,Lee, E.Y.,Kim, E.H.,Yang, W.I.,Shin, K.J. Elsevier Science 2015 FORENSIC SCIENCE INTERNATIONAL GENETICS Vol.15 No.-

In this study, 363 Korean father-son haplotype transfers in 351 families were analyzed using an in-house multiplex PCR system for 14 Y-STRs (DYS385a/b, DYF387S1, DYS391, DYS449, DYS460, DYS481, DYS518, DYS533, DYS549, DYS570, DYS576, DYS627 and DYS643), that included 11 loci newly added to the PowerPlex Y23 system or the Yfiler Plus system. The Y-STRs showed gene diversity values ranging from 0.2499 to 0.9612; the multicopy Y-STR loci DYS385 and DYF387S1 had high gene diversity of 0.9612 and 0.9457, respectively. In addition, DYF387S1, which has two copies, showed three alleles in seven individuals, and micro-variant alleles were observed in 14 individuals at four loci (DYS448, DYS518, DYS570 and DYS627). Among 351 haplotypes for the 11 newly added Y-STRs, 350 different haplotypes were observed, with an overall haplotype diversity of 0.9999 and discrimination capacity of 99.72%. In 363 haplotype transfers from 351 pedigrees, 29 single-step mutations were observed at 11 Y-STRs. Locus-specific mutation rate estimates varied from 0.0 to 1.93x10<SUP>-2</SUP>, with an average estimated mutation rate of 6.66x10<SUP>-3</SUP>. Two father-son pairs had mutations at two different loci in 11 Y-STRs. The number of pairs with mutations at multiple loci increased to five when the mutation event was investigated for haplotype transfer at 28 Y-STRs including 17 Yfiler loci and 11 Y-STRs examined in this study: four father-son pairs had mutations at two loci, and one pair had mutations at three loci. Overall, mutations were frequently observed at DYS449, DYS576 and DYS627 loci, which are known to be rapidly mutating Y-STRs. Mutation rate estimates at most loci were not significantly different from rates in other populations, but estimates for DYF387S1, DYS518 and DYS570 were considerably lower in the Korean population than in other populations.

Investigation into the sequence structure of 23 Y chromosomal STR loci using massively parallel sequencing

Kwon, S.Y.,Lee, H.Y.,Kim, E.H.,Lee, E.Y.,Shin, K.J. Elsevier Science 2016 FORENSIC SCIENCE INTERNATIONAL GENETICS Vol.25 No.-

Next-generation sequencing (NGS) can produce massively parallel sequencing (MPS) data for many targeted regions with a high depth of coverage, suggesting its successful application to the amplicons of forensic genetic markers. In the present study, we evaluated the practical utility of MPS in Y-chromosome short tandem repeat (Y-STR) analysis using a multiplex polymerase chain reaction (PCR) system. The multiplex PCR system simultaneously amplified 24 Y-chromosomal markers, including the PowerPlex<SUP>®</SUP> Y23 loci (DYS19, DYS385ab, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS481, DYS533, DYS549, DYS570, DYS576, DYS635, DYS643, and YGATAH4) and the M175 marker with the small-sized amplicons ranging from 85 to 253bp. The barcoded libraries for the amplicons of the 24 Y-chromosomal markers were produced using a simplified PCR-based library preparation method and successfully sequenced using MPS on a MiSeq<SUP>®</SUP> System with samples from 250 unrelated Korean males. The genotyping concordance between MPS and the capillary electrophoresis (CE) method, as well as the sequence structure of the 23 Y-STRs, were investigated. Three samples exhibited discordance between the MPS and CE results at DYS385, DYS439, and DYS576. There were 12 Y-STR loci that showed sequence variations in the alleles by a fragment size determination, and the most varied alleles occurred in DYS389II with a different sequence structure in the repeat region. The largest increase in gene diversity between the CE and MPS results was in DYS437 at +34.41%. Single nucleotide polymorphisms (SNPs), insertions, and deletions (indels) were observed in the flanking regions of DYS481, DYS576, and DYS385, respectively. Stutter and noise ratios of the 23 Y-STRs using the developed MPS system were also investigated. Based on these results, the MPS analysis system used in this study could facilitate the investigation into the sequences of the 23 Y-STRs in forensic genetics laboratories.

NMR study of hydrogen exchange during the B-Z transition of a DNA duplex induced by the Zα domains of yatapoxvirus E3L

Lee, E.H.,Seo, Y.J.,Ahn, H.C.,Kang, Y.M.,Kim, H.E.,Lee, Y.M.,Choi, B.S.,Lee, J.H. North-Holland Pub ; Elsevier Science Ltd 2010 FEBS letters Vol.584 No.21

The Yaba-like disease viruses (YLDV) are members of the Yatapoxvirus family and have double-stranded DNA genomes. The E3L protein, which is essential for pathogenesis in the vaccinia virus, consists of two domains: an N-terminal Z-DNA binding domain and a C-terminal RNA binding domain. The crystal structure of the E3L orthologue of YLDV (yabZα<SUB>E3L</SUB>) bound to Z-DNA revealed that the overall structure of yabZα<SUB>E3L</SUB> and its interaction with Z-DNA are very similar to those of hZα<SUB>ADAR1</SUB>. Here we have performed NMR hydrogen exchange experiments on the complexes between yabZα<SUB>E3L</SUB> and d(CGCGCG)<SUB>2</SUB> with a variety of protein-to-DNA molar ratios. This study revealed that yabZα<SUB>E3L</SUB> could efficiently change the B-form helix of the d(CGCGCG)<SUB>2</SUB> to left-handed Z-DNA via the active-mono B-Z transition pathway like hZα<SUB>ADAR1</SUB>1.

A multiplex PCR system for 13 RM Y-STRs with separate amplification of two different repeat motif structures in DYF403S1a

Lee, E.Y.,Lee, H.Y.,Kwon, S.Y.,Oh, Y.N.,Yang, W.I.,Shin, K.J. ELSEVIER SCIENCE B V AMSTERDAM 2017 FORENSIC SCIENCE INTERNATIONAL GENETICS Vol.26 No.-

<P>In forensic science and human genetics, Y-chromosomal short tandem repeats (Y-STRs) have been used as very useful markers. Recently, more Y-STR markers have been analyzed to enhance the resolution power in haplotype analysis, and 13 rapidly mutating (RM) Y-STRs have been suggested as revolutionary tools that can widen Y-chromosomal application from paternal lineage differentiation to male individualization. We have constructed two multiplex PCR sets for the amplification of 13 RM Y-STRs, which yield small-sized amplicons (<400 bp) and a more balanced PCR efficiency with minimum PCR cycling. In particular, with the developed multiplex PCR system, we could separate three copies of DYF403S1a into two copies of DYF403S1a and one of DYF403S1b1. This is because DYF403S1b1 possesses distinguishable sequences from DYF403S1a at both the front and rear flanking regions of the repeat motif; therefore, the locus could be separately amplified using sequence-specific primers. In addition, the other copy, defined as DYF403S1b by Ballantyne et al., was renamed DYF403S1b2 because of its similar flanking region sequence to DYF403S1b1. By redefining DYF403S1 with the developed multiplex system, all genotypes of four copies could be successfully typed and more diverse haplotypes were obtained. We analyzed haplotype distributions in 705 Korean males based on four different Y-STR subsets: Yfiler, PowerPlex Y23, Yfiler Plus, and RM Y-STRs. All haplotypes obtained from RM Y-STRs were the most diverse and showed strong discriminatory power in Korean population. (C) 2016 Elsevier Ireland Ltd. All rights reserved.</P>

Association and functional relevance of E237G, a polymorphism of the high-affinity immunoglobulin E-receptor β chain gene, to airway hyper-responsiveness

Kim, Y.-K.,Park, H.-W.,Yang, J.-S.,Oh, S.-Y.,Chang, Y.-S.,Shin, E.-S.,Lee, J.-E.,Kim, S.,Gho, Y. S.,Cho, S.-H.,Min, K.-U.,Kim, Y.-Y. Blackwell Scientific Publications 2007 Clinical and experimental allergy Vol.37 No.4

<P>Summary</P><P>Background</P><P>The hyper-sensitivity reaction of IgE, with its high-affinity receptors (FcϵRI), is central to the phenomenon of atopic diseases.</P><P>Objective</P><P>To evaluate the genetic effects of non-synonymous single-nucleotide polymorphisms (SNPs) of FcϵRI on intermediate phenotypes of asthma, i.e. atopy and airway hyper-responsiveness (AHR), in the Korean general population.</P><P>Subjects and methods</P><P>Atopy and AHR were evaluated in a cohort of 2055 subjects, aged 10–18 years, using skin prick tests (SPTs) for common aeroallergens and total serum IgE and methacholine bronchial provocation tests. All FcϵRI-α, FcϵRI-β, and FcϵRI-γ gene exons of 24 healthy subjects were sequenced to locate informative non-synonymous SNPs (minor allele frequency >2%). Informative SNPs were then scored, using the high-throughput single base extension method. Relative risk (RR) was determined by multiple logistic regression analysis, after adjusting for confounding factors. The functional relevance of non-synonymous SNPs was analysed using the sorting intolerant from tolerant (SIFT) program.</P><P>Results</P><P>The SNP search found only one informative non-synonymous SNP in FcϵRI-β: E237G (minor allele frequency=0.21). The positive rate of AHR was lower among subjects with the 237<SUP>*</SUP>E allele than among those with 237<SUP>*</SUP>G [RR (95% confidence interval)=0.41 (0.19–0.89); <I>P</I>=0.01]. However, the E237G substitution was not associated with either a positive SPT response or total serum IgE levels. Sequence evolution analysis predicted that the E237G variation is an intolerant amino acid substitution, with functional importance.</P><P>Conclusion</P><P>In the Korean general population, AHR is significantly associated with the E237G polymorphism of FcϵRI-β, which results in an intolerant amino acid substitution.</P>

딥러닝 기법을 이용한 전해가공의 홀가공 특성 분석

최승건(S. G. Choi),김준영(J. Y. Kim),이은상(E. S. Lee) 한국생산제조학회 2019 한국생산제조시스템학회 학술발표대회 논문집 Vol.2019 No.5

A novel chimeric promoter that is highly responsive to hypoxia and metals

Lee, J-Y,Lee, Y-S,Kim, J-M,Kim, K L,Lee, J-S,Jang, H-S,Shin, I-S,Suh, W,Jeon, E-S,Byun, J,Kim, D-K Nature Publishing Group 2006 Gene Therapy Vol.13 No.10

To develop a potent hypoxia-inducible promoter, we evaluated the usefulness of chimeric combinations of the (Egr-1)-binding site (EBS) from the Egr-1 gene, the metal-response element (MRE) from the metallothionein gene, and the hypoxia-response element (HRE) from the phosphoglycerate kinase 1 gene. In transient transfection assays, combining three copies of HRE (3 × HRE) with either EBS or MRE significantly increased hypoxia responsiveness. When a three-enhancer combination was tested, the EBS–MRE-3 × HRE (E–M–H) gave a hypoxia induction ratio of 69. The expression induced from E–M–H-pGL3 was 2.4-fold higher than that induced from H-pGL3 and even surpassed the expression from a human cytomegalovirus promoter-driven vector. The high inducibility of E–M–H was confirmed by validation studies in different cells and by expressing other cDNAs. Gel shift assays together with functional overexpression studies suggested that increased levels of hypoxia-inducible factor 1α, metal transcription factor-1 and Egr-1 may be associated with the high inducibility of the E–M–H chimeric promoter. E–M–H was also induced by hypoxia mimetics such as Co<SUP>2+</SUP> and deferoxamine (DFX) and by hydrogen peroxide. Gene expression from the E–M–H was reversible as shown by the reduced expression of the transgene upon removal of inducers such as hypoxia and DFX. In vivo evaluation of the E–M–H in ischemic muscle revealed that erythropoietin secretion and luciferase and LacZ expression were significantly higher in the E–M–H group than in a control or H group. With its high induction capacity and versatile means of modulation, this novel chimeric promoter should find wide application in the treatment of ischemic diseases and cancer.Gene Therapy (2006) 13, 857–868. doi:10.1038/sj.gt.3302728; published online 9 February 2006

Novel dentin phosphoprotein frameshift mutations in dentinogenesis imperfecta type II

Lee, K‐,E,Kang, H‐,Y,Lee, S‐,K,Yoo, S‐,H,Lee, J‐,C,Hwang, Y‐,H,Nam, KH,Kim, J‐,S,Park, J‐,C,Kim, J‐,W Blackwell Publishing Ltd 2011 Clinical genetics Vol.79 No.4

<P>Lee K‐E, Kang H‐Y, Lee S‐K, Yoo S‐H, Lee J‐C, Hwang Y‐H, Nam KH, Kim J‐S, Park J‐C, Kim J‐W. Novel dentin phosphoprotein frameshift mutations in dentinogenesis imperfecta type II.</P><P>The dentin sialophosphoprotein (<I>DSPP</I>) gene encodes the most abundant non‐collagenous protein in tooth dentin and DSPP protein is cleaved into several segments including the highly phosphorylated dentin phosphoprotein (DPP). Mutations in the <I>DSPP</I> gene have been solely related to non‐syndromic form of hereditary dentin defects. We recruited three Korean families with dentinogenesis imperfecta (DGI) type II and sequenced the exons and exon–intron boundaries of the <I>DSPP</I> gene based on the candidate gene approach. Direct sequencing of PCR products and allele‐specific cloning of the highly repetitive exon 5 revealed novel single base pair (bp) deletional mutations (c.2688delT and c.3560delG) introducing hydrophobic amino acids in the hydrophilic repeat domain of the DPP coding region. All affected members of the three families showed exceptionally rapid pulp chambers obliteration, even before tooth eruption. Individuals with the c.3560delG mutation showed only mild, yellowish tooth discoloration, in contrast to the affected individuals from two families with c.2688delT mutation. We believe that these results will help us to understand the molecular pathogenesis of DGI type II as well as the normal process of dentin biomineralization.</P>