Y chromosome haplogroup N in a Japanese population is classified into three subclades, and two DYS385 loci, a duplicated Y-STR, are duplicated again in subclade N-M1819.

DYS385 is one of the major Y chromosome short tandem repeats (Y-STRs) in forensic genetics and exists as 2 copies in the human Y chromosome palindrome P4 region. In this study, we found that some samples were estimated to have ≥ 4 copies of DYS385 in Y chromosome haplogroup N in a Japanese population. Y chromosome haplogroup N is distributed widely in eastern/central Asia, Siberia, and eastern/northern Europe, and is also observed in Japan; however, little is known about haplogroup N subclades in the Japanese population.

Development and validation of a SYBR green-based mitochondrial DNA quantification method by following the MIQE and other guidelines.

In forensic mitochondrial DNA (mtDNA) analysis, quantitative PCR (qPCR) is usually performed to obtain high-quality sequence data for subsequent Sanger or massively parallel sequencing. Unlike methods for nuclear DNA quantification using qPCR, a calibrator is necessary to obtain mtDNA concentrations (i.e.

Massively parallel sequencing data of 31 autosomal STR loci obtained using the Precision ID GlobalFiler NGS STR Panel v2 for 82 Japanese population samples.

Allele frequencies for 31 autosomal short tandem repeat (STR) loci (CSF1PO, D10S1248, D12ATA63, D12S391, D13S317, D14S1434, D16S539, D18S51, D19S433, D1S1656, D1S1677, D21S11, D22S1045, D2S1338, D2S1776, D2S441, D3S1358, D3S4529, D4S2408, D5S2800, D5S818, D6S1043, D6S474, D7S820, D8S1179, FGA, Penta D, Penta E, TH01, TPOX, and vWA) were obtained using Precision ID GlobalFiler NGS STR Panel v2 from 82 unrelated individuals sampled from the Japanese population. Autosomal STR alleles designated by NGS and conventional capillary electrophoresis were found to be concordant except at D2S441 allele 9.

Poly_NumtS_430 or HSA_NumtS_587 observed in massively parallel sequencing of the mitochondrial HV1 and HV2 regions.

An increasing number of studies on massively parallel sequencing of mitochondrial DNA (mtDNA) have been reporting identification of various types of noise or off-target sequences. Herein, we report that an off-target haplotype (sequence length 192 bp) observed in MiSeq data of mtDNA at nucleotide position 16,209-16,400 was likely caused by polymorphic nuclear mitochondrial DNA sequences (NumtS). Buccal DNA samples from Volunteers #001-004 and Control DNA 007 were amplified with our multiplex system of the B (15,998-16,172), C (16,209-16,400), and E (30-289) regions using 2000 copies of mtDNA.

Frequencies of D19S433 silent alleles in a Japanese population of 1501 individuals and their effect on likelihood ratios calculated in kinship tests.

Although silent alleles in D19S433 typing using the GlobalFiler PCR Amplification Kit have been reported, the exact frequency of the D19S433 silent alleles in population data of 1501 Japanese individuals, which are widely used for the assessment of Japanese STR typing results, is unclear. In this study, we examined the exact D19S433 silent allele frequency in this population data. We newly observed the G32A variant causing silent alleles at D19S433 in five samples.

-Non-flat substituents: a novel molecular design to improve aqueous solubility in small molecule drug discovery.

Aqueous solubility is a key requirement for small-molecule drug candidates. Here, we investigated the regioisomer-physicochemical property relationships of disubstituted benzenes. We found that meta-isomers bearing non-flat substituents tend to possess the lowest melting point and the highest thermodynamic aqueous solubility among the regioisomers.

Differences in DYF387S1 copy number distribution among haplogroups caused by haplogroup-specific ancestral Y-chromosome mutations.

DYF387S1 is a major Y-chromosome short tandem repeat (Y-STR) used in forensic genetics that is included in the Y-chromosomal haplotype reference database (YHRD, https://yhrd.org) and it is known as a rapidly mutating Y-STR. DYF387S1 is a multi-locus marker and the two paralogs are within a palindromic sequence which is a region prone to structural chromosome mutation.

Evaluation of Rapid DNA system for buccal swab and disaster victim identification samples.

An evaluation of a Rapid DNA system was performed using buccal swab samples and mock Disaster Victim Identification (DVI) samples collected postmortem. The allelic ladder success rate was 90% and samples analyzed simultaneously with this allelic ladder were used for further analysis. Sample success rate of the Rapid DNA system for buccal swab samples, and blood and muscle DVI samples were calculated.

Polymorphisms and microvariant sequences in the Japanese population for 25 Y-STR markers and their relationships to Y-chromosome haplogroups.

Y-chromosomal short tandem repeat (Y-STR) markers have been used for forensic purposes such as kinship analysis of male-linage and detection of a male DNA component in a mixture of male and female DNA. Recently, rapidly mutating Y-STR (RM Y-STR) markers were reported that are expected to help distinguish close male relatives. This study provides data of Y-chromosomal haplotypes for 25 Y-STR markers, including six RM Y-STR markers (DYS576, DYS627, DYS518, DYS570, DYS449 and DYF387S1) typed with the Yfiler™ Plus kit in 1299 males of the Japanese population.

Ratios and distances of pull-up peaks observed in GlobalFiler kit data.

Short tandem repeat (STR) analysis is widely used for forensic examinations with a capillary electrophoresis instrument such as the 3500xL Genetic Analyzer. This instrument adapts multi-locus STR kits to examine up to 27 loci using a 6-fluorescent dye system and corrects the spectral overlap between each dye. However, inaccurate spectral correction can cause pull-up peaks.

Next-generation sequencing analysis of off-ladder alleles due to migration shift caused by sequence variation at D12S391 locus.

In short tandem repeat (STR) analysis, length polymorphisms are detected by capillary electrophoresis (CE). At most STR loci, mobility shift due to sequence variation in the repeat region was thought not to affect the typing results. In our recent population studies of 1501 Japanese individuals, off-ladder calls were observed at the D12S391 locus using PowerPlex Fusion in nine samples for allele 22, one sample for allele 25, and one sample for allele 26.

D5S818 Typing Discrepancy Between PowerPlex(®) Fusion and Other STR Kits Including GlobalFiler(®) Caused by a One-base Deletion in 31 Nucleotides Upstream of the Repeat Region.

Short tandem repeat (STR) typing is widely used in forensic investigation. When the same DNA sample is analyzed with different STR typing kits, a typing discrepancy is occasionally observed. In this study, we examined the cause of a typing discrepancy in a sample at D5S818 locus.

Allele frequencies for 21 autosomal short tandem repeat loci obtained using GlobalFiler in a sample of 1501 individuals from the Japanese population.

Allele frequencies for 21 autosomal short tandem repeat loci (D3S1358, vWA, D16S539, CSF1PO, TPOX, D8S1179, D21S11, D18S51, D2S441, D19S433, TH01, FGA, D22S1045, D5S818, D13S317, D7S820, SE33, D10S1248, D1S1656, D12S391, and D2S1338) were obtained using the GlobalFiler kit from 1501 unrelated individuals sampled from the Japanese population.

Development of 2-thioxoquinazoline-4-one derivatives as dual and selective inhibitors of dynamin-related protein 1 (Drp1) and puromycin-sensitive aminopeptidase (PSA).

An established inhibitor of dynamin-related protein 1 (Drp1), 3-(2,4-dichloro-5-methoxyphenyl)-2-thioxoquinazoline-4-one (mdivi-1), was recently reported also to show potent puromycin-sensitive aminopeptidase (PSA)-inhibitory activity. Herein, we report structural development of mdivi-1 derivatives and structure-activity relationship (SAR) analysis of the synthesized compounds, as well as the structurally related PSA-specific inhibitor 3-(2,6-diethylphenyl)quinazoline-2,4-dione (PAQ-22), with the aim of identifying key structural features for inhibitory activity in order to develop selective inhibitors of Drp1, which is a potential target for treatment of Huntington's disease. Among the synthesized compounds, 3-(4-chloro-3-methoxyphenyl)-2-thioxoquinazoline-4-one (10g) exhibited more potent Drp1-inhibitory activity than mdivi-1 with high selectivity for Drp1 over PSA.

Structure-activity relationship of benzodiazepine derivatives as LXXLL peptide mimetics that inhibit the interaction of vitamin D receptor with coactivators.

Suppression of vitamin D receptor (VDR)-mediated transcription is expected to be of therapeutic value in Paget's disease of bone. It is known that interaction between VDR and coactivators is necessary for VDR transactivation, and the interaction occurs when VDR recognizes an LXXLL peptide motif of coactivators. We previously reported that benzodiazepine derivatives designed as LXXLL peptide mimetics inhibited the interaction of VDR and coactivators, and reduced VDR transcription.

Small-molecular, non-peptide, non-ATP-competitive polo-like kinase 1 (Plk1) inhibitors with a terphenyl skeleton.

Polo-like kinase (Plk) 1 is a serine-threonine protein kinase that plays a role in cell division, and its overexpression is highly correlated with aggressiveness and prognosis of many cancers. We have designed, synthesized and evaluated a series of terphenyl compounds as inhibitors of the kinase activity of Plk1. Some of them act as non-ATP-competitive Plk1 inhibitors.

LXXLL peptide mimetics as inhibitors of the interaction of vitamin D receptor with coactivators.

Suppression of vitamin D receptor (VDR)-mediated transcription is expected be of therapeutic value in Paget's disease. Once an agonist activates VDR, recruitment of additional coactivator proteins is essential for transcription. Neither non-secosteroidal VDR antagonists nor non-peptide coactivator binding inhibitors for VDR have been reported so far.