24029169
Genetic Characterization and Assessment of Authenticity of Ancient Korean Skeletal Remains
Abstract To study the maternal lineage history of Korea, we extracted DNA from the skeletal remains of 35 museum samples (some dating back to the Paleolithic Age) excavated from 11 local burial sites scattered throughout southern Korea. Mitochondrial DNA (mtDNA) control region sequences (HV1, HV2, and HV3) were successfully determined for 11 samples with no sharing of the control region polymorphisms with individuals involved in the laboratory analyses. Each of the 11 mtDNAs was assigned to the appropriate East Asian mtDNA haplogroup according to the haplogroup-specific control region mutation motif and diagnostic coding region single nucleotide polymorphism. The successful mtDNA haplogroup determination for each ancient Korean mtDNA and the confirmation of the absence of abnormal mutations based on the haplogroup-directed database comparisons indicates that there is no mosaic structure from cross-contamination or sample mix-up or other errors in our mtDNA sequences. The presence of haplogroups B, D, and G in the prehistoric age is consistent with the hypothesis that the early Korean population has a common origin in the northern regions of the Altai Mountains and Lake Baikal of southeastern Siberia. In addition, the modern Korean population, which possesses lineages from both southern and northern haplogroups, suggests additional gene flow from southern Asian haplogroups in recent times, but many more ancient samples need to be analyzed to directly tell whether there was regional continuity or replacement of early lineages by other lineages in ancient Korea.
22243051
Potential forensic application of DNA methylation profiling to body fluid identification
DNA analysis of various body fluid stains at crime scenes facilitates the identification of individuals but does not currently determine the type and origin of the biological material. Recent advances in whole genome epigenetic analysis indicate that chromosome pieces called tDMRs (tissue-specific differentially methylated regions) show different DNA methylation profiles according to the type of cell or tissue. We examined the potential of tissue-specific differential DNA methylation for body fluid identification. Five tDMRs for the genes DACT1, USP49, HOXA4, PFN3, and PRMT2 were selected, and DNA methylation profiles for these tDMRs were produced by bisulfite sequencing using pooled DNA from blood, saliva, semen, menstrual blood, and vaginal fluid. The tDMRs for DACT1 and USP49 showed semen-specific hypomethylation, and the tDMRs for HOXA4, PFN3, and PRMT2 displayed varying degrees of methylation according to the type of body fluid. Preliminary tests using methylation-specific PCR for the DACT1 and USP49 tDMRs showed that these two markers could be used successfully to identify semen samples including sperm cells. Body fluid-specific differential DNA methylation may be a promising indicator for body fluid identification. Because DNA methylation profiling uses the same biological source of DNA for individual identification profiling, the determination of more body fluid-specific tDMRs and the development of convenient tDMR analysis methods will facilitate the broad implementation of body fluid identification in forensic casework.
42434218
Differential distribution of human mitochondrial DNA in somatic tissues and hairs.
To investigate mitochondrial DNA (mtDNA) distribution within tissues during life, we observed length heteroplasmy in a polycytosine tract of the mitochondrial HV2 region by size-based separation of PCR products, using a mutagenic primer which was designed to avoid stutter production. Blood, brain, heart, liver, skeletal muscle and hair shaft samples were collected during autopsies of 25 individuals. Here, we demonstrate differences in the level of mtDNA length heteroplasmy both within and between individuals and tissues. We also show that mtDNA is distributed randomly in varying proportions in various somatic tissues during growth, resulting in an imbalance in the composition of mtDNA pools among tissues. This mtDNA distribution appears not to be strictly random, and can be explained by the random somatic segregation of nucleoids. On the other hand, significant qualitative/quantitative mtDNA peak pattern variations in hair shafts are thought to be a result of the different developmental origins of hairs. Each hair shaft may have a restricted or clonal set of mtDNA molecules derived from a discrete group of stem cells.
206716414
A one step multiplex PCR assay for rapid screening of East Asian mtDNA haplogroups on forensic samples.
The mitochondrial DNA (mtDNA) haplogroup typing has become an essential tool to study human evolutionary history and to infer the matrilineal bio-geographic ancestry. In forensic field, the screening of mtDNA haplogroups by genotyping of mtDNA single nucleotide polymorphisms (SNPs) can help guarantee the quality of mtDNA sequence data as well as can reduce the need to sequence samples that do not match. Here, a multiplex mutagenically separated (MS) polymerase chain reaction (PCR) system was developed for simultaneous rapid detection of 14 coding region SNPs and one deletion motif representing common mtDNA haplogroups of East Asia. The multiplex MS PCR system we developed has the advantage of being a one step procedure that requires only a single PCR amplification with allele-specific primers and allowing straightforward designation of haplogroups along the branches of the phylogenetic tree. Therefore, it would be a simple, rapid, and reliable detection method useful for large-scale screening of mtDNA variations to determine East Asian mtDNA haplogroups.
6681430
Haplotypes and mutation analysis of 22 Y-chromosomal STRs in Korean father–son pairs
We analyzed 369 Korean father/son haplotype transfers in 355 families at 22 Y-STRs (DYS19, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS385, DYS388, DYS437, DYS438, DYS439, DYS446, DYS447, DYS448, DYS449, DYS456, DYS458, DYS464, DYS635, and GATA H4.1). A total of 350 haplotypes were observed with an overall haplotype diversity of 0.9999. Among these, 345 were unique and five were found twice. Furthermore, 36 mutations were identified, giving locus-specific mutation rate estimates between 0.0 and 19.0 × 10−3 per generation and an average mutation rate estimate of 3.9 × 10−3 (95% CI 2.7–5.4 × 10−3). The compilation of Y-STR mutation events for the present study and previous studies demonstrates that DYS449, DYS458, DYS635, DYS456 and DYS439 are the most prone to mutations and that their overall average mutation rate estimate is 2.36 × 10–3 (95% CI 2.03–2.73 × 10–33).
29813959
DNA typing for the identification of old skeletal remains from Korean War victims.
The identification of missing casualties of the Korean War (1950-1953) has been performed using mitochondrial DNA (mtDNA) profiles, but recent advances in DNA extraction techniques and approaches using smaller amplicons have significantly increased the possibility of obtaining DNA profiles from highly degraded skeletal remains. Therefore, 21 skeletal remains of Korean War victims and 24 samples from biological relatives of the supposed victims were selected based on circumstantial evidence and/or mtDNA-matching results and were analyzed to confirm the alleged relationship. Cumulative likelihood ratios were obtained from autosomal short tandem repeat, Y-chromosomal STR, and mtDNA-genotyping results, and mainly confirmed the alleged relationship with values over 10⁵. The present analysis emphasizes the value of mini- and Y-STR systems as well as an efficient DNA extraction method in DNA testing for the identification of old skeletal remains.
32914971
Detection and characterization of focal hepatic lesions by T2-weighted imaging: comparison of navigator-triggered turbo spin-echo, breath-hold turbo spin-echo, and HASTE sequences.
The aim of this study is to evaluate the diagnostic performance of T(2)-weighted (T(2)-w) images obtained using navigator-triggered turbo spin-echo (TSE), breath-hold TSE (BH-TSE), and BH haft-Fourier single-shot TSE sequences for the detection and characterization of focal hepatic lesions. Two blinded reviewers independently analyzed three types of T(2)-w image sets totaling 86 solid and 75 nonsolid lesions in 59 patients. Receiver operating characteristic curves were established to analyze reviewer and sequence results.
7785683
Anterior clinoid process and optic strut in Koreans.
The anterior clinoid process and the optic strut are often removed during operation on the anterior part of the cavernous sinus. Therefore it is important for neurosurgeons to verify their dimensions and variations. The purpose of this study was to investigate the dimension and the variation of the anterior clinoid process and to describe the locational variation of the optic strut. Seventy-three skulls of Korean adults were used. The average length, basal width and thickness of the anterior clinoid process were 9.18 +/- 1.55, 9.63 +/- 1.49 and 5.32 +/- 1.07 mm, respectively. The average thickness of the optic strut was 2.9 +/- 1.15 mm and it was commonly attached to anterior two-fifths of the anterior clinoid process. The complete caroticoclinoid canal was observed in 4.1%, however it was incomplete in 11.6%. The incidence of a caroticoclinoid canal in Koreans was relatively low compared with other races.
25911131
Modeling sequence evolution in acute HIV-1 infection.
We describe a mathematical model and Monte Carlo (MC) simulation of viral evolution during acute infection. We consider both synchronous and asynchronous processes of viral infection of new target cells. The model enables an assessment of the expected sequence diversity in new HIV-1 infections originating from a single transmitted viral strain, estimation of the most recent common ancestor (MRCA) of the transmitted viral lineage, and estimation of the time to coalesce back to the MRCA. We also calculate the probability of the MRCA being the transmitted virus or an evolved variant. Excluding insertions and deletions, we assume HIV-1 evolves by base substitution without selection pressure during the earliest phase of HIV-1 infection prior to the immune response. Unlike phylogenetic methods that follow a lineage backwards to coalescence, we compare the observed data to a model of the diversification of a viral population forward in time. To illustrate the application of these methods, we provide detailed comparisons of the model and simulations results to 306 envelope sequences obtained from eight newly infected subjects at a single time point. The data from 68 patients were in good agreement with model predictions, and hence compatible with a single-strain infection evolving under no selection pressure. The diversity of the samples from the other two patients was too great to be explained by the model, suggesting multiple HIV-1-strains were transmitted. The model can also be applied to longitudinal patient data to estimate within-host viral evolutionary parameters.
29310135
Ground-glass opacity nodules: histopathology, imaging evaluation, and clinical implications.
Ground-glass opacity (GGO) nodules noted at thin-section computed tomography (CT) scan have been shown to have a histopathologic relationship with atypical adenomatous hyperplasia, bronchioloalveolar carcinoma (BAC, or adenocarcinoma in situ), and adenocarcinoma with a predominant BAC component (minimally invasive adenocarcinoma). Patients harboring GGO nodules of BAC or adenocarcinoma with a predominant BAC component demonstrate negative results for malignancy at positron emission tomography. In peripheral adenocarcinoma of a part-solid (mixed GGO and solid attenuation) nodular nature, both the degree of disappearance of GGO area, when the lung window is changed to a mediastinal window image at CT scanning, and the maximum standardized uptake value at positron emission tomography correlate well with histopathologic BAC and non-BAC ratios. However, a high non-BAC ratio appears to be the only independent prognosis-determining factor. Epidermal growth factor receptor mutations are positively correlated with the GGO ratio at a thin-section CT scan in lung adenocarcinomas. As patients with a GGO nodule of BAC or adenocarcinoma with a predominant BAC component have a good prognosis, a wedge resection is recommended as a treatment option, in preference to lobectomy. Even for multiple malignant pure GGO nodules, minimally invasive surgery (including multiple resections) with the preservation of lung volume and adequate imaging follow-up studies are the recommended diagnostic and therapeutic measures.
31653327
Rhabdoid Tumor of the Kidney Is a Component of the Rhabdoid Predisposition Syndrome 


The rhabdoid predisposition syndrome (RPS) is characterized by pedigrees in which two or more individuals carry germline mutations of the hSNF5/INI1 tumor suppressor gene. The tumors associated with the syndrome include atypical teratoid/rhabdoid tumor (AT/RT), choroid plexus carcinoma, medulloblastoma, and extrarenal rhabdoid tumor. Rhabdoid tumor of the kidney (RTK) has not been described as part of the RPS. We report a case of a 7-month-old boy with RTK whose sister had a malignant cerebellar tumor followed by a malignant lung and pleural tumor of childhood with typical rhabdoid histology. Molecular genetic analysis of the RTK and tissue from the pleural tumor revealed in both cases identical nonsense mutations of the hSNF5/INI1 gene on chromosome 22q11.2, where thymidine was substituted for cytosine in base 472. The proband had an identical germline mutation. This is the fifth genetically analyzed RPS pedigree and the first to include an RTK.
