Genetic diversity, forensic characteristics and phylogenetic analysis of the Qiongzhong aborigines residing in the tropical rainforests of Hainan Island via 19 autosomal STRs.

BACKGROUND: The genetic landscape of the Qiongzhong aborigines, who reside in "the Heart of Hainan," is still unclear. The Goldeneye™ DNA ID System 20 A is available for forensic and population genetics applications. AIM: To obtain genetic polymorphisms of 19 autosomal STR loci in the Qiongzhong aborigines, and to explore the genetic relationships with a total of 69,132 people from forty-five populations. SUBJECTS AND METHODS: Genotype data on 19 autosomal STRs were collected from 724 Qiongzhong aborigines and phylogenetic relationships were conducted by multidimensional scaling analysis (MDS), principal component analysis (PCA) and neighbor-joining (N-J) phylogenetic tree construction. RESULTS: No evidence of deviation from Hardy-Weinberg equilibrium was identified. A total of 233 distinct alleles were observed with allele frequencies ranging from 0.0007 to 0.5375. The combined power of discrimination (CPD) and combined power of exclusion (CPE) for the 19 autosomal STR loci were 1-8.28 × 10-34 and 0.999999987, respectively. CONCLUSION: Our phylogenetic results demonstrated that (a) the populations of Southeast Asian countries have thorough integrations with southern China in terms of ethnicity and genetics due to long-term cultural and trade exchanges, and (b) based on genetic and linguistic analysis, the Qiongzhong aborigines have a close relationship with Fujian Han Chinese.HighlightsThe STR landscape of Qiongzhong aborigines inhabited in Hainan tropical rainforests was depicted by 19 autosomal STRs.A total of 69,132 people from forty-five populations were selected for a more extensive examination of genetic similarities and differences by multivariate statistical methods (MDS, PCA and N-J tree construction).The genetic analyses indicated that the populations of Southeast Asian countries are very genetically close to southern Chinese populations.From the genetic and linguistic perspective, the Qiongzhong aborigines have a close relationship with Han Chinese from Fujian Province.

Insights From Y-STRs: Forensic Characteristics, Genetic Affinities, and Linguistic Classifications of Guangdong Hakka and She Groups.

Guangdong province is situated in the south of China with a population size of 113.46 million. Hakka is officially recognized as a branch of Han Chinese, and She is the official minority group in mainland China. There are approximately 25 million Hakka people who mainly live in the East and North regions of China, while there are only 0.7 million She people. The genetic characterization and forensic parameters of these two groups are poorly defined (She) or still need to be explored (Hakka). In this study, we have genotyped 475 unrelated Guangdong males (260 Hakka and 215 She) with Promega PowerPlex® Y23 System. A total of 176 and 155 different alleles were observed across all 23 Y-STRs for Guangdong Hakka (with a range of allele frequencies from 0.0038 to 0.7423) and Guangdong She (0.0047-0.8605), respectively. The gene diversity ranged from 0.4877 to 0.9671 (Guangdong Hakka) and 0.3277-0.9526 (Guangdong She), while the haplotype diversities were 0.9994 and 0.9939 for Guangdong Hakka and Guangdong She, with discrimination capacity values of 0.8885 and 0.5674, respectively. With reference to geographical and linguistic scales, the phylogenetic analyses showed us that Guangdong Hakka has a close relationship with Southern Han, and the genetic pool of Guangdong Hakka was influenced by surrounding Han populations. The predominant haplogroups of the Guangdong She group were O2-M122 and O2a2a1a2-M7, while Guangdong She clustered with other Tibeto-Burman language-speaking populations (Guizhou Tujia and Hunan Tujia), which shows us that the Guangdong She group is one of the branches of Tibeto-Burman populations and the Huonie dialect of She languages may be a branch of Tibeto-Burman language families.

The forensic landscape and the population genetic analyses of Hainan Li based on massively parallel sequencing DNA profiling.

Due to the formation of the Qiongzhou Strait by climate change and marine transition, Hainan island was isolated from the mainland southern China during the Last Glacial Maximum. Hainan island, located at the southernmost part of China and separated from the Leizhou Peninsula by the Qiongzhou Strait, laid on one of the modern human northward migration routes from Southeast Asia to East Asia. The Hlai language-speaking Li minority, the second largest population after Han Chinese in Hainan island, is the direct descendants of the initial migrants in Hainan island and has unique ethnic properties and derived characteristics; however, the forensic-associated studies on Hainan Li population are still insufficient. Hence, 136 Hainan Li individuals were genotyped in this study using the MPS-based ForenSeq™ DNA Signature Prep Kit (DNA Primer Set A, DPMA) to characterize the forensic genetic polymorphism landscape, and DNA profiles were obtained from 152 different molecular genetic markers (27 autosomal STRs, 24 Y-STRs, 7 X-STRs, and 94 iiSNPs). A total of 419 distinct length variants and 586 repeat sequence sub-variants, with 31 novel alleles (at 17 loci), were identified across the 58 STR loci from the DNA profiles of Hainan Li population. We evaluated the forensic characteristics and efficiencies of DPMA, demonstrating that the STRs and iiSNPs in DPMA were highly polymorphic in Hainan Li population and could be employed in forensic applications. In addition, we set up three datasets, which included the genetic data of (i) iiSNPs (27 populations, 2640 individuals), (ii) Y-STRs (42 populations, 8281 individuals), and (iii) Y haplogroups (123 populations, 4837 individuals) along with the population ancestries and language families, to perform population genetic analyses separately from different perspectives. In conclusion, the phylogenetic analyses indicated that Hainan Li, with a southern East Asia origin and Tai-Kadai language-speaking language, is an isolated population relatively. But the genetic pool of Hainan Li influenced by the limited gene flows from other Tai-Kadai populations and Hainan populations. Furthermore, the establishment of isolated population models will be beneficial to clarify the exquisite population structures and develop specific genetic markers for subpopulations in forensic genetic fields.

Systematic Evaluation of a Novel 6-dye Direct and Multiplex PCR-CE-Based InDel Typing System for Forensic Purposes.

Insertion/deletion (InDel) polymorphisms, combined desirable characteristics of both short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs), are considerable potential in the fields of forensic practices and population genetics. However, most commercial InDel kits designed based on non-Asians limited extensive forensic applications in East Asian (EAS) populations. Recently, a novel 6-dye direct and multiplex PCR-CE-based typing system was designed on the basis of genome-wide EAS population data, which could amplify 60 molecular genetic markers, consisting of 57 autosomal InDels (A-InDels), 2 Y-chromosomal InDels (Y-InDels), and Amelogenin in a single PCR reaction and detect by capillary electrophoresis, simultaneously. In the present study, the DNA profiles of 279 unrelated individuals from the Hainan Li group were generated by the novel typing system. In addition, we collected two A-InDel sets to evaluate the forensic performances of the novel system in the 1,000 Genomes Project (1KG) populations and Hainan Li group. For the Universal A-InDel set (UAIS, containing 44 A-InDels) the cumulative power of discrimination (CPD) ranged from 1-1.03 × 10-14 to 1-1.27 × 10-18, and the cumulative power of exclusion (CPE) varied from 0.993634 to 0.999908 in the 1KG populations. For the East Asia-based A-InDel set (EAIS, containing 57 A-InDels) the CPD spanned from 1-1.32 × 10-23 to 1-9.42 × 10-24, and the CPE ranged from 0.999965 to 0.999997. In the Hainan Li group, the average heterozygote (He) was 0.4666 (0.2366-0.5448), and the polymorphism information content (PIC) spanned from 0.2116 to 0.3750 (mean PIC: 0.3563 ± 0.0291). In total, the CPD and CPE of 57 A-InDels were 1-1.32 × 10-23 and 0.999965, respectively. Consequently, the novel 6-dye direct and multiplex PCR-CE-based typing system could be considered as the reliable and robust tool for human identification and intercontinental population differentiation, and supplied additional information for kinship analysis in the 1KG populations and Hainan Li group.

Forensic characteristics and phylogenetic analyses of one branch of Tai-Kadai language-speaking Hainan Hlai (Ha Hlai) via 23 autosomal STRs included in the Huaxia™ Platinum System.

BACKGROUND: Hainan Island, located in the South China Sea and separated from the Leizhou Peninsula by Qiongzhou Strait, is the second largest island after Taiwan in China. With the expansion of Han Chinese and the gradual formation of "South Hlai and North Han", nowadays, Hainan Hlai is the second largest population after Han Chinese in Hainan Island. Ha Hlai, distributed in southwest and southern Hainan Island, is the dominant branch of Hlai and speaks Ha localism. METHODS: We utilized the Huaxia™ Platinum PCR Amplification System (including 23 autosomal STRs and 2 sex-linked markers) to obtain the first STR profiling batch of 657 Ha Hlai individuals (497 males and 160 females). In order to explore the genetic relationships between the studied Ha Hlai and other reference populations with different language families, population genetic analyses, including PCA, MDS, STRUCTURE, and phylogenetic analysis, were conducted based upon the raw data and allelic frequencies of the polymorphic autosomal STR markers. RESULTS: In total, 271 distinct alleles were observed at the 23 STR loci. The number of diverse alleles ranged from 7 at TPOX locus to 23 at FGA locus, and the allelic frequencies varied from 0.0008 to 0.5533. In addition, the CPE and CPD were 1-7.39 × 10-10 and 1-3.13 × 10-28 , respectively. The phylogenetic analyses indicated that Ha Hlai is a Tai-Kadai language-speaking and relatively isolated population which has a close genetic and geographical relationship with Hainan Hlai, and M95 is the dominant haplogroup in Ha Hlai (56.18%). CONCLUSION: The 23 autosomal STR genetic markers were highly polymorphic as well as potentially useful for forensic applications in Hainan Ha Hlai population. The phylogenetic analyses demonstrated that small geographic scale gene flows could not be ignored and the shaping of the unique gene pool for each population was the combination effects of geographic, language, and cultural isolations.

Carbanionic rearrangements of halomethylenecyclobutanes. Stereochemistry of the migrating group.

The unusual base-induced ring-enlargement of halomethylenecyclobutanes to 1-halocyclopentenes was examined with unsymmetrical and (13)C-labeled substrates to study regio- and stereochemical characteristics. Migration of a ring carbon atom (single migration) or simultaneous migration of a ring carbon atom and the halide (double migration) gives the ring-enlarged products. (13)C-labeling experiments established that both rearrangements occur with retention of configuration at the migrating center. These systems are suggested as models for the Fritsch-Buttenberg-Wiechell (FBW) rearrangement.

Optimization of halopemide for phospholipase D2 inhibition.

Halopemide, which was identified by HTS to inhibit phospholipase D2 (PLD2), provided the basis for an exploratory effort to identify potent inhibitors of PLD2 for use as inflammatory mediators. Parallel synthesis and purification were utilized to rapidly identify orally available amide analogs derived from indole 2-carboxylic acids with superior potency versus PLD2.

Preclinical pharmacology of lumiracoxib: a novel selective inhibitor of cyclooxygenase-2.

1. This manuscript presents the preclinical profile of lumiracoxib, a novel cyclooxygenase-2 (COX-2) selective inhibitor. 2. Lumiracoxib inhibited purified COX-1 and COX-2 with K(i) values of 3 and 0.06 microM, respectively. In cellular assays, lumiracoxib had an IC(50) of 0.14 microM in COX-2-expressing dermal fibroblasts, but caused no inhibition of COX-1 at concentrations up to 30 microM (HEK 293 cells transfected with human COX-1). 3. In a human whole blood assay, IC(50) values for lumiracoxib were 0.13 microM for COX-2 and 67 microM for COX-1 (COX-1/COX-2 selectivity ratio 515). 4. Lumiracoxib was rapidly absorbed following oral administration in rats with peak plasma levels being reached between 0.5 and 1 h. 5. Ex vivo, lumiracoxib inhibited COX-1-derived thromboxane B(2) (TxB(2)) generation with an ID(50) of 33 mg kg(-1), whereas COX-2-derived production of prostaglandin E(2) (PGE(2)) in the lipopolysaccharide-stimulated rat air pouch was inhibited with an ID(50) value of 0.24 mg kg(-1). 6. Efficacy of lumiracoxib in rat models of hyperalgesia, oedema, pyresis and arthritis was dose-dependent and similar to diclofenac. However, consistent with its low COX-1 inhibitory activity, lumiracoxib at a dose of 100 mg kg(-1) orally caused no ulcers and was significantly less ulcerogenic than diclofenac (P<0.05). 7. Lumiracoxib is a highly selective COX-2 inhibitor with anti-inflammatory, analgesic and antipyretic activities comparable with diclofenac, the reference NSAID, but with much improved gastrointestinal safety.