Malaria resistance-related biological adaptation and complex evolutionary footprints inferred from one integrative Tai-Kadai-related genomic resource.

Pathogen‒host adaptative interactions and complex population demographical processes, including admixture, drift, and Darwen selection, have considerably shaped the Neolithic-to-Modern Western Eurasian population structure and genetic susceptibility to modern human diseases. However, the genetic footprints of evolutionary events in East Asia remain unknown due to the underrepresentation of genomic diversity and the design of large-scale population studies. We reported one aggregated database of genome-wide SNP variations from 796 Tai-Kadai (TK) genomes, including that of Bouyei first reported here, to explore the genetic history, population structure, and biological adaptative features of TK people from southern China and Southeast Asia. We found geography-related population substructure among TK people using the state-of-the-art population genetic structure reconstruction techniques based on the allele frequency spectrum and haplotype-resolved phased fragments. We found that the northern TK people from Guizhou harbored one TK-dominant ancestry maximized in the Bouyei people, and the southern TK people from Thailand were more influenced by Southeast Asians and indigenous people. We reconstructed fitted admixture models and demographic graphs, which showed that TK people received gene flow from ancient southern rice farmer-related lineages related to the Hmong-Mien and Austroasiatic people and from northern millet farmers associated with the Sino-Tibetan people. Biological adaptation focused on our identified unique TK lineages related to Bouyei, which showed many adaptive signatures conferring Malaria resistance and low-rate lipid metabolism. Further gene enrichment, the allele frequency distribution of derived alleles, and their correlation with the incidence of Malaria further confirmed that CR1 played an essential role in the resistance of Malaria in the ancient "Baiyue" tribes.

Differentiated adaptative genetic architecture and language-related demographical history in South China inferred from 619 genomes from 56 populations.

BACKGROUND: The underrepresentation of human genomic resources from Southern Chinese populations limited their health equality in the precision medicine era and complete understanding of their genetic formation, admixture, and adaptive features. Besides, linguistical and genetic evidence supported the controversial hypothesis of their origin processes. One hotspot case was from the Chinese Guangxi Pinghua Han people (GPH), whose language was significantly similar to Southern Chinese dialects but whose uniparental gene pool was phylogenetically associated with the indigenous Tai-Kadai (TK) people. Here, we analyzed genome-wide SNP data in 619 people from four language families and 56 geographically different populations, in which 261 people from 21 geographically distinct populations were first reported here. RESULTS: We identified significant population stratification among ethnolinguistically diverse Guangxi populations, suggesting their differentiated genetic origin and admixture processes. GPH shared more alleles related to Zhuang than Southern Han Chinese but received more northern ancestry relative to Zhuang. Admixture models and estimates of genetic distances showed that GPH had a close genetic relationship with geographically close TK compared to Northern Han Chinese, supporting their admixture origin hypothesis. Further admixture time and demographic history reconstruction supported GPH was formed via admixture between Northern Han Chinese and Southern TK people. We identified robust signatures associated with lipid metabolisms, such as fatty acid desaturases (FADS) and medically relevant loci associated with Mendelian disorder (GJB2) and complex diseases. We also explored the shared and unique selection signatures of ethnically different but linguistically related Guangxi lineages and found some shared signals related to immune and malaria resistance. CONCLUSIONS: Our genetic analysis illuminated the language-related fine-scale genetic structure and provided robust genetic evidence to support the admixture hypothesis that can explain the pattern of observed genetic diversity and formation of GPH. This work presented one comprehensive analysis focused on the population history and demographical adaptative process, which provided genetic evidence for personal health management and disease risk prediction models from Guangxi people. Further large-scale whole-genome sequencing projects would provide the entire landscape of southern Chinese genomic diversity and their contributions to human health and disease traits.

An analysis of POMC gene methylation and expression in patients with schizophrenia.

Schizophrenia is a chronic mental disorder that affects millions of people and is believed to be caused by both environmental and genetic factors. Despite extensive research, the exact mechanisms underlying schizophrenia are still unclear. Studies have shown that numerous psychiatric disorders are associated with methylation of the POMC gene, which encodes adrenocorticotropic hormone, a critical player in the hypothalamic-pituitary-adrenal axis. However, the association between DNA methylation in POMC patients and schizophrenia remains unclear. In this study, we evaluated three fragments of the POMC promoter region, including 51 CpG sites, in the peripheral blood of schizophrenia patients and healthy controls. The POMC protein level was measured via enzyme-linked immunosorbent assay (ELISA). The schizophrenia group exhibited significantly greater levels of methylation of the POMC gene than those in the control group. The methylation level of the POMC-2 fragment was significantly greater in the patient group than in the control group. There were 17 significantly hypermethylated CpG sites in the patient group. After stratification by sex, POMC methylation levels were found to be significantly greater in male schizophrenia patients than in healthy controls; the methylation levels of POMC-2 fragments were greater in the male patient group; nine CpG sites were significantly hypermethylated in the male patient group; and only one CpG site was significantly hypermethylated in the female patient group. The POMC protein level in patients was significantly lower than that in healthy controls. These findings demonstrate that the DNA methylation of POMC might be associated with the pathophysiology of schizophrenia. Overall, studying the correlation between POMC methylation and schizophrenia may contribute to the diagnosis and evaluation of neuropsychiatric disorders.

Differentiated genomic footprints suggest isolation and long-distance migration of Hmong-Mien populations.

BACKGROUND: The underrepresentation of Hmong-Mien (HM) people in Asian genomic studies has hindered our comprehensive understanding of the full landscape of their evolutionary history and complex trait architecture. South China is a multi-ethnic region and indigenously settled by ethnolinguistically diverse HM, Austroasiatic (AA), Tai-Kadai (TK), Austronesian (AN), and Sino-Tibetan (ST) people, which is regarded as East Asia's initial cradle of biodiversity. However, previous fragmented genetic studies have only presented a fraction of the landscape of genetic diversity in this region, especially the lack of haplotype-based genomic resources. The deep characterization of demographic history and natural-selection-relevant genetic architecture of HM people was necessary. RESULTS: We reported one HM-specific genomic resource and comprehensively explored the fine-scale genetic structure and adaptative features inferred from the genome-wide SNP data of 440 HM individuals from 33 ethnolinguistic populations, including previously unreported She. We identified solid genetic differentiation between HM people and Han Chinese at 7.64‒15.86 years ago (kya) and split events between southern Chinese inland (Miao/Yao) and coastal (She) HM people in the middle Bronze Age period and the latter obtained more gene flow from Ancient Northern East Asians. Multiple admixture models further confirmed that extensive gene flow from surrounding ST, TK, and AN people entangled in forming the gene pool of Chinese coastal HM people. Genetic findings of isolated shared unique ancestral components based on the sharing alleles and haplotypes deconstructed that HM people from the Yungui Plateau carried the breadth of previously unknown genomic diversity. We identified a direct and recent genetic connection between Chinese inland and Southeast Asian HM people as they shared the most extended identity-by-descent fragments, supporting the long-distance migration hypothesis. Uniparental phylogenetic topology and network-based phylogenetic relationship reconstruction found ancient uniparental founding lineages in southwestern HM people. Finally, the population-specific biological adaptation study identified the shared and differentiated natural selection signatures among inland and coastal HM people associated with physical features and immune functions. The allele frequency spectrum of cancer susceptibility alleles and pharmacogenomic genes showed significant differences between HM and northern Chinese people. CONCLUSIONS: Our extensive genetic evidence combined with the historical documents supported the view that ancient HM people originated from the Yungui regions associated with ancient "Three-Miao tribes" descended from the ancient Daxi-Qujialing-Shijiahe people. Then, some have recently migrated rapidly to Southeast Asia, and some have migrated eastward and mixed respectively with Southeast Asian indigenes, Liangzhu-related coastal ancient populations, and incoming southward ST people. Generally, complex population migration, admixture, and adaptation history contributed to the complicated patterns of population structure of geographically diverse HM people.

Distinguished biological adaptation architecture aggravated population differentiation of Tibeto-Burman-speaking people.

Tibeto-Burman (TB) people have endeavored to adapt to the hypoxic, cold, and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic period. However, the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people, as well as their interaction mechanism, remain unknown. Here, we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity, admixture history, and differentiated adaptative features of geographically different TB-speaking people. We identify genetic differentiation related to geography and language among TB-speaking people, consistent with their differentiated admixture process with incoming or indigenous ancestral source populations. A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin hypothesis. We finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish speakers. Adaptative signatures associated with the physical pigmentation (EDAR and SLC24A5) and metabolism (ALDH9A1) are identified in Loloish people, which differed from the high-altitude adaptative genetic architecture in Tibetan. TB-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.

Sex-dependent association of DNA methylation in the coding region of the corticotropin-releasing hormone gene and schizophrenia spectrum disorder.

BACKGROUND: Schizophrenia spectrum disorder (SSD) is a common mental disorder causing severe and chronic disability. Epigenetic changes in genes related to the hypothalamic-pituitary-adrenal (HPA) axis are believed to play an important role in SSD pathogenesis. The methylation status of the corticotropin-releasing hormone (CRH) gene, which is central to the HPA axis, has not been investigated in patients with SSD. AIM: We investigated the methylation status of the coding region of the CRH gene (hereafter, CRH methylation) using peripheral blood samples from patients with SSD. SUBJECTS AND METHODS: We used sodium bisulphite and MethylTarget to determine CRH methylation after collecting peripheral blood samples from 70 patients with SSD who had positive symptoms and 68 healthy controls. RESULTS: CRH methylation was significantly increased in patients with SSD, especially in male patients. CONCLUSIONS: Differences in CRH methylation were detectable in the peripheral blood of patients with SSD. Epigenetic abnormalities in the CRH gene were closely related to positive symptoms of SSD, suggesting that epigenetic processes may mediate the pathophysiology of SSD.

Cytotoxicity of 4 Wild Mushrooms in a Case of Yunnan Sudden Unexplained Death.

OBJECTIVES: To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD. METHODS: Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope. RESULTS: Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts. CONCLUSIONS: The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.

Whole exome sequencing with a focus on cardiac disease-associated genes in families of sudden unexplained deaths in Yunnan, southwest of China.

OBJECTIVES: To explore the causes of sudden unexpected death (SUD) and to search for high-risk people, whole exome sequencing (WES) was performed in families with SUDs.  METHODS: Whole exome sequencing of 25 people from 14 SUD families were screened based on cardiac disease-associated gene variants, and their echocardiograms and electrocardiograms (ECG) were also examined. The protein function of mutated genes was predicted by SIFT, PolyPhen2 and Mutation Assessor. RESULTS: In the group of 25 people from 14 SUD families, 49 single nucleotide variants (SNVs) of cardiac disease-associated genes were found and verified by Sanger sequencing. 29 SNVs of 14 cardiac disorder-related genes were predicted as pathogens by software. Among them, 7 SNVs carried by two or more members were found in 5 families, including SCN5A (c.3577C > T), IRX4 (c.230A > G), LDB3 (c.2104 T > G), MYH6 (c.3G > A), MYH6 (c.3928 T > C), TTN (c.80987C > T) and TTN (c.8069C > T). 25 ECGs were collected. In summary, 4 people had J-point elevation, 2 people had long QT syndrome (LQTS), 4 people had prolonged QT interval, 3 people had T-wave changes, 3 people had sinus tachycardia, 4 people had sinus bradycardia, 4 people had left side of QRS electrical axis, and 3 people had P wave broadening. Echocardiographic results showed that 1 person had atrial septal defect, 1 person had tricuspid regurgitation, and 2 people had left ventricular diastolic dysfunction. CONCLUSIONS: Of the 14 heart disease-associated genes in 14 SUDs families, there are 7 possible pathological SNVS may be associated with SUDs. Our results indicate that people with ECG abnormalities, such as prolonged QT interval, ST segment changes, T-wave change and carrying the above 7 SNVs, should be the focus of prevention of sudden death.

Comprehensive Understanding the Forensic Systematic Effectiveness in Chinese Yunnan Hani Group and Intercontinental Population Architecture Differentiation Analyses via a Novel Set of Autosomal InDel Markers.

BACKGROUND: Chinese Yunnan Hani group is an East Asian ethnic group mainly distributed in China, Thailand, Laos, Vietnam, and Burma. The genetic makeup of Chinese Yunnan Hani ethnic group remains to be further investigated. The insertion/deletion (InDel) polymorphism genetic markers are highlighted by their merits such as shorter amplified fragments, lower mutation rates, and are considered effective tools for population genetic investigations. METHODS: The 221 individuals of Chinese Yunnan Hani group were enrolled to obtain the genetic data and polymorphic profiles of 57 autosomal InDels through multiplex amplification and genotyping. Population genetic analyses were performed between Chinese Yunnan Hani group and 30 global reference populations. RESULTS: The forensic parameters, especially cumulative power of discrimination and combined probability of exclusion values, which were 0.9999999999999999999999968 and 0.999958, separately, illustrated that this novel InDel multiplex amplification system could be utilized as a powerful tool for personal identification and paternity testing in Chinese Yunnan Hani group. The results of population genetic analyses indicated that Chinese Yunnan Hani group showed relatively smaller genetic distances and similar genetic structures with the reference East Asian populations. CONCLUSIONS: The genetic polymorphisms and results of intercontinental population architecture differentiation analyses demonstrated the high efficiency of this novel InDel multiplex amplification system. The genomic data and findings of this research will contribute to the ongoing genetic exploration of Chinese Yunnan Hani group and increase our insights into the genetic architecture of worldwide populations.

Forensic Characteristics and Genetic Background Dissections of Chinese Manchu and Zhuang Groups Using 59 Autosomal Diallelic InDels and 2 miniSTRs.

BACKGROUND: The latest development in molecular biology has offered an opportunity to construct multiplex panel with better applicability for forensic purpose, and a self-developed 64-plex panel, including 59 autosomal diallelic InDels, 2 miniSTRs, 2 Y-InDels, and an Amelogenin gene, was validated to be an effective forensic tool in the previous study. METHODS: By applying the 64-plex panel for DNA profiling, the obtained genotypes and the corresponding frequency data were used to investigate the forensic characteristics and population genetic structures of the Chinese Manchu group from the Inner Mongolia Autonomous Region and the Chinese Zhuang group from the Yunnan province. RESULTS: The 64-plex panel was qualified to perform human identification and paternity testing with the combined powers of discrimination of 0.99999999999999999999999999758 and 0.99999999999999999999999999691; and cumulative probabilities of exclusion of 0.99999866 and 0.99999880 in the studied Manchu and Zhuang groups, respectively. Relatively closer genetic relationships were found between the Chinese Manchu group and Han population in Beijing; and between the Chinese Zhuang group and Vietnamese Kinh population. CONCLUSIONS: It could be indicated from the results that, with the preliminary ability to distinguish ancestral components from all the studied groups, the 64-plex panel can not only serve as a robust forensic panel in the Manchu and Zhuang groups, but also offer genetic insights into the genetic differentiations and substructures of these populations.

Genetic polymorphisms of 16 X-STR loci in the Hani population from Southwest China.

X chromosomal short tandem repeats (X-STRs) have the characteristics of both autosomal and uniparental genetic markers and have been shown to be particularly useful in forensic casework. However, relevant research or reports have not focused on X-STRs in the Hani population. To investigate the genetic variation and forensic efficiency of 16 X-STR loci in the Hani ethnic minority, we calculated the allele frequencies and forensic parameters of 451 (116 males and 335 females) unrelated healthy Hani individuals from Yunnan Province, Southwest China. All these loci are highly polymorphic in Hani individuals in Yunnan Province except DXS6800. The combined power of discrimination in males (PDM) and power of discrimination in females (PDF) were found to be 0.999 999 998 433 993 and 0.999 999 999 999 998, respectively. Furthermore, a population genetic structure investigation between the Yunnan Hani population and another 18 populations was performed using a principal component analysis, multidimensional scaling plot and neighbouring-joining phylogenetic tree and the findings illustrated that neighbouring populations and different nationalities in the same area appeared to have a closer evolutionary relationship. This study provides the first batch of X chromosome genetic polymorphism data of the Hani population in Yunnan Province, Southwest China and enriches the reference database of the Chinese minority population.Key pointsThis is the first study of X-STR in the Hani population.We calculated the allele frequencies and forensic parameters of 451 unrelated healthy Hani individuals from Yunnan Province, Southwest China.All these loci are highly polymorphic in Hani individuals in Yunnan Province except DXS6800.The genetic relationship between the Hani and other 18 nationalities was analyzed.This study provides the first batch of X chromosome genetic polymorphism data of the Hani population in Yunnan Province, Southwest China and enriches the reference database of the Chinese minority population.

Forensic efficacy evaluation and genetic structure exploration of the Yunnan Miao group by a multiplex InDel panel.

The aim of the study was to better understand the genetic characteristics of the Miao group in China. Herein, genetic characteristics and forensic application values of 57 autosomal insertion-deletion (InDel) loci were investigated in 210 unrelated healthy individuals from the Chinese Yunnan Miao (YM) group. Meanwhile, the genetic differences in these InDels were compared among the YM group and 26 reference populations. The results of forensic statistical analyses showed that all 57 autosomal InDels were in accordance with the Hardy-Weinberg and linkage equilibria of pairwise loci in the Chinese YM group. Moreover, the combined probability of discrimination and probability of exclusion in the YM group were 0.9999999999999999999999801 and 0.999928, respectively, which indicated that the multiplex amplification including 57 autosomal InDels was suitable for forensic individual identification and paternity testing in the Chinese YM group. In addition, the results of allelic frequency distribution differential analyses, principal component analyses, phylogenetic tree reconstruction, and genetic structure analyses between the Chinese YM group and 26 reference populations revealed that the genetic similarities between the YM group and East Asian populations were more than that between the YM group and other geographical populations. This 57 autosomal InDels system can also effectively distinguish East Asian, European, and African populations.

Insights into AIM-InDel diversities in Yunnan Miao and Hani ethnic groups of China for forensic and population genetic purposes.

BACKGROUND: Ancestry informative markers are regarded as useful tools for inferring the ancestral information of an individual, which have been widely used in the criminal investigations and population genetic studies. Previously, a multiplex amplification panel containing 39 AIM-InDel loci was constructed. This study aims to investigate the genetic polymorphisms of these 39 AIM-InDel loci in Yunnan Hani and Miao ethnic groups, and to uncover their genetic affinities with reference populations based on the AIM-InDel markers. MATERIALS AND METHODS: In this research, 39 AIM-InDel profiles of 203 unrelated Miao individuals and 203 unrelated Hani individuals in Yunnan province of China were acquired. Additionally, we evaluated the genetic polymorphisms of 39 InDel loci in Yunnan Miao and Hani groups. Moreover, the genetic relationships among Yunnan Miao, Hani and reference populations were also clarified based on Nei's genetic distances, pairwise fixation indexes, principal component analyses, phylogenetic analyses, and STRUCTURE analyses. RESULTS: Genetic diversity analyses demonstrated that these InDel loci showed varying degrees of genetic polymorphisms, and could be utilized in forensic identifications in Yunnan Miao and Hani groups. The results of principal component analyses, phylogenetic analyses and Structure analyses revealed that Yunnan Miao and Hani groups had closer genetic relationships with East Asian populations, especially with the populations from Southern China. This research enriched the genetic data of Chinese ethnic minority, and provided ancestral information of Yunnan Miao and Hani groups from the perspective of population genetics.

Genetic polymorphisms of 16 X-STR loci analyzed in the Han population of Yunnan Province, Southwest China.

To investigate the genetic diversity and forensic identification efficiency of X-chromosomal short tandem repeats (X-STRs) in the Yunnan Han population, 16 X-STRs in 415 Yunnan Han individuals (247 males and 168 females) were studied. A total of 137 alleles were detected, and all loci in the Yunnan Han population were highly polymorphic. The combined discrimination of males (PDm) and females (PDf) was 0.9999997769115 and 0.999999999999999999996, respectively. Interpopulation comparisons between the Yunnan Han population and 21 other populations showed that the evolutionary relationships between different groups with the same ethnic group or nearby geographic origins were closer. This study provides the first data on X-STR genetic polymorphisms in the Yunnan Han population and enriches the X-STR database for the Chinese Han population.

Genetic polymorphism investigation of 16 X-STR loci in the Bai ethnic minority in Yunnan Province, Southwest China.

To investigate the genetic variation and forensic efficiency of 16 X-chromosomal short tandem repeat (X-STR) loci (DX6795, DXS9902, DXS8378, HPRTB, GATA165B12, DXS7132, DXS7424, DXS6807, DXS6803, GATA172D05, DXS6800, DXS10134, GATA31E08, DXS10159, DXS6789, and DXS6810) in the Bai minority, we calculated allele frequencies, forensic parameters, and haplotype frequencies in 424 (202 males and 222 females) unrelated, healthy Bai individuals from Dali Bai Autonomous Prefecture in Yunnan Province, China. We observed a total of 132 alleles; 5-19 alleles were detected in each locus, and the corresponding allele frequencies ranged from 0.0016 to 0.7589. All of the loci detected were highly polymorphic in the Bai population in Yunnan Province, except DXS6800. The values for the combined power of discrimination in females (PDf) and males (PDm) were 0.999999999999996 and 0.999999997487061, respectively. According to a phylogenetic tree, neighboring populations and different nationalities in the same area appeared to have relatively close evolutionary relationships. This study provides and complements X-chromosome genetic polymorphism data for the Bai people in Yunnan Province, Southwest China, and enriches the available reference materials for this Chinese minority population.

Sex-dependent DNA hypermethylation of SLC6A4 in patients with schizophrenia.

Schizophrenia (SCZ) is a mental health condition with a complex pathogenic mechanism. One important hypothesis of SCZ pathology is serotonin (5-HT) impairment, and the 5-HT transporter, encoded by the SLC6A4 gene, plays a key role in regulating 5-HT levels. Some studies have confirmed that the CpG island upstream of exon 1 and the island shore region of SLC6A4 are hypermethylated in SCZ; however, to the best of our knowledge, there has been no study on the methylation level of CpG islands downstream of SLC6A4 exon 1. Methylation of CpG islands downstream of SLC6A4 exon 1 was measured in the peripheral blood of SCZ patients with positive symptoms using the MethylTarget method. Overall, the methylation level of SLC6A4 was significantly higher in women than in men. In intergroup comparisons, the level of SLC6A4 methylation was higher in the SCZ group than in the control group, especially within the male subgroup. Moreover, methylation levels of several CpG sites correlated significantly with SCZ. These results suggest that epigenetic alterations of SLC6A4 are related to SCZ pathophysiology. These findings improve the current understanding of the role of the 5-HT system in the pathological development of SCZ.

Forensic efficiencies of individual identification, kinship testing and ancestral inference in three Yunnan groups based on a self-developed multiple DIP panel.

Deletion/insertion polymorphism (DIP), as a short insertion/deletion sequence polymorphic genetic marker, has attracted the attention of forensic genetic scientist due to its lack of stutter, short amplicon and abundant ancestral information. In this study, based on a self-developed 43 autosomal deletion/insertion polymorphism (A-DIP) loci panel which could meet the forensic application purposes of individual identification, kinship testing and ancestral inference to some extent, we evaluated the forensic efficiencies of the above three forensic objectives in Chinese Yi, Hani and Miao groups of Yunnan province. The cumulative match probability (CPM) and combined probability of exclusion (CPE) of these three groups were 1.11433E-18, 8.24299E-19, 4.21721E-18; 0.999610217, 0.999629285 and 0.999582084, respectively. Average 96.65% full sibling pairs could be identified from unrelated individual pairs (as likelihood ratios > 1) using this DIP panel, whereas the average false positive rate was 3.69% in three target Yunnan groups. With the biogeographical ancestor prediction models constructed by extreme gradient boosting (XGBoost) and support vector machine (SVM) algorithms, 0.8239 (95% CI 0.7984, 0.8474) of the unrelated individuals could be correctly divided according to the continental origins based on the 43 A-DIPs which were large frequency distribution differentiations among different continental populations. The present results of principal component analysis (PCA), multidimensional scaling (MDS), neighbor joining (NJ) and maximum likelihood (ML) phylogenetic trees and STRUCTURE analyses indicated that these three Yunnan groups had relatively close genetic distances with East Asian populations.

Forensic genetic polymorphisms of 16 X-STR loci in the Yunnan Miao population and their relationship to other Chinese groups.

Allele frequencies for 16 X-chromosomal STR (X-STR) loci were obtained from a sample set of 440 unrelated Yunnan Miao individuals in China. A total of 117 alleles were observed in this group, with allele frequencies ranging from 0.0016 to 0.7565. The most informative marker for the studied population was DXS10134, with a polymorphism information content (PIC) of 0.8499, and the least polymorphic locus was DXS6810 (PIC = 0.3071). The power of discrimination (PD) varied from 0.4046 (DXS6800) to 0.8642 (DXS10134) in males and from 0.6188 (DXS6800) to 0.9673 (DXS10134) in females. The combined PDM and PDF were 0.999999989975990 and 0.999999999999949, respectively. The combined MECD and MECT were 0.999983301904059 and 0.999999915883733, respectively. Furthermore, population genetic structure investigation between the Yunnan Miao and 20 other populations using principal component analysis (PCA), multidimensional scaling plot (MDS), and neighboring-joining (NJ) phylogenetic tree analyses illustrated significant genetic difference between the Yunnan Miao and the other populations. This study is the first to provide X chromosome genetic polymorphism data of the Miao population in Yunnan Province and can be used as a supplementary reference to enrich the national database.