Data Harmonization Guidelines to Combine Multi-platform Genomic Data from Admixed Populations and Boost Power in Genome-Wide Association Studies.

Data harmonization involves combining data from multiple independent sources and processing the data to produce one uniform dataset. Merging separate genotypes or whole-genome sequencing datasets has been proposed as a strategy to increase the statistical power of association tests by increasing the effective sample size. However, data harmonization is not a widely adopted strategy due to the difficulties with merging data (including confounding produced by batch effects and population stratification). Detailed data harmonization protocols are scarce and are often conflicting. Moreover, data harmonization protocols that accommodate samples of admixed ancestry are practically non-existent. Existing data harmonization procedures must be modified to ensure the heterogeneous ancestry of admixed individuals is incorporated into additional downstream analyses without confounding results. Here, we propose a set of guidelines for merging multi-platform genetic data from admixed samples that can be adopted by any investigator with elementary bioinformatics experience. We have applied these guidelines to aggregate 1544 tuberculosis (TB) case-control samples from six separate in-house datasets and conducted a genome-wide association study (GWAS) of TB susceptibility. The GWAS performed on the merged dataset had improved power over analyzing the datasets individually and produced summary statistics free from bias introduced by batch effects and population stratification. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Processing separate datasets comprising array genotype data Alternate Protocol 1: Processing separate datasets comprising array genotype and whole-genome sequencing data Alternate Protocol 2: Performing imputation using a local reference panel Basic Protocol 2: Merging separate datasets Basic Protocol 3: Ancestry inference using ADMIXTURE and RFMix Basic Protocol 4: Batch effect correction using pseudo-case-control comparisons.

Assessing the limits of local ancestry inference from small reference panels.

Admixture is a common biological phenomenon among populations of the same or different species. Identifying admixed tracts within individual genomes can provide valuable information to date admixture events, reconstruct ancestry-specific demographic histories, or detect adaptive introgression, genetic incompatibilities, as well as regions of the genomes affected by (associative-) overdominance. Although many local ancestry inference (LAI) methods have been developed in the last decade, their performance was accessed using large reference panels, which are rarely available for non-model organisms or ancient samples. Moreover, the demographic conditions for which LAI becomes unreliable have not been explicitly outlined. Here, we identify the demographic conditions for which local ancestries can be best estimated using very small reference panels. Furthermore, we compare the performance of two LAI methods (RFMix and MOSAIC) with the performance of a newly developed approach (simpLAI) that can be used even when reference populations consist of single individuals. Based on simulations of various demographic models, we also determine the limits of these LAI tools and propose post-painting filtering steps to reduce false-positive rates and improve the precision and accuracy of the inferred admixed tracts. Besides providing a guide for using LAI, our work shows that reasonable inferences can be obtained from a single diploid genome per reference under demographic conditions that are not uncommon among past human groups and non-model organisms.

Investigating the effectiveness of forensic genetics and population genetic diversity using a multi-InDel system in Chinese Hezhou and Southern Shaanxi Han populations.

INTRODUCTION: Multiple insertion-deletion (multi-InDel) has greater potential in forensic genetics than InDel, and its efficacy in kinship testing, individual identification, DNA mixture detection and ancestry inference remains to be explored. METHODS: Consequently, we designed an efficient and robust system consisting of 41 multi-InDels to evaluate its efficacy in forensic applications in Chinese Hezhou Han (HZH) and Southern Shaanxi Han (SNH) populations and explore the genetic relationships between the SNH, HZH, and 26 reference populations. RESULTS AND CONCLUSION: The obtained results showed that 38 out of the 41 multi-InDels had fairly high genetic variations. The the cumulative probability of discrimination and exclusion values of the multi-InDels (except MI38) in HZH and SNH populations both exceeded 1-e-25 and 1-e-6, correspondingly. The genetic compositions of HZH and SNH individuals were similar to that of East Asians and the Naive Bayes model could well distinguish East Asians, Africans and Americans. These results indicated that the multi-InDel systerm can serve as an effective tool to provide important evidence for the development of multi-InDels in forensic practice and better analyse the genetic background of the Han Chinese populations.

A general approach for inferring the ancestry of recent ancestors of an admixed individual.

The genome of an individual from an admixed population consists of segments originated from different ancestral populations. Most existing ancestry inference approaches focus on calling these segments for the extant individual. In this paper, we present a general ancestry inference approach for inferring recent ancestors from an extant genome. Given the genome of an individual from a recently admixed population, our method can estimate the proportions of the genomes of the recent ancestors of this individual that originated from some ancestral populations. The key step of our method is the inference of ancestors (called founders) right after the formation of an admixed population. The inferred founders can then be used to infer the ancestry of recent ancestors of an extant individual. Our method is implemented in a computer program called PedMix2. To the best of our knowledge, there is no existing method that can practically infer ancestors beyond grandparents from an extant individual's genome. Results on both simulated and real data show that PedMix2 performs well in ancestry inference.

Comprehensive landscape of non-CODIS STRs in global populations provides new insights into challenging DNA profiles.

The worldwide implementation of short tandem repeats (STR) profiles in forensic genetics necessitated establishing and expanding the CODIS core loci set to facilitated efficient data management and exchange. Currently, the mainstay CODIS STRs are adopted in most general-purpose forensic kits. However, relying solely on these loci failed to yield satisfactory results for challenging tasks, such as bio-geographical ancestry inference, complex DNA mixture profile interpretation, and distant kinship analysis. In this context, non-CODIS STRs are potent supplements to enhance the systematic discriminating power, particularly when combined with the high-throughput next-generation sequencing (NGS) technique. Nevertheless, comprehensive evaluation on non-CODIS STRs in diverse populations was scarce, hindering their further application in routine caseworks. To address this gap, we investigated genetic variations of 178 historically available non-CODIS STRs from ethnolinguistically different worldwide populations and studied their characteristics and forensic potentials via high-coverage whole genome sequencing (WGS) data. Initially, we delineated the genomic properties of these non-CODIS markers through sequence searching, repeat structure scanning, and manual inspection. Subsequent population genetics analysis suggested that these non-CODIS STRs had comparable polymorphism levels and forensic utility to CODIS STRs. Furthermore, we constructed a theoretical next-generation sequencing (NGS) panel comprising 108 STRs (20 CODIS STRs and 88 non-CODIS STRs), and evaluated its performance in inferring bio-geographical ancestry origins, deconvoluting complex DNA mixtures, and differentiating distant kinships using real and simulated datasets. Our findings demonstrated that incorporating supplementary non-CODIS STRs enabled the extrapolation of multidimensional information from a single STR profile, thereby facilitating the analysis of challenging forensic tasks. In conclusion, this study presents an extensive genomic landscape of forensic non-CODIS STRs among global populations, and emphasized the imperative inclusion of additional polymorphic non-CODIS STRs in future NGS-based forensic systems.

A proof-of-principle study: The potential application of MiniHap biomarkers in ancestry inference based on the QNome nanopore sequencing.

Haplotyped SNPs convey forensic-related information, and microhaplotypes (MHs), as the most representative of this kind of marker, have proved the potential value for human forensics. In recent years, nanopore sequencing technology has developed rapidly, with its outstanding ability to sequence long continuous DNA fragments and obtain phase information, making the detection of longer haplotype marker possible. In this proof-of-principle study, we proposed a new type of forensic marker, MiniHap, based on five or more SNPs within a molecular distance less than 800 bp, and investigated the haplotype data of 56 selected MiniHaps in five Chinese populations using the QNome nanopore sequencing. The sequencing performance, allele (haplotype) frequencies, forensic parameters, effective number of alleles (Ae), and informativeness (In) were subsequently calculated. In addition, we performed principal component analysis (PCA), phylogenetic tree, and structure analysis to investigate the population genetic relationships and ancestry components among the five investigated populations and 26 worldwide populations. MiniHap-04 exhibited remarkable forensic efficacy, with 148 haplotypes reported and the Ae was 66.9268. In addition, the power of discrimination (PD) was 0.9934, the probability of exclusion (PE) was 0.9898, and the In value was 0.7893. Of the 56 loci, 85.71% had PD values above 0.85, 66.07% had PE values above 0.54, 67.86% had Ae values over 7.0%, and 55.36% were with In values above 0.2 across all samples, indicating that most of the MiniHaps are suitable for individual identification, paternity testing, mixture deconvolution, and ancestry inference. Moreover, the results of PCA, phylogenetic tree and structure analysis demonstrated that this MiniHap panel had the competency in continental population ancestry inference, but the differentiation within intracontinental/linguistically restricted subpopulations was not ideal. Such findings suggested that the QNome device for MiniHap detection was feasible and this novel marker has the potential in ancestry inference. Yet, the establishment of a more comprehensive database with sufficient reference population data remains necessary to screen more suitable MiniHaps.

The jigsaw puzzle of pedigree: whole-genome resequencing reveals genetic diversity and ancestral lineage in Sunong black pigs.

The Sunong black pig is a new composite breed under development generated from Chinese indigenous pig breeds (i.e., Taihu and Huai) and intensive pig breeds (i.e., Landrace and Berkshire), which is an important genetic material for studying breeding mechanisms. However, there is currently limited knowledge about the genetic structure and germplasm characteristics of Sunong black pigs. To comprehensively understand their genetic composition and ancestry proportions, we performed population structure and local ancestry inference analysis based on whole-genome sequencing information. The results showed that Sunong black pigs could be clustered independently into a group, whose pedigree was intermediate between indigenous and commercial pig breeds, but closer to commercial pigs. Furthermore, local ancestry inference analysis revealed that Sunong black pigs inherited immune and reproductive traits from indigenous pig breeds, including CC and CXC chemokine family, Toll-like receptor family, IFN gene family, ESR1, AREG and EREG gene, while growth and development-related traits were inherited from commercial pig breeds, including IGF1 and GSY2 gene. Overall, Sunong black pigs have formed a relatively stable genome structure with some advantageous traits inherited from their ancestral breeds. This study deepened the understanding of the breeding mechanism of Sunong black pigs and provided a reference for cross-breeding programmes in livestock.

Ancestral Information Analysis of Chinese Korean Ethnic Group via a Novel Multiplex DIP System.

Deletion/insertion polymorphism (DIP) is one of the more promising genetic markers in the field of forensic genetics for personal identification and biogeographic ancestry inference. In this research, we used an in-house developed ancestry-informative marker-DIP system, including 56 autosomal diallelic DIPs, three Y-chromosomal DIPs, and an Amelogenin gene, to analyze the genetic polymorphism and ancestral composition of the Chinese Korean group, as well as to explore its genetic relationships with the 26 reference populations. The results showed that this novel panel exhibited high genetic polymorphism in the studied Korean group and could be effectively applied for forensic individual identification in the Korean group. In addition, the results of multiple population genetic analyses indicated that the ancestral component of the Korean group was dominated by northern East Asia. Moreover, the Korean group was more closely related to the East Asian populations, especially to the Japanese population in Tokyo. This study enriched the genetic data of the Korean ethnic group in China and provided information on the ancestry of the Korean group from the perspective of population genetics.

Development of an Okinawa panel for biogeographic inference of Okinawans.

BACKGROUND: The Precision ID Ancestry Panel with 165 SNP markers was unable to differentiate between mainland Japanese and Okinawa Japanese or to distinguish either of them from other East Asian populations. AIM: An Okinawa panel was developed with the aim of further separating Okinawa Japanese individuals from mainland Japanese and other Asian groups. Seventy-five SNPs were selected using the most informative markers from the literature. Further, 22 SNPs were selected to separate Okinawa Japanese at minimum SNPs. SUBJECTS AND METHODS: Samples were collected from 48 unrelated individuals from mainland Japan and 46 unrelated residents of the Okinawa prefecture. Data were evaluated by STRUCTURE, principal component, and GenoGeographer analyses. RESULTS: The 22 SNP set had similar levels of differentiation in STRUCTURE and PCA analyses as the 75 SNP set. GenoGeographer analysis showed that, out of the 46 Okinawa Japanese individuals, the 75 SNP and 22 SNP sets correctly assigned the Okinawan population as the most likely population of origin for 32 and 31 individuals, respectively. CONCLUSION: Neither SNP set could completely differentiate between Okinawa Japanese and other Asian groups, however, these sets should be useful for crime investigation, when the sample, cost and time are limited.

Can demographic histories explain long-term isolation and recent pulses of asymmetric gene flow between highly divergent grey fox lineages?

Secondary contact zones between deeply divergent, yet interfertile, lineages provide windows into the speciation process. North American grey foxes (Urocyon cinereoargenteus) are divided into western and eastern lineages that diverged approximately 1 million years ago. These ancient lineages currently hybridize in a relatively narrow zone of contact in the southern Great Plains, a pattern more commonly observed in smaller-bodied taxa, which suggests relatively recent contact after a long period of allopatry. Based on local ancestry inference with whole-genome sequencing (n = 43), we identified two distinct Holocene pulses of admixture. The older pulse (500-3500 YBP) reflected unidirectional gene flow from east to west, whereas the more recent pulse (70-200 YBP) of admixture was bi-directional. Augmented with genotyping-by-sequencing data from 216 additional foxes, demographic analyses indicated that the eastern lineage declined precipitously after divergence, remaining small throughout most of the late Pleistocene, and expanding only during the Holocene. Genetic diversity in the eastern lineage was highest in the southeast and lowest near the contact zone, consistent with a westward expansion. Concordantly, distribution modelling indicated that during their isolation, the most suitable habitat occurred far east of today's contact zone or west of the Great Plains. Thus, long-term isolation was likely caused by the small, distant location of the eastern refugium, with recent contact reflecting a large increase in suitable habitat and corresponding demographic expansion from the eastern refugium. Ultimately, long-term isolation in grey foxes may reflect their specialized bio-climatic niche. This system presents an opportunity for future investigation of potential pre- and post-zygotic isolating mechanisms.

Anthropogenic hybridization and its influence on the adaptive potential of the Sardinian wild boar (Sus scrofa meridionalis).

The wild boar (Sus scrofa meridionalis) arrived in Sardinia with the first human settlers in the early Neolithic with the potential to hybridize with the domestic pig (S. s. domesticus) throughout its evolution on the island. In this paper, we investigated the possible microevolutionary effects of such introgressive hybridization on the present wild boar population, comparing Sardinian wild specimens with several commercial pig breeds and Sardinian local pigs, along with a putatively unadmixed wild boar population from Central Italy, all genotyped with a medium density SNP chip. We first aimed at identifying hybrids in the population using different approaches, then examined genomic regions enriched for domestic alleles in the hybrid group, and finally we applied two methods to find regions under positive selection to possibly highlight instances of domestic adaptive introgression into a wild population. We found three hybrids within the Sardinian sample (3.1% out of the whole dataset). We reported 11 significant windows under positive selection with a method that looks for overly differentiated loci in the target population, compared with other two populations. We also identified 82 genomic regions with signs of selection in the domestic pig but not in the wild boar, two of which overlapped with genomic regions enriched for domestic alleles in the hybrid pool. Genes in these regions can be linked with reproductive success. Given our results, domestic introgression does not seem to be pervasive in the Sardinian wild boar. Nevertheless, we suggest monitoring the possible spread of advantageous domestic alleles in the coming years.

Exploration of the ancestral inference effectiveness of 126 AI-SNPs and the genetic feature of Inner Mongolian Manchu group.

In addition to the validated ancestry-informative single nucleotide polymorphisms (AI-SNPs) in classic panels, there are many new potential AI-SNPs yet to be explored. Moreover, the search for AI-SNPs with highly discriminative power for ancestry inference in inter- and intra-continental populations has become a realistic need. In this study, 126 novel AI-SNPs were selected to distinguish the African, European, Central/South Asian and East Asian populations, and a random forest model was introduced to assess the performance of the AI-SNP set. This panel was further used in the genetic analysis of the Manchu group in Inner Mongolia, China, based on 79 reference populations from seven continental regions. Results showed that the 126 AI-SNPs were able to achieve the ancestry informative inference for African, East Asian, European, and Central/South Asian populations. Population genetic analyses indicated that the Manchu group in Inner Mongolia was genetically typical of East Asian populations and was more closely related to the northern Han Chinese and Japanese than to other Altaic-speaking populations. Overall, this study provided a selection of new promising loci of ancestry inference for major intercontinental populations and intracontinental subgroups, as well as genetic insights and valuable data for dissecting the genetic structure of the Inner Mongolian Manchu group.

A self-developed AIM-InDel panel designed for degraded DNA analysis: Forensic application characterization and genetic landscape investigation in the Han Chinese population.

To assist in forensic DNA investigation, we developed a new panel capable of simultaneously amplifying 56 ancestry-informative InDels, three Y-InDels and the Amelogenin locus in one PCR reaction. The fragment lengths of the InDel amplicons in this panel were restricted to <200 bp to benefit degraded DNA analysis. In this study, we explored the efficiency of this new panel for forensic applications in the Han Chinese population, and further shed light on the genetic structures of Han populations. We showed that the new panel could be served as an efficient tool for ancestry inference of intercontinental populations. Especially, the Han individuals in different regions could be 100% correctly predicted to be of East Asian origin with this new panel. The Han populations in different regions shared similar ancestry components in their genetic structures. Besides, we also revealed that the new panle could be useful for individual identification in different Han Chinese populations. In conclusion, we have provided the necessary evidence that the self-constructed new panel could play an important role in forensic DNA investigation.

Forensic biogeographical ancestry inference: recent insights and current trends.

BACKGROUND: As a powerful complement to the paradigmatic DNA profiling strategy, biogeographical ancestry inference (BGAI) plays a significant part in human forensic investigation especially when a database hit or eyewitness testimony are not available. It indicates one's biogeographical profile based on known population-specific genetic variations, and thus is crucial for guiding authority investigations to find unknown individuals. Forensic biogeographical ancestry testing exploits much of the recent advances in the understanding of human genomic variation and improving of molecular biology. OBJECTIVE: In this review, recent development of prospective ancestry informative markers (AIMs) and the statistical approaches of inferring biogeographic ancestry from AIMs are elucidated and discussed. METHODS: We highlight the research progress of three potential AIMs (i.e., single nucleotide polymorphisms, microhaplotypes, and Y or mtDNA uniparental markers) and discuss the prospects and challenges of two methods that are commonly used in BGAI. CONCLUSION: While BGAI for forensic purposes has been thriving in recent years, important challenges, such as ethics and responsibilities, data completeness, and ununified standards for evaluation, remain for the use of biogeographical ancestry information in human forensic investigations. To address these issues and fully realize the value of BGAI in forensic investigation, efforts should be made not only by labs/institutions around the world independently, but also by inter-lab/institution collaborations.

Genome-Wide Admixture Mapping Identifies Wild Ancestry-of-Origin Segments in Cultivated Robusta Coffee.

Humans have had a major influence on the dissemination of crops beyond their native range, thereby offering new hybridization opportunities. Characterizing admixed genomes with mosaic origins generates valuable insight into the adaptive history of crops and the impact on current varietal diversity. We applied the ELAI tool-an efficient local ancestry inference method based on a two-layer hidden Markov model to track segments of wild origin in cultivated accessions in the case of multiway admixtures. Source populations-which may actually be limited and partially admixed-must be generally specified when using such inference models. We thus developed a framework to identify local ancestry with admixed source populations. Using sequencing data for wild and cultivated Coffea canephora (commonly called Robusta), our approach was found to be highly efficient and accurate on simulated hybrids. Application of the method to assess elite Robusta varieties from Vietnam led to the identification of an accession derived from a likely backcross between two genetic groups from the Congo Basin and the western coastal region of Central Africa. Admixtures resulting from crop hybridization and diffusion could thus lead to the generation of elite high-yielding varieties. Our methods should be widely applicable to gain insight into the role of hybridization during plant and animal evolutionary history.

Systematically exploring the performance of a self-developed Multi-InDel system in forensic identification, ancestry inference and genetic structure analysis of Chinese Manchu and Mongolian groups.

The insertion/deletion (InDel) polymorphism has promising applications in forensic DNA analysis. However, the insufficient forensic efficiencies of the present InDel-based systems restrict their applications in parentage testing, due to the lower genetic polymorphism of the biallelic InDel locus and the limited number of InDel loci in a multiplex amplification system. Here, we introduced an in-house developed system which contained 41 polymorphic Multi-InDel markers (equivalent to 82 InDels in total), to serve as an efficient and reliable tool for different forensic applications in the Manchu and Mongolian groups. We demonstrated that the new system exhibited potential efficiencies for personal identification, parentage testing, two-person DNA mixture interpretation and ancestry inference of intercontinental populations. Meanwhile, we explored the genetic backgrounds of the Manchu and Mongolian groups by conducting a series of population genetic analyses. We showed that the Manchu and Mongolian groups shared closer genetic relationships with East Asian populations, especially Han Chinese populations in northern China. Moreover, more similar genetic compositions were detected between the Manchu group and the northern Han populations in this study, suggesting that the Manchu group had higher genetic affinities with northern Han populations than the Mongolian group. Overall. this study provided the necessary evidence that these Multi-InDel genetic markers could play an important role in forensic applications.

Multiple founding paternal lineages inferred from the newly-developed 639-plex Y-SNP panel suggested the complex admixture and migration history of Chinese people.

BACKGROUND: Non-recombining regions of the Y-chromosome recorded the evolutionary traces of male human populations and are inherited haplotype-dependently and male-specifically. Recent whole Y-chromosome sequencing studies have identified previously unrecognized population divergence, expansion and admixture processes, which promotes a better understanding and application of the observed patterns of Y-chromosome genetic diversity. RESULTS: Here, we developed one highest-resolution Y-chromosome single nucleotide polymorphism (Y-SNP) panel targeted for uniparental genealogy reconstruction and paternal biogeographical ancestry inference, which included 639 phylogenetically informative SNPs. We genotyped these loci in 1033 Chinese male individuals from 33 ethnolinguistically diverse populations and identified 256 terminal Y-chromosomal lineages with frequency ranging from 0.0010 (singleton) to 0.0687. We identified six dominant common founding lineages associated with different ethnolinguistic backgrounds, which included O2a2b1a1a1a1a1a1a1-M6539, O2a1b1a1a1a1a1a1-F17, O2a2b1a1a1a1a1b1a1b-MF15397, O2a2b2a1b1-A16609, O1b1a1a1a1b2a1a1-F2517, and O2a2b1a1a1a1a1a1-F155. The AMOVA and nucleotide diversity estimates revealed considerable differences and high genetic diversity among ethnolinguistically different populations. We constructed one representative phylogenetic tree among 33 studied populations based on the haplogroup frequency spectrum and sequence variations. Clustering patterns in principal component analysis and multidimensional scaling results showed a genetic differentiation between Tai-Kadai-speaking Li, Mongolic-speaking Mongolian, and other Sinitic-speaking Han Chinese populations. Phylogenetic topology inferred from the BEAST and Network relationships reconstructed from the popART further showed the founding lineages from culturally/linguistically diverse populations, such as C2a/C2b was dominant in Mongolian people and O1a/O1b was dominant in island Li people. We also identified many lineages shared by more than two ethnolinguistically different populations with a high proportion, suggesting their extensive admixture and migration history. CONCLUSIONS: Our findings indicated that our developed high-resolution Y-SNP panel included major dominant Y-lineages of Chinese populations from different ethnic groups and geographical regions, which can be used as the primary and powerful tool for forensic practice. We should emphasize the necessity and importance of whole sequencing of more ethnolinguistically different populations, which can help identify more unrecognized population-specific variations for the promotion of Y-chromosome-based forensic applications.

Fast, accurate local ancestry inference with FLARE.

Local ancestry is the source ancestry at each point in the genome of an admixed individual. Inferred local ancestry is used for admixture mapping and population genetic analyses. We present FLARE (fast local ancestry estimation), a method for local ancestry inference. FLARE achieves high accuracy through the use of an extended Li and Stephens model, and it achieves exceptional computational performance through incorporation of computational techniques developed for genotype imputation. Memory requirements are reduced through on-the-fly compression of reference haplotypes and stored checkpoints. Computation time is reduced through the use of composite reference haplotypes. These techniques allow FLARE to scale to datasets with hundreds of thousands of sequenced individuals and to provide superior accuracy on large-scale data. FLARE is open source and available at https://github.com/browning-lab/flare.

Inferring bio-geographical ancestry with 35 microhaplotypes.

During the past decades, with the blooming of large-scale human genetic studies, we are beginning to understand how bio-geographical information could be reflected by genetic variations. And the technological advance in massively parallel sequencing gives advantages to some novel forensic markers such as microhaplotype (BIM). In the present study, we selected and characterized 35 novel bio-geographical informative BIMs based on the 1000 Genomes Project (1KG). All loci had short lengths less than 100 bp, high effective allele numbers (Ae) from 1.875 to 3.980 with an average of 2.798, and high informativeness (In) value from 0.701 to 0.865 with an average of 0.748, which indicates the 35 BIMs possessed great discriminating power. Using these 35 BIMs, the individuals from 1KG could be successfully differentiated into five supergroups defined by 1KG (AFR, AMR, EAS, EUR, and SAS). We also included some individuals from the Simons Genome Diversity Project (SGDP) for further validation. As a result, most individuals could be accurately predicted except for those from super-populations that do not exist in 1KG dataset. In conclusion, the present novel 35 BIMs could be a useful tool for bio-geographical ancestry inference.

A sequence-based 163plex microhaplotype assay for forensic DNA analysis.

Novel genetic marker microhaplotype has led to an upsurge in forensic genetic research. This study established a 163 microhaplotype (MH) multiplex assay based on next-generation sequencing (NGS) and evaluated the assay's performance and applicability. Our results showed that the 163 MH assay was accurate, repeatable and reliable, and could distinguish between African, European-American, Southern Asia and Eastern Asia populations. Among the 163 MH makers, 48 MHs with Ae > 3.0 in China Eastern Han were selected and confirmed to be highly polymorphic, with a combined power of discrimination of 1-8.26 × 10-44 and the combined power of exclusion in duos and trios of 1-1.26 × 10-8 and 1-8.27 × 10-16, respectively. Moreover, the mixture study demonstrated the realizability of the MHs in deconvoluting mixtures with different proportions of two to five-person. In conclusion, our findings support the use of this MH assay for ancestry inference, human identification, paternity testing and mixture deconvolution in forensic research.