A Machine-Learning-Based Approach to Prediction of Biogeographic Ancestry within Europe.

Data obtained with the use of massive parallel sequencing (MPS) can be valuable in population genetics studies. In particular, such data harbor the potential for distinguishing samples from different populations, especially from those coming from adjacent populations of common origin. Machine learning (ML) techniques seem to be especially well suited for analyzing large datasets obtained using MPS. The Slavic populations constitute about a third of the population of Europe and inhabit a large area of the continent, while being relatively closely related in population genetics terms. In this proof-of-concept study, various ML techniques were used to classify DNA samples from Slavic and non-Slavic individuals. The primary objective of this study was to empirically evaluate the feasibility of discerning the genetic provenance of individuals of Slavic descent who exhibit genetic similarity, with the overarching goal of categorizing DNA specimens derived from diverse Slavic population representatives. Raw sequencing data were pre-processed, to obtain a 1200 character-long binary vector. A total of three classifiers were used-Random Forest, Support Vector Machine (SVM), and XGBoost. The most-promising results were obtained using SVM with a linear kernel, with 99.9% accuracy and F1-scores of 0.9846-1.000 for all classes.

An association between copy number variation of enhancer involved in craniofacial development and biogeographic ancestry.

Human facial morphology is a combination of many complex traits and is determined by a large number of genes and enhancers. Here, we report a Copy Number Variation (CNV) study of enhancer hs1431 in populations of Central European and South Siberian ancestry. Central European samples included 97 Poles, while South Siberian samples included 78 Buryats and 27 Tuvinians. CNVs were detected by real-time PCR, using ViiA™ 7 Real-Time PCR System (Applied Biosystems). We revealed significant differences in CNV of hs1431 enhancer between Polish and Buryat population (p=0.0378), but not between Central European and South Siberian population (p=0.1225). Our results suggest that an increase in copy number variation of hs1431 enhancer is associated with biogeographic ancestry. However, this result needs extending and replicating in larger cohorts. This is the first study revealing the presence of copy number variation of enhancer hs1431 in humans.

Verification of insertion-deletion markers (InDels) and microsatellites (STRs) as subsidiary tools for inferring Slavic population ancestry.

Genetic markers for the prediction of biogeographical ancestry have proved to be effective tools for law enforcement agencies for many years now. In this study, we attempted to assess the potential of insertion-deletion markers (InDel) and microsatellites (STRs) as subsidiary polymorphisms for inference of Slavic population ancestry. For that purpose, we genotyped Slavic-speaking populations samples from Belarus, the Czech Republic, Poland, Serbia, Ukraine and Russia in 46 InDels and 15 STRs by PCR and capillary electrophoresis and analyzed for between-population differentiation with the use of distance-based methods (FST, principal component analysis and multidimensional scaling). Additionally, we studied a sample from a Polish individual of well-documented genealogy whose biogeographic ancestry had previously been inferred by commercial genomic services using autosomal single nucleotide polymorphisms (SNPs), mitochondrial DNA and Y-SNP markers. For comparative purposes, we used genotype data collected in the "forInDel" browser and allele frequencies from previously published papers. The results obtained for InDels and STRs show that the Slavic populations constitute a genetically homogeneous group, with the exception of the Czechs differing clearly from the other tested populations. The analysis of the known Polish sample in the Snipper application proves the usefulness of the InDel markers on the continental level only. Conversely, microsatellites not only improve prediction, but are also informative if considered as an independent set of ancestry markers.

Simple and cost-effective 14-loci SNP assay designed for differentiation of European, East Asian and African samples.

During every criminal investigation, it is vital to extract as much information as possible from every piece of evidence. When it comes to DNA testing, simple short tandem repeat (STR) typing may soon become a relic because it is now possible to genotype more characteristics. Ancestry informative markers are receiving attention from the forensic community because individuals can be assigned to their population or territory of origin based on their analysis. Many panels of this kind have been proposed so far, yet most of them require typing of a large number of loci. In many cases it is crucial to pick a minimal set of the most informative markers due to the limited amount of material available for analysis. In this study, we demonstrate that 14 carefully picked SNPs combined in two multiplex assays are capable of fast, robust and cost effective three-way differentiation of East Asians, Europeans and Africans.

Genome-wide analysis of cold adaptation in indigenous Siberian populations.

Following the dispersal out of Africa, where hominins evolved in warm environments for millions of years, our species has colonised different climate zones of the world, including high latitudes and cold environments. The extent to which human habitation in (sub-)Arctic regions has been enabled by cultural buffering, short-term acclimatization and genetic adaptations is not clearly understood. Present day indigenous populations of Siberia show a number of phenotypic features, such as increased basal metabolic rate, low serum lipid levels and increased blood pressure that have been attributed to adaptation to the extreme cold climate. In this study we introduce a dataset of 200 individuals from ten indigenous Siberian populations that were genotyped for 730,525 SNPs across the genome to identify genes and non-coding regions that have undergone unusually rapid allele frequency and long-range haplotype homozygosity change in the recent past. At least three distinct population clusters could be identified among the Siberians, each of which showed a number of unique signals of selection. A region on chromosome 11 (chr11:66-69 Mb) contained the largest amount of clustering of significant signals and also the strongest signals in all the different selection tests performed. We present a list of candidate cold adaption genes that showed significant signals of positive selection with our strongest signals associated with genes involved in energy regulation and metabolism (CPT1A, LRP5, THADA) and vascular smooth muscle contraction (PRKG1). By employing a new method that paints phased chromosome chunks by their ancestry we distinguish local Siberian-specific long-range haplotype signals from those introduced by admixture.

Developing STR databases on structured populations: the native South Siberian population versus the Russian population.

Developing a forensic DNA database on a population that consists of local ethnic groups separated by physical and cultural barriers is questionable as it can be genetically subdivided. On the other side, small sizes of ethnic groups, especially in alpine regions where they are sub-structured further into small villages, prevent collecting a large sample from each ethnic group. For such situations, we suggest to obtain both a total population database on allele frequencies across ethnic groups and a list of theta-values between the groups and the total data. We have genotyped 558 individuals from the native population of South Siberia, consisting of nine ethnic groups, at 17 autosomal STR loci of the kit packages AmpFlSTR SGM Plus i, Cyrillic AmpFlSTR Profiler Plus. The groups differentiate from each other with average theta-values of around 1.1%, and some reach up to three to four percent at certain loci. There exists between-village differentiation as well. Therefore, a database for the population of South Siberia is composed of data on allele frequencies in the pool of ethnic groups and data on theta-values that indicate variation in allele frequencies across the groups. Comparison to additional data on northeastern Asia (the Chukchi and Koryak) shows that differentiation in allele frequencies among small groups that are separated by large geographic distance can be even greater. In contrast, populations of Russians that live in large cities of the European part of Russia are homogeneous in allele frequencies, despite large geographic distance between them, and thus can be described by a database on allele frequencies alone, without any specific information on theta-values.

Complex interactions of the Eastern and Western Slavic populations with other European groups as revealed by mitochondrial DNA analysis.

Mitochondrial DNA sequence variation was examined by the control region sequencing (HVS I and HVS II) and RFLP analysis of haplogroup-diagnostic coding region sites in 570 individuals from four regional populations of Poles and two Russian groups from northwestern part of the country. Additionally, sequences of complete mitochondrial genomes representing K1a1b1a subclade in Polish and Polish Roma populations have been determined. Haplogroup frequency patterns revealed in Poles and Russians are similar to those characteristic of other Europeans. However, there are several features of Slavic mtDNA pools seen on the level of regional populations which are helpful in the understanding of complex interactions of the Eastern and Western Slavic populations with other European groups. One of the most important is the presence of subhaplogroups U5b1b1, D5, Z1 and U8a with simultaneous scarcity of haplogroup K in populations of northwestern Russia suggesting the participation of Finno-Ugrian tribes in the formation of mtDNA pools of Russians from this region. The results of genetic structure analyses suggest that Russians from Velikii Novgorod area (northwestern Russia) and Poles from Suwalszczyzna (northeastern Poland) differ from all remaining Polish and Russian samples. Simultaneously, northwestern Russians and northeastern Poles bear some similarities to Baltic (Latvians) and Finno-Ugrian groups (Estonians) of northeastern Europe, especially on the level of U5 haplogroup frequencies. The occurrence of K1a1b1a subcluster in Poles and Polish Roma is one of the first direct proofs of the presence of Ashkenazi-specific mtDNA lineages in non-Jewish European populations.

Optimization of the Y831C mutation detection in human DNA polymerase gamma by allelic discrimination assay.

Many well-defined mutations in the gene for the catalytic subunit of polymerase gamma (POLG1) have been found to be associated with disease, whereas the status of several mutations remains unresolved due to the conflicting reports on their frequencies in populations of healthy individuals. Here, we have developed a highly sensitive, real-time allelic discrimination assay enabling detection of the Y831C mutation in the POLG1 gene. The Y831C mutation is present in the Polish population at a frequency of 2.25%. The new assay is well suited to both extensive population studies and molecular diagnostics of POLG1.

Complete mitochondrial genome and phylogeny of Pleistocene mammoth Mammuthus primigenius.

Phylogenetic relationships between the extinct woolly mammoth (Mammuthus primigenius), and the Asian (Elephas maximus) and African savanna (Loxodonta africana) elephants remain unresolved. Here, we report the sequence of the complete mitochondrial genome (16,842 base pairs) of a woolly mammoth extracted from permafrost-preserved remains from the Pleistocene epoch--the oldest mitochondrial genome sequence determined to date. We demonstrate that well-preserved mitochondrial genome fragments, as long as approximately 1,600-1700 base pairs, can be retrieved from pre-Holocene remains of an extinct species. Phylogenetic reconstruction of the Elephantinae clade suggests that M. primigenius and E. maximus are sister species that diverged soon after their common ancestor split from the L. africana lineage. Low nucleotide diversity found between independently determined mitochondrial genomic sequences of woolly mammoths separated geographically and in time suggests that north-eastern Siberia was occupied by a relatively homogeneous population of M. primigenius throughout the late Pleistocene.

Mitochondrial DNA variability in the Czech population, with application to the ethnic history of Slavs.

Mitochondrial DNA (mtDNA) variability was studied in a sample of 179 individuals representing the Czech population of Western Bohemia. Sequencing of two hypervariable segments, HVS I and HVS II, in combination with screening of coding-region haplogroup-specific RFLP markers revealed that most Czech mtDNAs belong to the common West Eurasian mitochondrial haplogroups (H, pre-V HV*, J, T, U, N1, W, and X). However, about 3% of Czech mtDNAs encompass East Eurasian lineages (A, N9a, D4, M*). A comparative analysis with published data showed that different Slavonic populations in Central and Eastern Europe contain small but marked amounts of East Eurasian mtDNAs. We suggest that the presence of East Eurasian mtDNA haplotypes is not an original feature of the gene pool of the proto-Slavs but rather may be mostly a consequence of admixture with Central Asian nomadic tribes, who migrated into Central and Eastern Europe in the early Middle Ages.