Genome-wide sequence analyses of ethnic populations across Russia

The Russian Federation is the largest and one of the most ethnically diverse countries in the world, however no centralized reference database of genetic variation exists to date. Such data are crucial for medical genetics and essential for studying population history. The Genome Russia Project aims at filling this gap by performing whole genome sequencing and analysis of peoples of the Russian Federation. Here we report the characterization of genome-wide variation of 264 healthy adults, including 60 newly sequenced samples. People of Russia carry known and novel genetic variants of adaptive, clinical and functional consequence that in many cases show allele frequency divergence from neighboring populations. Population genetics analyses revealed six phylogeographic partitions among indigenous ethnicities corresponding to their geographic locales. This study presents a characterization of population-specific genomic variation in Russia with results important for medical genetics and for understanding the dynamic population history of the world's largest country

The Complex Admixture History and Recent Southern Origins of Siberian Populations

International audienceAlthough Siberia was inhabited by modern humans at an early stage, there is still debate over whether it remained habitable during the extreme cold of the Last Glacial Maximum or whether it was subsequently repopulated by peoples with recent shared ancestry. Previous studies of the genetic history of Siberian populations were hampered by the extensive admixture that appears to have taken place among these populations, because commonly used methods assume a tree-like population history and at most single admixture events. Here we analyze geogenetic maps and use other approaches to distinguish the effects of shared ancestry from prehistoric migrations and contact, and develop a new method based on the covariance of ancestry components, to investigate the potentially complex admixture history. We furthermore adapt a previously devised method of admixture dating for use with multiple events of gene flow, and apply these methods to whole-genome genotype data from over 500 individuals belonging to 20 different Siberian ethnolinguistic groups. The results of these analyses indicate that there have been multiple layers of admixture detectable in most of the Siberian populations, with considerable differences in the admixture histories of individual populations. Furthermore, most of the populations of Siberia included here, even those settled far to the north, appear to have a southern origin, with the northward expansions of different populations possibly being driven partly by the advent of pastoralism, especially reindeer domestication. These newly developed methods to analyze multiple admixture events should aid in the investigation of similarly complex population histories elsewhere

The Complex Admixture History and Recent Southern Origins of Siberian Populations

International audienceAlthough Siberia was inhabited by modern humans at an early stage, there is still debate over whether it remained habitable during the extreme cold of the Last Glacial Maximum or whether it was subsequently repopulated by peoples with recent shared ancestry. Previous studies of the genetic history of Siberian populations were hampered by the extensive admixture that appears to have taken place among these populations, because commonly used methods assume a tree-like population history and at most single admixture events. Here we analyze geogenetic maps and use other approaches to distinguish the effects of shared ancestry from prehistoric migrations and contact, and develop a new method based on the covariance of ancestry components, to investigate the potentially complex admixture history. We furthermore adapt a previously devised method of admixture dating for use with multiple events of gene flow, and apply these methods to whole-genome genotype data from over 500 individuals belonging to 20 different Siberian ethnolinguistic groups. The results of these analyses indicate that there have been multiple layers of admixture detectable in most of the Siberian populations, with considerable differences in the admixture histories of individual populations. Furthermore, most of the populations of Siberia included here, even those settled far to the north, appear to have a southern origin, with the northward expansions of different populations possibly being driven partly by the advent of pastoralism, especially reindeer domestication. These newly developed methods to analyze multiple admixture events should aid in the investigation of similarly complex population histories elsewhere

Investigating the prehistory of Tungusic peoples of Siberia and the Amur-Ussuri region with complete mtDNA genome sequences and Y-chromosomal markers.

Evenks and Evens, Tungusic-speaking reindeer herders and hunter-gatherers, are spread over a wide area of northern Asia, whereas their linguistic relatives the Udegey, sedentary fishermen and hunter-gatherers, are settled to the south of the lower Amur River. The prehistory and relationships of these Tungusic peoples are as yet poorly investigated, especially with respect to their interactions with neighbouring populations. In this study, we analyse over 500 complete mtDNA genome sequences from nine different Evenk and even subgroups as well as their geographic neighbours from Siberia and their linguistic relatives the Udegey from the Amur-Ussuri region in order to investigate the prehistory of the Tungusic populations. These data are supplemented with analyses of Y-chromosomal haplogroups and STR haplotypes in the Evenks, Evens, and neighbouring Siberian populations. We demonstrate that whereas the North Tungusic Evenks and Evens show evidence of shared ancestry both in the maternal and in the paternal line, this signal has been attenuated by genetic drift and differential gene flow with neighbouring populations, with isolation by distance further shaping the maternal genepool of the Evens. The Udegey, in contrast, appear quite divergent from their linguistic relatives in the maternal line, with a mtDNA haplogroup composition characteristic of populations of the Amur-Ussuri region. Nevertheless, they show affinities with the Evenks, indicating that they might be the result of admixture between local Amur-Ussuri populations and Tungusic populations from the north

Neuroimaging in chronic Viliuisk encephalomyelitis (VE).

<p>(<b>A,B</b>) Representative magnetic resonance imaging (MRI) of mild (<b>A</b>) and severe (<b>B</b>) chronic VE showing severity-dependent enlargement of the lateral and third ventricles. Shown are transaxial FLAIR, coronar T1w and sagittal T2w images demonstrating ventricular enlargement including the 3^rd ventricle, periventricular hyperintense signal, thinning of the corpus callosum, but normal cortical and infratentorial structures. The extent of these changes correlated to disease severity. (<b>C</b>) Semi-quantitative measurement of ventricular volume in VE patients compared to Yakutian and age- and sex-matched Caucasian controls (see Supporting Information online for technical details). As an estimate of ventricular volumes, the sums of normalized ventricular areas from all slices showing ventricles obtained with a standardized acquisition protocol are displayed (bars and crosses are mean values ± SD). # indicates <i>P<</i>0.0001 when compared to all other groups (ANOVA with post-hoc <i>t</i>-test including Bonferroni correction). (<b>D</b>) Representative pneumoencephalography of subacute VE showing ventricular enlargement (arrows indicate enlarged “bloated” lateral ventricles) and absent air filling of the subarachnoidal spaces of the hemispheric convexities (arrowheads indicate the stops of air filling), suggestive for arachnoideal adhesions.</p

CSF results in VE patients and controls.

<p>Data are number of patients (%) with pathological results, or mean±SD (range).</p><p>Fisher's exact test for comparison of pathological vs. normal results did not reveal significant differences between both groups for all parameters.</p><p>OCIBs, oligoclonal IgG bands; AI, antibody index.</p

Neuropathology in subacute Viliuisk encephalomyelitis (VE).

<p>(<b>A</b>) Representative brain histology microphotograph for all three available VE brain samples showed massive intraparenchymal and meningeal infiltrations (Giemsa and DAPI staining confirmed, not shown). (<b>B</b>) Anti-ECP immunohistochemistry proved increased appearance of eosinophilic leucocytes. Scale bar, 100 µm.</p

Communicating Hydrocephalus Following Eosinophilic Meningitis Is Pathogenic for Chronic Viliuisk Encephalomyelitis in Northeastern Siberia

<div><p>Background</p><p>Viliuisk encephalomyelitis (VE) is an endemic neurological disease in Northeast Siberia and generally considered to be a chronic encephalomyelitis of unknown origin actually spreading in the Sakha (Yakutian) Republic.</p><p>Methodology and Principle Findings</p><p>In search for the pathophysiology and causative agent of VE, we performed a cross-sectional study on clinical, serological and neuroimaging data on chronic VE patients during two medical expeditions to three villages within the Viliuiski river basin in the Republic of Sakha in 2000 and to the capital Yakutsk in 2006. The severity of the core clinical picture with predominant sensory ataxia, gait apraxia, lower limb spasticity, cognitive impairment and bladder dysfunction correlated with the degree of MRI findings showing enlargement of inner ventricular spaces as in communicating hydrocephalus. Laboratory studies revealed transient eosinophilia during the preceding acute meningitis-like phase, but no ongoing inflammatory process in the CSF. We found immune reactions against <i>Toxocara canis</i> in the majority of chronic VE patients but rarely in controls (<i>P</i> = 0.025; Fisher's exact test). Histological analysis of subacute to subchronic VE brain samples showed eosinophilic infiltrations with no signs of persistent <i>Toxocara canis</i> infection.</p><p>Conclusions and Significance</p><p>Our data showed that pressure by the communicating hydrocephalus as a mechanical factor is the major pathogenic mechanism in chronic VE, most likely triggered by eosinophilic meningitis. There are no signs for an ongoing inflammatory process in chronic VE. The past eosinophilic reaction in VE might be caused by <i>Toxocara</i> ssp. infection and might therefore represent the first hint for an initial cause leading to the development of chronic VE. Our data provide a framework for future studies and potential therapeutic interventions for this enigmatic epidemic neurological disease potentially spreading in Sakha Republic.</p></div

Immunoreactivity against organisms associated with eosinophilic meningitis in patients with VE and controls.

$<p>Relative risks and 95% confidence interval (CI) for comparison of pathological results vs. normal results.</p>Δ<p>Fisher's exact test for comparison of pathological results vs. normal results.</p>a<p>Normal results for all tests are: Not detectable.</p