Lessons from the Whole Exome Sequencing Effort in Populations of Russia and Tajikistan

© 2016, Springer Science+Business Media New York.In contrast with the traditional methods applied to assessment of population diversity, high-throughput sequencing technologies have a wider application in clinical practice with greater potential to find novel disease-causing variants for multifactorial disorders. Widely used test panels may not meet their goal to diagnose the patient’s condition with a full reliability since this method often does not take into account the population frequencies of analyzed genetic markers. Here, we analyzed 57 male individuals of five ethnic groups from Russia and Tajikistan using the whole exome sequencing technique (Ion AmpliSeq Exome), which resulted in detecting more than 299,000 single nucleotide polymorphisms. Samples formed clusters on the PCA plot according to the geographical location of the corresponding populations. Thereby, the methodology of whole-exome sequencing, in general, and the Ion AmpliSeq Exome panel, in particular, could be positively applied for the purposes of population genetics and for detection of the novel clinically relevant variants

Reconstructing the genetic structure of the Kazakh from clan distribution data

Applying quasigenetic markers - non-biological traits which are nevertheless inherited in generations - is one of the research fields within human population genetics. For the West European, East European, and Caucasus populations, surnames are typical quasigenetic markers. For Central Asian populations, particularly Kazakh, the clan affiliation serves as a good marker: a set of papers demonstrated that many clans include mainly persons which biologically descent from a recent common ancestor. In this study, we analyzed a large (~4.2 million persons) dataset on quasigenetic markers - the geographic distribution of 50 Kazakh clans at the beginning of the 20th century, and compared the dataset with the direct data of the Y-chro-mosomal diversity in modern Kazakh populations. The analysis included three steps: the isonymy method, which is standard for quasigenetic markers, comparing frequencies of quasigenetic markers, and comparing the quasigenetic and genetic datasets. We constructed 50 maps of frequency of the distribution of each clan and revealed that these maps correlate with the maps of genetic distances. The Mantel test also demonstrated a significant correlation between geographic and quasigenetic distances (г = 0.60; p < 0.05). The analysis of inter-population variability revealed the largest diversity between geographic territories corresponding to the social-territorial groups of the Kazakh Khanate (zhuzes) rather than to other historical groups that existed on the territory of Kazakhstan in preceding and modern epochs. The same is evidenced by the principal components and multidimensional scaling plots, which grouped geographic populations into three clusters corresponding to three zhuzes. This indicates that the final structuring of the Kazakh gene pool might have occurred during the Kazakh Khanate period

The genetic history of admixture across inner Eurasia

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this record.Data Availability. Genome-wide sequence data of two Botai individuals (BAM format) are available at the European Nucleotide Archive under the accession number PRJEB31152 (ERP113669). Eigenstrat format array genotype data of 763 present-day individuals and 1240K pulldown genotype data of two ancient Botai individuals are available at the Edmond data repository of the Max Planck Society (https://edmond.mpdl.mpg.de/imeji/collection/Aoh9c69DscnxSNjm?q=).The indigenous populations of inner Eurasia, a huge geographic region covering the central Eurasian steppe and the northern Eurasian taiga and tundra, harbor tremendous diversity in their genes, cultures and languages. In this study, we report novel genome-wide data for 763 individuals from Armenia, Georgia, Kazakhstan, Moldova, Mongolia, Russia, Tajikistan, Ukraine, and Uzbekistan. We furthermore report additional damage-reduced genome-wide data of two previously published individuals from the Eneolithic Botai culture in Kazakhstan (~5,400 BP). We find that present-day inner Eurasian populations are structured into three distinct admixture clines stretching between various western and eastern Eurasian ancestries, mirroring geography. The Botai and more recent ancient genomes from Siberia show a decrease in contribution from so-called “ancient North Eurasian” ancestry over time, detectable only in the northern-most “forest-tundra” cline. The intermediate “steppe-forest” cline descends from the Late Bronze Age steppe ancestries, while the “southern steppe” cline further to the South shows a strong West/South Asian influence. Ancient genomes suggest a northward spread of the southern steppe cline in Central Asia during the first millennium BC. Finally, the genetic structure of Caucasus populations highlights a role of the Caucasus Mountains as a barrier to gene flow and suggests a post-Neolithic gene flow into North Caucasus populations from the steppe.Max Planck SocietyEuropean Research Council (ERC)Russian Foundation for Basic Research (RFBR)Russian Scientific FundNational Science FoundationU.S. National Institutes of HealthAllen Discovery CenterUniversity of OstravaCzech Ministry of EducationXiamen UniversityFundamental Research Funds for the Central UniversitiesMES R

Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649)

The MDM2 promoter SNP285C is located on the SNP309G allele. While SNP309G enhances Sp1 transcription factor binding and MDM2 transcription, SNP285C antagonizes Sp1 binding and reduces the risk of breast-, ovary- and endometrial cancer. Assessing SNP285 and 309 genotypes across 25 different ethnic populations (>10.000 individuals), the incidence of SNP285C was 6-8% across European populations except for Finns (1.2%) and Saami (0.3%). The incidence decreased towards the Middle-East and Eastern Russia, and SNP285C was absent among Han Chinese, Mongolians and African Americans. Interhaplotype variation analyses estimated SNP285C to have originated about 14,700 years ago (95% CI: 8,300 - 33,300). Both this estimate and the geographical distribution suggest SNP285C to have arisen after the separation between Caucasians and modern day East Asians (17,000 - 40,000 years ago). We observed a strong inverse correlation (r = -0.805; p < 0.001) between the percentage of SNP309G alleles harboring SNP285C and the MAF for SNP309G itself across different populations suggesting selection and environmental adaptation with respect to MDM2 expression in recent human evolution. In conclusion, we found SNP285C to be a pan-Caucasian variant. Ethnic variation regarding distribution of SNP285C needs to be taken into account when assessing the impact of MDM2 SNPs on cancer risk

The gene pool of the Belgorod oblast population : II. "Family name portraits" in groups of districts with different degrees of subdivision and the role of migrations in their formation

yesBSUThe frequencies and spectra of surnames have been analyzed in groups of raions (districts) of the Belgorod oblast (region) with different degrees of population subdivision. The “family name portraits” of districts with low and moderate inbreeding levels are similar both to each other and to the “family name portrait” of the Belgorod oblast as a whol

The gene pool of the Belgorod oblast population : II. "Family name portraits" in groups of districts with different degrees of subdivision and the role of migrations in their formation

The frequencies and spectra of surnames have been analyzed in groups of raions (districts) of the Belgorod oblast (region) with different degrees of population subdivision. The “family name portraits” of districts with low and moderate inbreeding levels are similar both to each other and to the “family name portrait” of the Belgorod oblast as a wholeyesBS

The gene pool of the Belgorod oblast population : description of the "genetic landscape" of 22 district populations

Data on the frequencies of all (50412) surnames in a total population of 849399 people have been treated by various methods of multivariate statistics (cluster analysis, multidimensional scaling, and factor analysis) to show that 22 district populations of the Central Chernozem region of Russia form a definite, ordered system of population groupsyesBS

The gene pool of the Belgorod oblast population : changes in population genetic relationships during the past 50 years

The model of the Belgorod oblast population has been used to demonstrate different effects of administrative reforms on microevolution in human populations. For the populations that formerly belonged to Kursk oblast, changes in the regional administrative structure have lead to an increase in the genetic distances between themyesBS

The gene pool of the Belgorod oblast population : changes in the endogamy indices of district populations with time

yesBSUChanges in the endogamy indices of district populations of the Central Chernozem region of Russia during the past 100 years were studied. The size of an elementary population in this region increased from that of a rural municipality in the mid-20th century to that of an administrative district in the late 20th centur

The gene pool of the Belgorod oblast population : I. Differentiation of all district populations based on anthroponymic data

The gene pool of the entire population of all the 21 raions (districts) of the Belgorod oblast (region) has been studied using anthroponymic data. Considerable geographic variations of the number of surnames and the degree of population subdivision in the 21 districts have been demonstratedyesBS