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

Genomic analyses inform on migration events during the peopling of Eurasia.

High-coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.Support was provided by: Estonian Research Infrastructure Roadmap grant no 3.2.0304.11-0312; Australian Research Council Discovery grants (DP110102635 and DP140101405) (D.M.L., M.W. and E.W.); Danish National Research Foundation; the Lundbeck Foundation and KU2016 (E.W.); ERC Starting Investigator grant (FP7 - 261213) (T.K.); Estonian Research Council grant PUT766 (G.C. and M.K.); EU European Regional Development Fund through the Centre of Excellence in Genomics to Estonian Biocentre (R.V.; M.Me. and A.Me.), and Centre of Excellence for Genomics and Translational Medicine Project No. 2014-2020.4.01.15-0012 to EGC of UT (A.Me.) and EBC (M.Me.); Estonian Institutional Research grant IUT24-1 (L.S., M.J., A.K., B.Y., K.T., C.B.M., Le.S., H.Sa., S.L., D.M.B., E.M., R.V., G.H., M.K., G.C., T.K. and M.Me.) and IUT20-60 (A.Me.); French Ministry of Foreign and European Affairs and French ANR grant number ANR-14-CE31-0013-01 (F.-X.R.); Gates Cambridge Trust Funding (E.J.); ICG SB RAS (No. VI.58.1.1) (D.V.L.); Leverhulme Programme grant no. RP2011-R-045 (A.B.M., P.G. and M.G.T.); Ministry of Education and Science of Russia; Project 6.656.2014/K (S.A.F.); NEFREX grant funded by the European Union (People Marie Curie Actions; International Research Staff Exchange Scheme; call FP7-PEOPLE-2012-IRSES-number 318979) (M.Me., G.H. and M.K.); NIH grants 5DP1ES022577 05, 1R01DK104339-01, and 1R01GM113657-01 (S.Tis.); Russian Foundation for Basic Research (grant N 14-06-00180a) (M.G.); Russian Foundation for Basic Research; grant 16-04-00890 (O.B. and E.B); Russian Science Foundation grant 14-14-00827 (O.B.); The Russian Foundation for Basic Research (14-04-00725-a), The Russian Humanitarian Scientific Foundation (13-11-02014) and the Program of the Basic Research of the RAS Presidium “Biological diversity” (E.K.K.); Wellcome Trust and Royal Society grant WT104125AIA & the Bristol Advanced Computing Research Centre (http://www.bris.ac.uk/acrc/) (D.J.L.); Wellcome Trust grant 098051 (Q.A.; C.T.-S. and Y.X.); Wellcome Trust Senior Research Fellowship grant 100719/Z/12/Z (M.G.T.); Young Explorers Grant from the National Geographic Society (8900-11) (C.A.E.); ERC Consolidator Grant 647787 ‘LocalAdaptatio’ (A.Ma.); Program of the RAS Presidium “Basic research for the development of the Russian Arctic” (B.M.); Russian Foundation for Basic Research grant 16-06-00303 (E.B.); a Rutherford Fellowship (RDF-10-MAU-001) from the Royal Society of New Zealand (M.P.C.)

The gene pool of Belgorod oblast population : Study of biochemical gene markers in populations of Ukraine and Belarus and the position of the Belgorod population in the Eastern Slavic gene pool system

The characteristics of the gene pools of indigenous populations of Ukraine and Belarus have been studied using 28 alleles of 10 loci of biochemical gene markers (HP, GC, TF, PI, C'3, ACP1, GLO1, PGM1, ESD, and 6-PGD). The gene pools of the Russian and Ukrainian indigenous populations of Belgorod oblast (Russia) and the indigenous populations of Ukraine and Belarus have been comparedyesBS

The gene pool of Belgorod oblast population : Study of biochemical gene markers in populations of Ukraine and Belarus and the position of the Belgorod population in the Eastern Slavic gene pool system

yesBSUThe characteristics of the gene pools of indigenous populations of Ukraine and Belarus have been studied using 28 alleles of 10 loci of biochemical gene markers (HP, GC, TF, PI, C'3, ACP1, GLO1, PGM1, ESD, and 6-PGD). The gene pools of the Russian and Ukrainian indigenous populations of Belgorod oblast (Russia) and the indigenous populations of Ukraine and Belarus have been compare

Adiponectin gene single-nucleotide polymorphisms in patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease

Background. It is generally believed that environmental and genetic factors interact with the formation of nonalcoholic fatty liver disease (NAFLD) phenotype and determine its progression. Both NAFLD and type 2 diabetes (T2D) are heterogeneous diseases with common pathogenic pathways. Adiponectin is an adipokine, which increases the sensitivity of hepatocytes and muscle to insulin, modulates energy homeostasis, glucose/lipid metabolism, and inflammatory response. A number of significant adiponectin gene polymorphisms are known in this area. The purpose of the study was to evaluate the possible association between two adiponectin gene (ADIPOQ) variants, +276 G/T (rs1501299) and –11391 G/A (rs17300539), and susceptibility to NAFLD in T2D patients of Ukrainian population. Materials and methods. Case-control study included a total of 155 persons with T2D (males/females: 77/78, age 54.55 ± 0.73 years, T2D duration 6.66 ± 0.49 years, body mass index 32.20 ± 0.43 kg/m2, waist/hip circumference 0.98 ± 0.01 m, HbA1c 7.26 ± 0.11 %) for biochemical characteristics (lipid profile, non-esterified fatty acids (NEFA), insulin, total adiponectin, etc.), including 90 T2D patients with NAFLD, 245 — with rs1501299 genotyping, 155 — with rs17300539 genotyping, and 51 sex and age-matched control subjects. The +276 G/T and –11391 G/A were determined by polymerase chain reaction — restriction fragment length polymorphism method with endonucleases Mva1269I (BsmI) and MspI (HpaII). Insulin resistance (IR) was assessed using homeostasis model assessment (HOMA) algorithm and as adipose IR (Adipo-IR, NEFAxinsulin). Unpaired Student’s t test, c2 test and Spearman’s rank order were used. To predict the probabilities of genetic risk in NAFLD, the odds ratio (OR) and 95% confidence interval (CI) were calculated. Results. T2D patients were characterized by overweight and obesity, which were more significant in the presence of NAFLD (p < 0.01). It was accompanied by an increase in НОМА-IR (p < 0.05) and triglycerides (p < 0.001) levels. We found that Adipo-IR was higher in patients with T2D as compared to the controls (p < 0.001), and this index was significantly increased in T2D patients with NAFLD in contrast to obesity-matched persons without NAFLD (190.18 ± 22.15 vs 133.32 ± 13.58 mmol/L·pmol/L, p < 0.02), with negative correlation between Adipo-IR and adiponectin level in T2D patients with NAFLD only (rs = –0.350, p = 0.021). Stratification of non-NAFLD patients by +276G/T genotype suggests the prevalence of GT- and TT-genotypes. Thus, the rs1501299 G-allele increased the risk of NAFLD in comparison with T-allele (OR = 4.44, 95% CI = 2.89–6.81, p < 0.05). We also found a significant difference in the frequency of –11391G/A between T2D and control groups, but not between the patients with and without NAFLD. We observed that the haplotype of GT/GG had been more common in T2D with NAFLD, and twice less often detected in patients without hepatic disease (33 and 16.49 %, respectively, p < 0.05). Conclusions. We can recommend Adipo-IR index as a predictive marker for the NAFLD development and the indicator for therapy success in T2D patients. We established new genetic markers (rs1501299 G-allele, rs17300539 and rs1501299 GG/GG and GT/GG haplotypes, respectively) for the risk of NAFLD development in T2D patients

A recent bottleneck of Y chromosome diversity coincides with a global change in culture

Contains fulltext : 153022.pdf (publisher's version ) (Open Access)It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males