Estonian Biocenter

Tartu, Estonia

Estonian Biocenter

Tartu, Estonia
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Sankovski E.,Estonian Biocenter | Mannik A.,Icosagen Cell Factory OU | Geimanen J.,University of Tartu | Ustav E.,Estonian Biocenter | And 4 more authors.
Journal of Virology | Year: 2014

Betapapillomavirus replication and transcription have not been studied in detail because of a lack of suitable cellular systems supporting human papillomavirus (HPV) genome replication. We have recently shown that the human osteosarcoma cell line U2OS provides a useful environment for the genome replication of many different HPVs, including the betapapillomaviruses HPV5 and HPV8. Using mutational analysis and complementation assay, we demonstrated herein that the viral early proteins E1 and E2 are viral transfactors that are necessary and sufficient for HPV5 genome replication. We also identified four HPV5 early promoter regions with transcription start sites (TSSs) at nucleotides (nt) 184/191, 460, 840, and 1254, respectively, and the HPV late promoter with a TSS at nt 7640. In addition, we mapped the HPV5 early polyadenylation cleavage sites via 3' rapid amplification of cDNA ends (3'RACE) to nt 4457 and 4475. In total, 14 different viral mRNA species, originating from the HPV5 genome, were mapped in U2OS cells during transient and stable replication. The main splicing donor and acceptor sites identified herein are consistent with the data previously obtained in HPV5-positive skin lesions. In addition, we identified novel E8 open reading frame (ORF)-containing transcripts (E8^E1C and E8^E2C) expressed from the HPV5 genome. Similar to several other papillomaviruses, the product of the E8^E2C mRNA acts as a repressor of viral genome replication. © 2014, American Society for Microbiology.

Balanovsky O.P.,Russian Academy of Medical Sciences | Koshel S.M.,Moscow State University | Pshenichnov A.S.,Russian Academy of Medical Sciences | Frolova S.A.,Russian Academy of Medical Sciences | And 9 more authors.
Russian Journal of Genetics | Year: 2011

Yu. P. Altukhov suggested that heterozygosity is an indicator of the state of the gene pool. The idea and a linked concept of genetic ecological monitoring were applied to a new dataset on mtDNA variation in East European ethnic groups. Haplotype diversity (an analog of the average heterozygosity) was shown to gradually decrease northwards. Since a similar trend is known for population density, interlinked changes were assumed for a set of parameters, which were ordered to form a causative chain: latitude increases, land productivity decreases, population density decreases, effective population size decreases, isolation of subpopulations increases, genetic drift increases, and mtDNA haplotype diversity decreases. An increase in genetic drift increases the random inbreeding rate and, consequently, the genetic load. This was confirmed by a significant correlation observed between the incidence of autosomal recessive hereditary diseases and mtDNA haplotype diversity. Based on the findings, mtDNA was assumed to provide an informative genetic system for genetic ecological monitoring; e. g., analyzing the ecology-driven changes in the gene pool. © 2011 Pleiades Publishing, Ltd.

Stolk L.,Erasmus University Rotterdam | Stolk L.,Netherlands Consortium of Healthy Aging | Perry J.R.B.,University of Exeter | Perry J.R.B.,University of Oxford | And 225 more authors.
Nature Genetics | Year: 2012

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 - 10 g8). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-I °B signaling and mitochondrial dysfunction as biological processes related to timing of menopause. © 2012 Nature America, Inc. All rights reserved.

Ellinor P.T.,Massachusetts General Hospital | Lunetta K.L.,Boston University | Lunetta K.L.,Lung and Blood Institutes Framingham Heart Study | Glazer N.L.,University of Washington | And 86 more authors.
Nature Genetics | Year: 2010

Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 × 10 12), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40-1.64; P = 1.83 × 10 21). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization. © 2010 Nature America, Inc. All rights reserved.

Utevska O.M.,University of Kharkiv | Pshenichnov A.S.,Research Center for Medical Genetics | Dibirova K.D.,Research Center for Medical Genetics | Rootsi S.,Estonian Biocenter | And 5 more authors.
Cytology and Genetics | Year: 2015

Results from studying Y-chromosomal polymorphisms of Russian and Ukrainian populations are presented for Slobozhanshina, which is a contemporary border region, inhabited in the 17th–18th centuries at the “Wild Field” boundary due to migrations of both the Russians from the north and Ukrainians from the west. In general, the Ukrainian and Russian populations of Slobozhanshchina are very close genetically; their set and frequency range of Y-chromosome haplogroups are typical for Eastern Europe. However, a detailed analysis of highly informative Y-chromosome markers showed that both nations retain the ethnic specificity of their gene pools after 3.5 centuries of coexistence in the same historical territory: the Ukrainian populations are similar to the rest of Ukraine, and Russian populations gravitate towards the south of European Russia. The persistent genetic differences may be due to the spatial characteristics of marriage migration and the predominant ethnic environment. © 2015, Allerton Press, Inc.

The indigenous inhabitants of the Andaman Islands were considered by many early anthropologists to be pristine examples of a "negrito" substrate of humanity that existed throughout Southeast Asia. Despite over 150 years of research and study, questions over the extent of shared ancestry between Andaman Islanders and other small-bodied, gracile, dark-skinned populations throughout the region are still unresolved. This shared phenotype could be a product of shared history, evolutionary convergence, or a mixture of both. Recent population genetic studies have tended to emphasize long-term physical isolation of the Andaman Islanders and an affinity to ancestral populations of South Asia. We reexamine the genetic evidence from genome-wide autosomal single-nucleotide polymorphism (SNP) data for a shared history between the tribes of Little Andaman (Onge) and Great Andaman, and between these two groups and the rest of South and Southeast Asia (both negrito and non-negrito groups). © 2013 Wayne State University Press.

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