The Role of Noncoding RNAs in Brain Cells during Rat Cerebral Ischemia

Ischemic brain stroke is one of the most serious and socially important medical conditions. Transcriptome analysis is a prospective approach to the study of the mechanisms of brain functioning, both under normal conditions and in ischemia. In addition to mRNA encoding proteins, the study of noncoding RNAs in ischemia has exceptional importance for the development of new strategies for neuroprotection. Of greatest interest are microRNAs (miRNAs) and circular RNAs (circRNAs). circRNAs have a closed structure and predominantly brain-specific expression. They can interact with miRNAs, diminish their activity, and thereby inhibit miRNA-mediated repression of mRNA. Recently, it has become clear that the analysis of circRNA-miRNA-mRNA interactions is an important requirement for the detailed study of the mechanisms of damage and regeneration during ischemia. This chapter reviews the most recent data on the role of circRNAs, miRNAs, mRNAs, and their interactions in brain cells under normal conditions and in cerebral ischemia

Ethnic Differences in Susceptibility to the Effects of Platinum- Based Chemotherapy

There is substantial interindividual variability in the efficacy and tolerability of anticancer drugs. Such differences can be greater between individuals of different ethnicities. The clinical studies demonstrate that individuals from Asia (East Asia) are more susceptible to the effects of platinum-containing chemotherapies than their Western counterparts. To determine whether population-related genomics (i.e., frequencies of DNA polymorphisms) contribute to differences in patient outcomes, polymorphisms in 109 genes involved mainly in xenobiotic metabolism, DNA repair, the cell cycle, and apoptosis were tested in Russian (Caucasians) and Yakut (North Asians) ovarian cancer patients receiving cisplatin-based chemotherapy. Totally, 232 polymorphisms were genotyped in individual DNA samples using conventional PCR and arrayed primer extension technology. Single nucleotide polymorphisms (SNPs) in more than 30 genes were found to be associated with one or more of clinical end points (i.e., tumor response, progression-free survival, overall survival, and side effects). However, all associations between SNPs and clinical outcomes were specific for each of ethnic group studied. These findings let us to propose the existence of distinctive ethnic-related characteristics in molecular mechanisms determining the sensitivity of patients to platinum drug effects

Population Genetics of Latvians in the Context of Admixture between North-Eastern European Ethnic Groups

Publisher Copyright: © 2018 Astrida Krumiņa et al., published by Sciendo.This article presents a review on population genetics of Latvians, which alongside Lithuanians are the two extant Baltic speaking populations. The article provides a description of genome-wide single nucleotide polymorphism (SNP) data and contains a comparative analysis of the results of studies performed on classical autosomal genetic markers, mitochondrial DNA (mtDNA) and the non-recombining part of the Y chromosome (NRY), with data on neighbouring populations. The study also covers data of recently performed ancient DNA (aDNA) studies carried out on samples from the territory of today's Latvia. The results of population genetic studies have shown a mixture of eastern and western genetic traits in present-day Latvians with only small differences between Latvian subpopulations. Studies of the Baltic "tribal gene" LWb, as well as the gene's SERPINA1 allele PIZ have indicated the presence of a considerable Baltic admixture in the neighbouring Finno-Ugric and Slavic populations. Although mtDNA analyses have shown that Latvians genetically in general belong to the same common gene pool as most of the Europeans, the Y-chromosomal lineage composition suggests that they are most similar to Northern and Eastern European populations of Lithuanians, Estonians, and Eastern-Slavic populations, which are ethnogenetically closest to them. The analysis of aDNA from the Early and Middle Neolithic did not present any genomic evidence of gene-flow from Central European farmers or any mitochondrial or Y-chromosomal haplogroups that are typical for them in the hunter-gatherers from the territory of today's Latvia and Lithuania.publishersversionPeer reviewe

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

A Genome-Wide Analysis of Populations from European Russia Reveals a New Pole of Genetic Diversity in Northern Europe

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No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe