Polymorphism rs652438 of gene <i>mmp12</i> and oxidative DNA damage in bronchial asthma: An experimental non-randomised study

Background. Personalised medicine is an avenue to create technologies for individual prognosis of the disease onset and development. The identification of individual gene haplotypes is prerequisite to detecting predispositions to multifactorial diseases. The level of serum 8-oxoguanine is an indicator of genotoxic stress underlying many pathologies.Objectives. A study of associations of mmp12 gene’s polymorphic variant rs652438 and the nature of genome oxidative damage in bronchial asthma.Methods. Genotyping of polymorphic variant rs652438 of gene mmp12 was performed using TaqMan-probe real-time PCR assays. The gene variant association with disease was assessed by odds ratio. The degree of DNA oxidative damage was estimated by 8-oxoguanine serum concentrations determined in monoclonal antibody-based enzyme immunoassays. The StatPro software package with StatTools (Palisade Corporation, USA) was used for statistical data processing.Results. The haplotype and allele frequencies were established for polymorphic locus rs652438 of the mmp12 gene in the control and bronchial asthma cohorts. Heterozygotes were shown to differ significantly; the estimate was 2.3-fold higher in the control vs. bronchial asthma (BA) cohort (p &lt; 0.05). The AA and GG haplotype frequencies did not differ significantly. The minor allele G odds ratio (OR = 0.362, CI 95% 0.134–0.975) suggests its protective effect. This may be associated with a lowering activity of the encoded macrophage metalloelastase enzyme, which results in a poorer extracellular matrix destruction in the bronchial tree. The baseline 8-oxoG levels in the control and BA samples were 6.4 and 9.4 ng/mL, respectively (U = 25, Ucut-off = 23; p &gt;0.05). An in vitro electromagnetic exposure of varying frequency leads to a significant oxidative genomic damage in both cohorts and an earlier reparative depletion in bronchial asthma vs. control.Conclusion. A protective effect of minor allele G against pathology has been demonstrated. Adaptations to oxidative genomic stress in bronchial asthma manifest by an impaired resistance to in vitro high-intensity electromagnetic exposures

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

Is Spatial Distribution of the HIV-1-resistant CCR5Delta32 Allele Formed by Ecological Factors?

yesBSUIt has been proposed that the D 32 mutation in the chemokine receptor gene, inducing resistance to HIV-1 and, probably, to other virus infections, has undergone selection in historical times. The frequency of this mutant allele has changed rapidly both in time (during the last two millennia) and in space (across Eurasia

Is Spatial Distribution of the HIV-1-resistant CCR5Delta32 Allele Formed by Ecological Factors?

It has been proposed that the D 32 mutation in the chemokine receptor gene, inducing resistance to HIV-1 and, probably, to other virus infections, has undergone selection in historical times. The frequency of this mutant allele has changed rapidly both in time (during the last two millennia) and in space (across Eurasia)yesBS

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

Characterizing the genetic history of admixture across inner Eurasia

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 genome-wide data of two Eneolithic individuals (~5,400 years before present) associated with the Botai culture in northern Kazakhstan. We find that inner Eurasian populations are structured into three distinct admixture clines stretching between various western and eastern Eurasian ancestries. This genetic separation is well mirrored by geography. The ancient Botai genomes suggest yet another layer of admixture in inner Eurasia that involves Mesolithic hunter-gatherers in Europe, the Upper Paleolithic southern Siberians and East Asians. Admixture modeling of ancient and modern populations suggests an overwriting of this ancient structure in the Altai-Sayan region by migrations of western steppe herders, but partial retaining of this ancient North Eurasian-related cline further to the North. 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

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

© 2015 Karmin et al. 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

Combat : hebdomadaire du Mouvement de libération française

16 février 19431943/02/16 (N92)-1943/02/16

Genomic analyses inform on migration events during the peopling of Eurasia

High-coverage whole-genome sequence studies have so far focused on a limited number1 of geographically restricted populations2,3,4,5, or been targeted at specific diseases, such as cancer6. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history7,8,9 and refuelled the debate on the mutation rate in humans10. 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 record11, and admixture between AMHs and Neanderthals predating the main Eurasian expansion12, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago