scholarly journals Analysis of archaic human haplotypes suggest 5-hmC to act as epigenetic guide for meiotic point recombination

2017 ◽  
Author(s):  
Bernett Lee ◽  
Samantha Cyrill ◽  
Wendy Lee ◽  
Rosella Melchiotti ◽  
Anand Andiappan ◽  
...  
Keyword(s):  
Cpg Islands ◽  
Linkage Study ◽  
Recombination Rates ◽  
Functional Regions ◽  
Individual Snps ◽  
Local Point ◽  
Common Process ◽  
Intergenic Regions ◽  
Tight Association ◽  
Homologue Recombination

AbstractMeiotic “point recombination” refers to homologue recombination events affecting only individual SNPs. Driven mostly by gene conversion, it is common process that allows for a gradual adaptation and maturation of haplotypes during genetic evolution. In contrast to crossover recombination it is not tied to predetermined recombination sites and therefore assumed to occur largely randomly. Our analysis of archaic human haplotypes however revealed striking differences in the local point recombination rate. A linkage-study of 1.9 million SNPs defined by the sequence of denisovan hominids revealed low rates in introns and quiescent intergenic regions but high rates in splice sites, exons, 5’- and 3’-UTRs, and CpG islands. Correlations with ChIP-Seq tracks from ENCODE and other public sources identified a number of epigenetic modifications, that associated directly with these recombination events. A particularly tight association was observed for 5-hydroxymethylcytosine marks (5hmC). The mark was enriched in virtually all of the functional regions associated with elevated point recombination rates, including CpG islands and ‘poised’ bivalent regions. As intermediate of oxidative demethylation, 5hmC is also a marker of recently opened gene loci. The data, thus, supports a model of ‘guided’ evolution, in which point recombination is directed by 5hmC marks towards the functionally relevant regions.

Snake Recombination Landscapes Are Concentrated in Functional Regions despite PRDM9

2020 ◽  
Vol 37 (5) ◽  
pp. 1272-1294 ◽  
Author(s):  
Drew R Schield ◽  
Giulia I M Pasquesi ◽  
Blair W Perry ◽  
Richard H Adams ◽  
Zachary L Nikolakis ◽  
...  
Keyword(s):  
Recombination Rate ◽  
Gc Content ◽  
Substantial Variation ◽  
Recombination Rates ◽  
Recombination Hotspots ◽  
Functional Regions ◽  
Intergenic Regions ◽  
Positive Correlations ◽  
Adaptive Role

Abstract Meiotic recombination in vertebrates is concentrated in hotspots throughout the genome. The location and stability of hotspots have been linked to the presence or absence of PRDM9, leading to two primary models for hotspot evolution derived from mammals and birds. Species with PRDM9-directed recombination have rapid turnover of hotspots concentrated in intergenic regions (i.e., mammals), whereas hotspots in species lacking PRDM9 are concentrated in functional regions and have greater stability over time (i.e., birds). Snakes possess PRDM9, yet virtually nothing is known about snake recombination. Here, we examine the recombination landscape and test hypotheses about the roles of PRDM9 in rattlesnakes. We find substantial variation in recombination rate within and among snake chromosomes, and positive correlations between recombination rate and gene density, GC content, and genetic diversity. Like mammals, snakes appear to have a functional and active PRDM9, but rather than being directed away from genes, snake hotspots are concentrated in promoters and functional regions—a pattern previously associated only with species that lack a functional PRDM9. Snakes therefore provide a unique example of recombination landscapes in which PRDM9 is functional, yet recombination hotspots are associated with functional genic regions—a combination of features that defy existing paradigms for recombination landscapes in vertebrates. Our findings also provide evidence that high recombination rates are a shared feature of vertebrate microchromosomes. Our results challenge previous assumptions about the adaptive role of PRDM9 and highlight the diversity of recombination landscape features among vertebrate lineages.

scholarly journals TAGOOS: genome-wide supervised learning of non-coding loci associated to complex phenotypes

2019 ◽  
Vol 47 (14) ◽  
pp. e79-e79
Author(s):  
Aitor González ◽  
Marie Artufel ◽  
Pascal Rihet
Keyword(s):  
Cleft Lip ◽  
Association Studies ◽  
Area Under The Curve ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Functional Snps ◽  
Functional Regions ◽  
Complex Phenotypes ◽  
Genome Wide ◽  
Intergenic Regions

Abstract Genome-wide association studies (GWAS) associate single nucleotide polymorphisms (SNPs) to complex phenotypes. Most human SNPs fall in non-coding regions and are likely regulatory SNPs, but linkage disequilibrium (LD) blocks make it difficult to distinguish functional SNPs. Therefore, putative functional SNPs are usually annotated with molecular markers of gene regulatory regions and prioritized with dedicated prediction tools. We integrated associated SNPs, LD blocks and regulatory features into a supervised model called TAGOOS (TAG SNP bOOSting) and computed scores genome-wide. The TAGOOS scores enriched and prioritized unseen associated SNPs with an odds ratio of 4.3 and 3.5 and an area under the curve (AUC) of 0.65 and 0.6 for intronic and intergenic regions, respectively. The TAGOOS score was correlated with the maximal significance of associated SNPs and expression quantitative trait loci (eQTLs) and with the number of biological samples annotated for key regulatory features. Analysis of loci and regions associated to cleft lip and human adult height phenotypes recovered known functional loci and predicted new functional loci enriched in transcriptions factors related to the phenotypes. In conclusion, we trained a supervised model based on associated SNPs to prioritize putative functional regions. The TAGOOS scores, annotations and UCSC genome tracks are available here: https://tagoos.readthedocs.io.

scholarly journals Identification of Differentially Methylated Regions Associated with a Knockout of SUV39H1 in Prostate Cancer Cells

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1188
Author(s):  
Wenbo Yan ◽  
Yuqi Guo ◽  
Fangxi Xu ◽  
Deepak Saxena ◽  
Xin Li
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
Cell Migration ◽  
Cpg Islands ◽  
Migration And Invasion ◽  
Differentially Methylated Regions ◽  
Functional Regions ◽  
Pathways Analysis ◽  
Cell Shapes ◽  
And Migration

Epigenetic alterations, such as histone methylations, affect the pathogenesis of tumors including prostate cancer (PCa). Previously, we reported that metformin reduced SUV39H1, a histone methyltransferase of H3 Lys9, to inhibit the migration of PCa cells. Since histone methylation is functionally linked to DNA methylation, we speculate that the knockout of the SUV39H1 gene will affect the genomic DNA methylation profile to regulate PCa cell migration and invasion. The genome-wide DNA methylation level is lower in SUV39H1 knockout (KO) cells than wild-type (WT) ones. However, the methylation levels in functional regions of CpG Islands (CGI), 5′ untranslated region (UTR5), and exon regions are higher in KO cells than WT cells. Analysis of differentially methylated regions (DMRs) identified 1241 DMR genes that have differential methylation on CG sites when comparing the KO and WT samples. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes Pathways analysis showed that knockout of SUV39H1 affects gene sets and pathways that are heavily involved in cell shapes, cell recognition, adhesion, motility, and migration. Our study suggests that SUV39H1 plays an important role in PCa migration via the epigenetic regulation of methylation on CG sites, and is a novel and legitimate target to inhibit PCa cell migration.

scholarly journals The Role of H3K4 Trimethylation in CpG Islands Hypermethylation in Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 143
Author(s):  
Giuseppe Zardo
Keyword(s):  
Cpg Islands ◽  
Alternative Promoters ◽  
Cpg Dinucleotides ◽  
H3k4 Trimethylation ◽  
Mammalian Embryogenesis ◽  
Intergenic Regions ◽  
Methylation Patterns ◽  
Unmethylated State

CpG methylation in transposons, exons, introns and intergenic regions is important for long-term silencing, silencing of parasitic sequences and alternative promoters, regulating imprinted gene expression and determining X chromosome inactivation. Promoter CpG islands, although rich in CpG dinucleotides, are unmethylated and remain so during all phases of mammalian embryogenesis and development, except in specific cases. The biological mechanisms that contribute to the maintenance of the unmethylated state of CpG islands remain elusive, but the modification of established DNA methylation patterns is a common feature in all types of tumors and is considered as an event that intrinsically, or in association with genetic lesions, feeds carcinogenesis. In this review, we focus on the latest results describing the role that the levels of H3K4 trimethylation may have in determining the aberrant hypermethylation of CpG islands in tumors.

scholarly journals Comparative Sequence Analysis of the X-Inactivation Center Region in Mouse, Human, and Bovine

2000 ◽  
Vol 12 (6) ◽  
pp. 894-908 ◽  
Author(s):  
Corinne Chureau ◽  
Marine Prissette ◽  
Agnès Bourdet ◽  
Valérie Barbe ◽  
Laurence Cattolico ◽  
...  
Keyword(s):  
Transcriptional Activity ◽  
Sequence Data ◽  
Cpg Islands ◽  
Comparative Sequence Analysis ◽  
X Inactivation ◽  
Asymmetric Distribution ◽  
Repeat Elements ◽  
Link Type ◽  
New Genes ◽  
Intergenic Regions

We have sequenced to high levels of accuracy 714-kb and 233-kb regions of the mouse and bovine X-inactivation centers (Xic), respectively, centered on the Xist gene. This has provided the basis for a fully annotated comparative analysis of the mouse Xic with the 2.3-Mb orthologous region in human and has allowed a three-way species comparison of the core central region, including theXist gene. These comparisons have revealed conserved genes, both coding and noncoding, conserved CpG islands and, more surprisingly, conserved pseudogenes. The distribution of repeated elements, especially LINE repeats, in the mouse Xic region when compared to the rest of the genome does not support the hypothesis of a role for these repeat elements in the spreading of X inactivation. Interestingly, an asymmetric distribution of LINE elements on the two DNA strands was observed in the three species, not only within introns but also in intergenic regions. This feature is suggestive of important transcriptional activity within these intergenic regions. In silico prediction followed by experimental analysis has allowed four new genes, Cnbp2, Ftx, Jpx, and Ppnx, to be identified and novel, widespread, complex, and apparently noncoding transcriptional activity to be characterized in a region 5′ of Xist that was recently shown to attract histone modification early after the onset of X inactivation.[The sequence data described in this paper have been submitted to the EMBL data library under accession nos. AJ421478, AJ421479, AJ421480, andAJ421481. Online supplemental data are available athttp://pbil.univ-lyon1.fr/datasets/Xic2002/data.html andwww.genome.org.]

scholarly journals Stable recombination hotspots in birds

2015 ◽  
Author(s):  
Sonal Singhal ◽  
Ellen Leffler ◽  
Keerthi Sannareddy ◽  
Isaac Turner ◽  
Oliver Venn ◽  
...  
Keyword(s):  
Critical Role ◽  
Cpg Islands ◽  
Natural Populations ◽  
Bird Species ◽  
Indirect Evidence ◽  
Fine Scale ◽  
Recombination Rates ◽  
Transcription Start Sites ◽  
Recombination Hotspots ◽  
Meiotic Recombination Hotspots

Although the DNA-binding protein PRDM9 plays a critical role in the specification of meiotic recombination hotspots in mice and apes, it appears to be absent from many vertebrate species, including birds. To learn about the determinants of fine-scale recombination rates and their evolution in natural populations lacking PRDM9, we inferred fine-scale recombination maps from population resequencing data for two bird species, the zebra finchTaeniopygia guttata, and the long-tailed finch,Poephila acuticauda, whose divergence is on par with that between human and chimpanzee. We find that both bird species have hotspots, and these are enriched near CpG islands and transcription start sites. In sharp contrast to what is seen in mice and apes, the hotspots are largely shared between the two species, with indirect evidence of conservation extending across bird species tens of millions of years diverged. These observations link the evolution of hotspots to their genetic architecture, suggesting that in the absence of PRDM9 binding specificity, accessibility of the genome to the cellular recombination machinery, particularly around functional genomic elements, both enables increased recombination and constrains its evolution.

Antidepressant-Suicide Linkage Study Is Debated

2006 ◽  
Vol 40 (9) ◽  
pp. 33
Author(s):  
MARY ANN MOON
Keyword(s):  
Linkage Study

APLIKASI PENCARI INFORMASI PERMINTAAN LAYANAN WEB YANG ERROR MENGGUNAKAN ALGORITMA BOYER-MOORE

2016 ◽  
Vol 1 (1) ◽  
pp. 001
Author(s):  
Harry Setya Hadi
Keyword(s):  
Data Storage ◽  
Computer Network ◽  
Web Server ◽  
Access Methods ◽  
Ip Address ◽  
String Searching ◽  
Common Process ◽  
Web Server Logs ◽  
Different Parts ◽  
The Web

String searching is a common process in the processes that made the computer because the text is the main form of data storage. Boyer-Moore is the search string from right to left is considered the most efficient methods in practice, and matching string from the specified direction specifically an algorithm that has the best results theoretically. A system that is connected to a computer network that literally pick a web server that is accessed by multiple users in different parts of both good and bad aim. Any activity performed by the user, will be stored in Web server logs. With a log report contained in the web server can help a web server administrator to search the web request error. Web server log is a record of the activities of a web site that contains the data associated with the IP address, time of access, the page is opened, activities, and access methods. The amount of data contained in the resulting log is a log shed useful information.

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