scholarly journals Exploring functional variation affecting ceRNA regulation in humans

2015 ◽  
Author(s):  
Mulin Jun Li ◽  
Jiexing Wu ◽  
Peng Jiang ◽  
Wei Li ◽  
Yun Zhu ◽  
...  
Keyword(s):  
Genetic Effect ◽  
Systematic Investigation ◽  
Human Populations ◽  
Functional Variation ◽  
Regulatory Variants ◽  
Genome Wide ◽  
Competing Endogenous Rnas ◽  
Mirna Sponges ◽  
Cis And Trans

MicroRNA (miRNA) sponges have been shown to function as competing endogenous RNAs (ceRNAs) to regulate the expression of other miRNA targets in the network by sequestering available miRNAs. As the first systematic investigation of the genome-wide genetic effect on ceRNA regulation, we applied multivariate response regression and identified widespread genetic variations that are associated with ceRNA competition using 462 Geuvadis RNA-seq data in multiple human populations. We showed that SNPs in gene 3’UTRs at the miRNA seed binding regions can simultaneously regulate gene expression changes in both cis and trans by the ceRNA mechanism. We termed these loci as endogenous miRNA sponge expression quantitative trait loci or “emsQTLs”, and found that a large number of them were unexplored in conventional eQTL mapping. We identified many emsQTLs are undergoing recent positive selection in different human populations. Using GWAS results, we found that emsQTLs are significantly enriched in traits/diseases associated loci. Functional prediction and prioritization extend our understanding on causality of emsQTL allele in disease pathways. We illustrated that emsQTL can synchronously regulate the expression of tumor suppressor and oncogene through ceRNA competition in angiogenesis. Together these results provide a distinct catalog and characterization of functional noncoding regulatory variants that control ceRNA crosstalk.

scholarly journals Genome-wide detection and characterization of positive selection in human populations

Nature ◽  
2007 ◽  
Vol 449 (7164) ◽  
pp. 913-918 ◽  
Author(s):  
Pardis C. Sabeti ◽  
◽  
Patrick Varilly ◽  
Ben Fry ◽  
Jason Lohmueller ◽  
...  
Keyword(s):  
Positive Selection ◽  
Human Populations ◽  
Genome Wide

scholarly journals Chromosome-Wide Characterization of Intragenic Crossover in Shiitake Mushroom, Lentinula edodes

2021 ◽  
Vol 7 (12) ◽  
pp. 1076
Author(s):  
Wenbing Gong ◽  
Nan Shen ◽  
Lin Zhang ◽  
Yinbing Bian ◽  
Yang Xiao
Keyword(s):  
Lentinula Edodes ◽  
Critical Role ◽  
Central Component ◽  
Nucleotide Polymorphisms ◽  
Single Spore ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Cis And Trans ◽  
Qtls Mapping

Meiotic crossover plays a critical role in generating genetic variations and is a central component of breeding. However, our understanding of crossover in mushroom-forming fungi is limited. Here, in Lentinula edodes, we characterized the chromosome-wide intragenic crossovers, by utilizing the single-nucleotide polymorphisms (SNPs) datasets of an F1 haploid progeny. A total of 884 intragenic crossovers were identified in 110 single-spore isolates, the majority of which were closer to transcript start sites. About 71.5% of the intragenic crossovers were clustered into 65 crossover hotspots. A 10 bp motif (GCTCTCGAAA) was significantly enriched in the hotspot regions. Crossover frequencies around mating-type A (MAT-A) loci were enhanced and formed a hotspot in L. edodes. Genome-wide quantitative trait loci (QTLs) mapping identified sixteen crossover-QTLs, contributing 8.5–29.1% of variations. Most of the detected crossover-QTLs were co-located with crossover hotspots. Both cis- and trans-QTLs contributed to the nonuniformity of crossover along chromosomes. On chr2, we identified a QTL hotspot that regulated local, global crossover variation and crossover hotspot in L. edodes. These findings and observations provide a comprehensive view of the crossover landscape in L. edodes, and advance our understandings of conservation and diversity of meiotic recombination in mushroom-forming fungi.

scholarly journals Genome-wide Characterization of Shared and Distinct Genetic Components that Influence Blood Lipid Levels in Ethnically Diverse Human Populations

2013 ◽  
Vol 92 (6) ◽  
pp. 904-916 ◽  
Author(s):  
Marc A. Coram ◽  
Qing Duan ◽  
Thomas J. Hoffmann ◽  
Timothy Thornton ◽  
Joshua W. Knowles ◽  
...  
Keyword(s):  
Ethnically Diverse ◽  
Blood Lipid ◽  
Human Populations ◽  
Lipid Levels ◽  
Genetic Components ◽  
Genome Wide ◽  
Blood Lipid Levels

scholarly journals Presence and Transmission of Mitochondrial Heteroplasmic Mutations in Human Populations of European and African Ancestry

2020 ◽  
Author(s):  
Chunyu Liu ◽  
Jessica L. Fetterman ◽  
Yong Qian ◽  
Xianbang Sun ◽  
Kaiyu Yan ◽  
...  
Keyword(s):  
Tyrosine Phosphatase ◽  
African Ancestry ◽  
Functional Characterization ◽  
Nuclear Genome ◽  
Human Populations ◽  
Sibling Pairs ◽  
Coding Regions ◽  
Genome Wide ◽  
A Genome

ABSTRACTWe investigated the concordance of mitochondrial DNA heteroplasmic mutations (heteroplasmies) in different types of maternal pairs (n=6,745 pairs) of European (EA, n=4,718 pairs) and African (AA, n=2,027 pairs) Americans with whole genome sequences (WGSs). The average concordance rate of heteroplasmies was highest between mother-offspring pairs, followed by sibling-sibling pairs and more distantly related maternal pairs in both EA and AA participants. The allele fractions of concordant heteroplasmies exhibited high correlation (R2=0.8) between paired individuals. Compared to concordant heteroplasmies, discordant ones were more likely to locate in coding regions, be nonsynonymous or nonsynonymous-deleterious (p<0.001). The average number of heteroplasmies per individual (i.e. heteroplasmic burden) was at a similar level until older age (70-80 years old) and increased significantly thereafter (p<0.01). The burden of deleterious heteroplasmies (combined annotation-dependent depletion score≥15), however, was significantly correlated with advancing age (20-44, 45-64, ≥65 years, p-trend=0.01). A genome-wide association analysis of the heteroplasmic burden identified many significant (P<5e-8) common variants (minor allele frequency>0.05) at 11p11.12. Many of the top SNPs act as strong long-range cis regulators of protein tyrosine phosphatase receptor type J. This study provides further evidence that mtDNA heteroplasmies may be inherited or somatic. Somatic heteroplasmic variants increase with advancing age and are more likely to have an adverse impact on mitochondrial function. Further studies are warranted for functional characterization of the deleterious heteroplasmies occurring with advancing age and the association of the 11p11.12 region of the nuclear genome with mtDNA heteroplasmy.

scholarly journals Mining SNPs From EST Databases

1999 ◽  
Vol 9 (2) ◽  
pp. 167-174 ◽  
Author(s):  
Leslie Picoult-Newberg ◽  
Trey E. Ideker ◽  
Mark G. Pohl ◽  
Scott L. Taylor ◽  
Miriam A. Donaldson ◽  
...  
Keyword(s):  
Expressed Sequence Tag ◽  
De Novo ◽  
Cdna Libraries ◽  
Human Populations ◽  
Data Sets ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Using Data

There is considerable interest in the discovery and characterization of single nucleotide polymorphisms (SNPs) to enable the analysis of the potential relationships between human genotype and phenotype. Here we present a strategy that permits the rapid discovery of SNPs from publicly available expressed sequence tag (EST) databases. From a set of ESTs derived from 19 different cDNA libraries, we assembled 300,000 distinct sequences and identified 850 mismatches from contiguous EST data sets (candidate SNP sites), without de novo sequencing. Through a polymerase-mediated, single-base, primer extension technique, Genetic Bit Analysis (GBA), we confirmed the presence of a subset of these candidate SNP sites and have estimated the allele frequencies in three human populations with different ethnic origins. Altogether, our approach provides a basis for rapid and efficient regional and genome-wide SNP discovery using data assembled from sequences from different libraries of cDNAs.[The SNPs identified in this study can be found in the National Center of Biotechnology (NCBI) SNP database under submitter handles ORCHID (SNPS-981210-A) and debnick (SNPS-981209-A and SNPS-981209-B).]

scholarly journals Characterization of Host lncRNAs in Response to Vibrio splendidus Infection and Function as Efficient miRNA Sponges in Sea Cucumber

2021 ◽  
Vol 12 ◽  
Author(s):  
Siyuan Zhang ◽  
Yina Shao ◽  
Chenghua Li
Keyword(s):  
Sea Cucumber ◽  
Apostichopus Japonicus ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Vibrio Splendidus ◽  
Host Interactions ◽  
Competing Endogenous Rnas ◽  
Mirna Sponges ◽  
And Function

Long non-coding RNAs (lncRNAs) have been reported to play critical roles during pathogen infection and innate immune response in mammals. Such observation inspired us to explore the expression profiles and functions of lncRNAs in invertebrates upon bacterial infection. Here, the lncRNAs of sea cucumber (Apostichopus japonicus) involved in Vibrio splendidus infection were characterized. RNA-seq obtained 2897 differentially expressed lncRNAs from Vibrio splendidus infected coelomocytes of sea cucumbers. The potential functions of the significant differentially expressed lncRNAs were related to immunity and metabolic process based on the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Moreover, we identify a lncRNA (XLOC_028509), which is downregulated with Vibrio splendidus challenged, further study indicated that XLOC_028509 adsorb miR-2008 and miR-31 as competing endogenous RNAs (ceRNAs) through base complementarity, which in turn decreased the amount of miRNAs (microRNAs) bound to the 3’UTRs (untranslated regions) of mRNAs to reduce their inhibition of target gene translation. These data demonstrated that the lncRNAs of invertebrates might be important regulators in pathogen-host interactions by sponging miRNAs.

scholarly journals The genetic basis of cis-regulatory divergence between the subspecies of cultivated rice (Oryza sativa)

2019 ◽  
Author(s):  
Malachy T Campbell ◽  
Qian Du ◽  
Kan Liu ◽  
Sandeep Sharma ◽  
Chi Zhang ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Phenotypic Variability ◽  
Cultivated Rice ◽  
Regulatory Variation ◽  
Selective Pressures ◽  
Regulatory Variants ◽  
Genome Wide ◽  
Comprehensive Characterization ◽  
Transcriptome Level

AbstractCultivated rice consists of two subspecies, Indica and Japonica, that exhibit well-characterized differences at the morphological and genetic levels. However, the differences between these subspecies at the transcriptome level remains largely unexamined. Here, we provide a comprehensive characterization of transcriptome divergence and cis-regulatory variation within rice using transcriptome data from 91 accessions from a rice diversity panel (RDP1). The transcriptomes of the two subspecies of rice are highly divergent. The expression and genetic diversity was significantly lower within Japonica relative to Indica, which is consistent with the known population bottleneck during Japonica domestication. Moreover, 1,860 and 1,325 genes showed differences in heritability in the broad and narrow sense respectively, between the subspecies, which was driven largely by environmental and genetic effects rather than differences in phenotypic variability. We leveraged high-density genotypic data and transcript levels to identify cis-regulatory variants that may explain the genetic divergence between the subspecies. We identified significantly more eQTL that were specific to the Indica subspecies compared to Japonica, suggesting that the observed differences in expression and genetic variability also extends to cis-regulatory variation. We next explored the potential causes of this cis-regulatory divergence by assessing local genetic diversity for cis-eQTL. Local genetic diversity around subspecies-specific cis-eQTL was significantly lower than genome-wide averages in subspecies lacking the eQTL, suggesting that selective pressures may have shaped regulatory variation in each subspecies. This study provides the first comprehensive characterization of transcriptional and cis-regulatory variation in cultivated rice, and could be an important resource for future studies.

scholarly journals Intra- and inter-chromosomal chromatin interactions mediate genetic effects on regulatory networks

2017 ◽  
Author(s):  
O. Delaneau ◽  
M. Zazhytska ◽  
C. Borel ◽  
C. Howald ◽  
S. Kumar ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Cell Types ◽  
Regulatory Elements ◽  
Regulatory Domains ◽  
Regulatory Variants ◽  
Chromatin Interactions ◽  
Expression Of Genes ◽  
Genome Wide ◽  
Cell Type Specific ◽  
Cis And Trans

SummaryGenome-wide studies on the genetic basis of gene expression and the structural properties of chromatin have considerably advanced our understanding of the function of the human genome. However, it remains unclear how structure relates to function and, in this work, we aim at bridging both by assembling a dataset that combines the activity of regulatory elements (e.g. enhancers and promoters), expression of genes and genetic variations of 317 individuals and across two cell types. We show that the regulatory activity is structured within 12,583 Cis Regulatory Domains (CRDs) that are cell type specific and highly reflective of the local (i.e. Topologically Associating Domains) and global (i.e. A/B nuclear compartments) nuclear organization of the chromatin. These CRDs essentially delimit the sets of active regulatory elements involved in the transcription of most genes, thereby capturing complex regulatory networks in which the effects of regulatory variants are propagated and combined to finally mediate expression Quantitative Trait Loci. Overall, our analysis reveals the complexity and specificity of cis and trans regulatory networks and their perturbation by genetic variation.

scholarly journals Resolving the insertion sites of polymorphic duplications reveals a HERC2 haplotype under selection

2018 ◽  
Author(s):  
M. Saitou ◽  
O. Gokcumen
Keyword(s):  
Phenotypic Diversity ◽  
Human Populations ◽  
Related Gene ◽  
Partial Duplication ◽  
Future Studies ◽  
Evolutionary Forces ◽  
Genome Wide ◽  
Insertion Sites ◽  
Reference Genomes

ABSTRACTPolymorphic duplications in humans have been shown to contribute to phenotypic diversity. However, the evolutionary forces that maintain variable duplications across the human genome are largely unexplored. To understand the haplotypic architecture of the derived duplications, we developed a linkage-disequilibrium based method to detect insertion sites of polymorphic duplications not represented in reference genomes. This method also allows resolution of haplotypes harboring the duplications. Using this approach, we conducted genome-wide analyses and identified the insertion sites of 22 common polymorphic duplications. We found that the majority of these duplications are intrachromosomal and only one of them is an interchromosomal insertion. Further characterization of these duplications revealed significant associations to blood and skin phenotypes. Based on population genetics analyses, we found that the partial duplication of a well-characterized pigmentation-related gene, HERC2, may be selected against in European populations. We further demonstrated that the haplotype harboring the partial duplication significantly affects the expression of the HERC2P9 gene in multiple tissues. Our study sheds light onto the evolutionary impact of understudied polymorphic duplications in human populations and presents methodological insights for future studies.

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