We sequenced 122 miRNAs in 10 primate species to reveal conservation characteristics of miRNA genes. Strong conservation is observed in stems of miRNA hairpins and increased variation in loop sequences. Interestingly, a striking drop in... more
We sequenced 122 miRNAs in 10 primate species to reveal conservation characteristics of miRNA genes. Strong conservation is observed in stems of miRNA hairpins and increased variation in loop sequences. Interestingly, a striking drop in conservation was found for sequences immediately flanking the miRNA hairpins. This characteristic profile was employed to predict novel miRNAs using cross-species comparisons. Nine hundred and seventy-six candidate miRNAs were identified by scanning whole-genome human/mouse and human/rat alignments. Most of the novel candidates are conserved also in other vertebrates (dog, cow, chicken, opossum, zebrafish). Northern blot analysis confirmed the expression of mature miRNAs for 16 out of 69 representative candidates. Additional support for the expression of 179 novel candidates can be found in public databases, their presence in gene clusters, and literature that appeared after these predictions were made. Taken together, these results suggest the presence of significantly higher numbers of miRNAs in the human genome than previously estimated.
Research Interests:
Genetic variation in genomes is organized in haplotype blocks, and species-specific block structure is defined by differential contribution of population history effects in combination with mutation and recombination events. Haplotype... more
Genetic variation in genomes is organized in haplotype blocks, and species-specific block structure is defined by differential contribution of population history effects in combination with mutation and recombination events. Haplotype maps characterize the common patterns of linkage disequilibrium in populations and have important applications in the design and interpretation of genetic experiments. Although evolutionary processes are known to drive the selection of individual polymorphisms, their effect on haplotype block structure dynamics has not been shown. Here, we present a high-resolution haplotype map for a 5-megabase genomic region in the rat and compare it with the orthologous human and mouse segments. Although the size and fine structure of haplotype blocks are species dependent, there is a significant interspecies overlap in structure and a tendency for blocks to encompass complete genes. Extending these findings to the complete human genome using haplotype map phase I d...
Research Interests: Genetics, Polymorphism, Structural Dynamics, Molecular Evolution, Mammals, and 14 moreHumans, Mice, Haplotypes, Population History, Animals, High Resolution, Human Genome, Fine Structure Constant, Rats, Linkage Disequilibrium, PLoS Genetics, Genetic Recombination, Genetic variation, and Species Specificity
The rat is one of the most important model organisms for biomedical and pharmacological research. However, the generation of novel models for studying specific aspects of human diseases largely depends on selection for specific traits... more
The rat is one of the most important model organisms for biomedical and pharmacological research. However, the generation of novel models for studying specific aspects of human diseases largely depends on selection for specific traits using existing rat strains, thereby solely depending on naturally occurring variation. This study aims to provide the tools to manipulate the rat genome in a more directed way. We developed robust, automated, and scaleable reverse genetic methodology based on ENU (N-ethyl-N-nitrosourea)-driven target-selected mutagenesis. Optimal mutagenesis conditions have been determined in three different rat strains and a universal, rapid, and cost-effective dideoxy resequencing-based screening setup was established for mutation discovery. The effectiveness of the approach is illustrated by the identification of 120 induced mutations in a set of genes of interest, including six that result in unique rat knockout models due to the introduction of premature stop codo...
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Research Interests:
Single nucleotide polymorphisms (SNPs) are the most common source of genetic variation in populations and are thus most likely to account for the majority of phenotypic and behavioral differences between individuals or strains. Although... more
Single nucleotide polymorphisms (SNPs) are the most common source of genetic variation in populations and are thus most likely to account for the majority of phenotypic and behavioral differences between individuals or strains. Although the rat is extensively studied for the latter, data on naturally occurring polymorphisms are mostly lacking. We have used publicly available sequences consisting of whole-genome shotgun
Research Interests: Genetics, Polymorphism, Soccer, Biological Sciences, Software, and 42 morePhylogeny, Cell line, Environmental Sciences, Brain, Humans, Expressed Sequence Tags, Animals, Male, Statistical Significance, Young Adult, Genetic Map, Fisheries Sciences, Genome, Proteins, Risk factors, Inflammatory disease, Protein Function, Clinical Sciences, Cost Efficiency, Elastin, Genotype, Rats, Adult, Success Rate, Single Nucleotide Polymorphism, Time Factors, Soft Tissue Injuries, Genetic variation, Risk Factors, Ease of Use, Genome sequence, Gel electrophoresis, Chronic Periodontitis, Dermatitis, In Silico, Intracranial Arteriovenous Malformations, Transcription Start Site, Predictive value of tests, Software Validation, Nucleotides, Biochemistry and cell biology, and Web Interface
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Research Interests: Genetics, Polymorphism, Biological Sciences, DNA, Association study, and 15 morePhylogeny, Automation, Mice, Haplotypes, Animals, Polymerase Chain Reaction, Genome, Human health, Genotype, Rats, Single Nucleotide Polymorphism, Genetic variation, Genome sequence, Species Specificity, and Point of View
Research Interests: Comparative sequence analysis, Genomics, Polymorphism, Computational Biology, Danio rerio, and 19 moreBiological Sciences, Software, Sequence alignment, Expressed Sequence Tags, Animals, Primer design, Information Storage and Retrieval, Rats, Single Nucleotide Polymorphism, Very high throughput, Genetic variation, Zebrafish, Genome sequence, Universal Access, Large Scale, In Silico, Experimental Data, Hidden Information, and Internet
Research Interests: Genetics, Polymorphism, Structural Dynamics, Molecular Evolution, Mammals, and 14 moreHumans, Mice, Haplotypes, Population History, Animals, High Resolution, Human Genome, Fine Structure Constant, Rats, Linkage Disequilibrium, PLoS Genetics, Genetic Recombination, Genetic variation, and Species Specificity
Advancing our understanding of embryonic development is heavily dependent on identification of novel pathways or regulators. Although genome-wide techniques such as RNA sequencing are ideally suited for discovering novel candidate genes,... more
Advancing our understanding of embryonic development is heavily dependent on identification of novel pathways or regulators. Although genome-wide techniques such as RNA sequencing are ideally suited for discovering novel candidate genes, they are unable to yield spatially resolved information in embryos or tissues. Microscopy-based approaches, using in situ hybridization, for example, can provide spatial information about gene expression, but are limited to analyzing one or a few genes at a time. Here, we present a method where we combine traditional histological techniques with low-input RNA sequencing and mathematical image reconstruction to generate a high-resolution genome-wide 3D atlas of gene expression in the zebrafish embryo at three developmental stages. Importantly, our technique enables searching for genes that are expressed in specific spatial patterns without manual image annotation. We envision broad applicability of RNA tomography as an accurate and sensitive approach for spatially resolved transcriptomics in whole embryos and dissected organs.
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Research Interests: Computational Biology, Gene expression, DISTRIBUTION, Biological Sciences, DNA, and 15 moreHumans, Animals, Nucleic acid hybridization, Genome, Rats, Rat, Quantitative Trait Loci, Distribution, Human Disease, DNA Copy Number, Complex Traits, Genetic Variability, Chromosomes, Experimental Method, and Gene Expression Data
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Research Interests: Evolutionary Biology, Genetics, Zoology, Polymorphism, Molecular Evolution, and 17 moreSequence Analysis, Globin, DNA, Phylogeny, Mitochondrial DNA, Animals, DNA sequence design, Cytochrome c oxidase, Chironomidae, Molecular phylogeny, Molecular Phylogenetics and Evolution, Molecular phylogenetics, Cytochrome B, Phylogenetic Tree, Maximum Parsimony, Cytochrome Oxidase I, and DNA sequence
Research Interests: Cellular Biology, Molecular Biology, Genomics, Cancer, Gene expression, and 16 moreColorectal cancer, Biological Sciences, DNA, Cell line, Molecular and cellular biology, Humans, Wnt Signaling, DNA Array, Chromatin, Human Genome, DNA binding, Base Sequence, Protein Binding, Binding Site, Transcription Start Site, and Colorectal Neoplasms
Body weight is one of the most important economic traits in the poultry industry. In the present study, a custom SNP Beadchip was used to analyze the association between those 15 SNPs and 12 growth traits of Jinghai yellow chickens, and... more
Body weight is one of the most important economic traits in the poultry industry. In the present study, a custom SNP Beadchip was used to analyze the association between those 15 SNPs and 12 growth traits of Jinghai yellow chickens, and other important genetic parameters were also calculated and analyzed. The results indicated that nine of the 15 SNPs were associated with growth traits in Jinghai yellow chickens (P < 0.05), and the identified SNPs were also in linkage disequilibrium. Five of the nine identified SNPs were mainly associated with all of the growth traits, which indicated that those five SNPs might have significant influence on Jinghai yellow chicken growth traits. Polymorphism information content (PIC) analyses indicated that five of the nine SNPs exhibited moderate polymorphism (0.25 < PIC < 0.5), which reflected intermediate genetic diversity. Six candidate genes surrounding the significant SNPs were obtained and subjected to Gene Ontology annotation analyses and pathway analyses. The functions of six important candidate genes (SETDB2, ATP7B, INTS6, KPNA3, DLEU7, and FOXO1A) were discussed. The present study provided basic data for marker-assisted selection in Jinghai yellow chickens.
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Research Interests:
Research Interests:
Research Interests:
Research Interests:
We sequenced 122 miRNAs in 10 primate species to reveal conservation characteristics of miRNA genes. Strong conservation is observed in stems of miRNA hairpins and increased variation in loop sequences. Interestingly, a striking drop in... more
We sequenced 122 miRNAs in 10 primate species to reveal conservation characteristics of miRNA genes. Strong conservation is observed in stems of miRNA hairpins and increased variation in loop sequences. Interestingly, a striking drop in conservation was found for sequences immediately flanking the miRNA hairpins. This characteristic profile was employed to predict novel miRNAs using cross-species comparisons. Nine hundred and seventy-six candidate miRNAs were identified by scanning whole-genome human/mouse and human/rat alignments. Most of the novel candidates are conserved also in other vertebrates (dog, cow, chicken, opossum, zebrafish). Northern blot analysis confirmed the expression of mature miRNAs for 16 out of 69 representative candidates. Additional support for the expression of 179 novel candidates can be found in public databases, their presence in gene clusters, and literature that appeared after these predictions were made. Taken together, these results suggest the presence of significantly higher numbers of miRNAs in the human genome than previously estimated.