Abstract:
:To understand disease mechanisms, a large-scale analysis of human-yeast genetic interactions was performed. Of 1305 human disease genes assayed, 20 genes exhibited strong toxicity in yeast. Human-yeast genetic interactions were identified by en masse transformation of the human disease genes into a pool of 4653 homozygous diploid yeast deletion mutants with unique barcode sequences, followed by multiplexed barcode sequencing to identify yeast toxicity modifiers. Subsequent network analyses focusing on amyotrophic lateral sclerosis (ALS)-associated genes, such as optineurin (OPTN) and angiogenin (ANG), showed that the human orthologs of the yeast toxicity modifiers of these ALS genes are enriched for several biological processes, such as cell death, lipid metabolism, and molecular transport. When yeast genetic interaction partners held in common between human OPTN and ANG were validated in mammalian cells and zebrafish, MAP2K5 kinase emerged as a potential drug target for ALS therapy. The toxicity modifiers identified in this study may deepen our understanding of the pathogenic mechanisms of ALS and other devastating diseases.
journal_name
Genome Resjournal_title
Genome researchauthors
Jo M,Chung AY,Yachie N,Seo M,Jeon H,Nam Y,Seo Y,Kim E,Zhong Q,Vidal M,Park HC,Roth FP,Suk Kdoi
10.1101/gr.211649.116subject
Has Abstractpub_date
2017-09-01 00:00:00pages
1487-1500issue
9eissn
1088-9051issn
1549-5469pii
gr.211649.116journal_volume
27pub_type
杂志文章相关文献
GENOME RESEARCH文献大全abstract::To accelerate the molecular analysis of behavior in the honey bee (Apis mellifera), we created expressed sequence tag (EST) and cDNA microarray resources for the bee brain. Over 20,000 cDNA clones were partially sequenced from a normalized (and subsequently subtracted) library generated from adult A. mellifera brains....
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.5302
更新日期:2002-04-01 00:00:00
abstract::The repressive capacity of cytosine DNA methylation is mediated by recruitment of silencing complexes by methyl-CpG binding domain (MBD) proteins. Despite MBD proteins being associated with silencing, we discovered that a family of arthropod Copia retrotransposons have incorporated a host-derived MBD. We functionally ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.243774.118
更新日期:2019-08-01 00:00:00
abstract::Gene amplification occurs in most solid tumors and is associated with poor prognosis. Amplification of 20q13.2 is common to several tumor types including breast cancer. The 1 Mb of sequence spanning the 20q13.2 breast cancer amplicon is one of the most exhaustively studied segments of the human genome. These studies h...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.gr1743r
更新日期:2001-06-01 00:00:00
abstract::Cys2-His2 zinc finger proteins (ZFPs) are the largest group of transcription factors in higher metazoans. A complete characterization of these ZFPs and their associated target sequences is pivotal to fully annotate transcriptional regulatory networks in metazoan genomes. As a first step in this process, we have charac...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.151472.112
更新日期:2013-06-01 00:00:00
abstract::The determination of the phylogenetic relationships among microorganisms has long relied primarily on gene sequence information. Given that prokaryotic organisms often lack morphological characteristics amenable to phylogenetic analysis, prokaryotic phylogenies, in particular, are often based on sequence data. In this...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.3033805
更新日期:2005-03-01 00:00:00
abstract::Metagenomic projects generate short, overlapping fragments of DNA sequence, each deriving from a different individual. We report a new method for inferring the scaled mutation rate, theta = 2Neu, and the scaled exponential growth rate, R = Ner, from the site-frequency spectrum of these data while accounting for sequen...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.5431206
更新日期:2006-10-01 00:00:00
abstract::The need to translate genes to function has positioned the rat as an invaluable animal model for genomic research. The significant increase in genomic resources in recent years has had an immediate functional application in the rat. Many of the resources for translational research are already in place and are ready to...
journal_title:Genome research
pub_type: 杂志文章,评审
doi:10.1101/gr.3744005
更新日期:2005-12-01 00:00:00
abstract::Transposable elements (TEs) are an integral part of the host transcriptome. TE-containing noncoding RNAs (ncRNAs) show considerable tissue specificity and play important roles during development, including stem cell maintenance and cell differentiation. Recent advances in single-cell RNA-seq (scRNA-seq) revolutionized...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.265173.120
更新日期:2021-01-01 00:00:00
abstract::The alignment of full-length human cDNA sequences to the finished sequence of the human genome provides a unique opportunity to study the distribution of genes throughout the genome. By analyzing the distances between 23,752 genes, we identified a class of divergently transcribed gene pairs, representing more than 10%...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.1982804
更新日期:2004-01-01 00:00:00
abstract::Structured elements of RNA molecules are essential in, e.g., RNA stabilization, localization, and protein interaction, and their conservation across species suggests a common functional role. We computationally screened vertebrate genomes for conserved RNA structures (CRSs), leveraging structure-based, rather than seq...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.208652.116
更新日期:2017-08-01 00:00:00
abstract::Regulatory sequences in higher genomes can map large distances from gene coding regions, and cannot yet be identified by simple inspection of primary DNA sequence information. Here we describe an efficient method of surveying large genomic regions for gene regulatory information, and subdividing complex sets of distan...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.1306003
更新日期:2003-09-01 00:00:00
abstract::Recent computational and experimental work suggests that functional modules underlie much of cellular physiology and are a useful unit of cellular organization from the perspective of systems biology. Because interactions among modules can give rise to higher-level properties that are essential to cellular function, a...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.3847105
更新日期:2005-09-01 00:00:00
abstract::Mammalian X and Y Chromosomes evolved from an ordinary autosomal pair. Genetic decay of the Y led to X Chromosome inactivation (XCI) in females, but some Y-linked genes were retained during the course of sex chromosome evolution, and many X-linked genes did not become subject to XCI. We reconstructed gene-by-gene dosa...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.230433.117
更新日期:2018-04-01 00:00:00
abstract::More than 25 loci have been linked to type 1 diabetes (T1D) in the nonobese diabetic (NOD) mouse, but identification of the underlying genes remains challenging. We describe here the positional cloning of a T1D susceptibility locus, Idd11, located on mouse chromosome 4. Sequence analysis of a series of congenic NOD mo...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.101881.109
更新日期:2010-12-01 00:00:00
abstract::Notwithstanding their biological importance, Y chromosomes remain poorly known in most species. A major obstacle to their study is the identification of Y chromosome sequences; due to its high content of repetitive DNA, in most genome projects, the Y chromosome sequence is fragmented into a large number of small, unma...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.156034.113
更新日期:2013-11-01 00:00:00
abstract::The maternal and paternal copies of the genome are both required for mammalian development, and this is primarily due to imprinted genes, those that are monoallelically expressed based on parent-of-origin. Typically, this pattern of expression is regulated by differentially methylated regions (DMRs) that are establish...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.196139.115
更新日期:2016-06-01 00:00:00
abstract::Evolutionary constraints on gene regulatory elements are poorly understood: Little is known about how the strength of transcription factor binding correlates with DNA sequence conservation, and whether transcription factor binding sites can evolve rapidly while retaining their function. Here we use the model of the NF...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.6490707
更新日期:2007-09-01 00:00:00
abstract::In plants there are several classes of 21-24-nt short RNAs that regulate gene expression. The most conserved class is the microRNAs (miRNAs), although some miRNAs are found only in specific species. We used high-throughput pyrosequencing to identify conserved and nonconserved miRNAs and other short RNAs in tomato frui...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.080127.108
更新日期:2008-10-01 00:00:00
abstract::Essential genes refer to those whose null mutation leads to lethality or sterility. Theoretical reasoning and empirical data both suggest that the fatal effect of inactivating an essential gene can be attributed to either the loss of indispensable core cellular function (Type I), or the gain of fatal side effects afte...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.205955.116
更新日期:2016-10-01 00:00:00
abstract::Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regu...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.209940.116
更新日期:2017-02-01 00:00:00
abstract::Here we use a chromosome-level genome assembly of a prairie rattlesnake (Crotalus viridis), together with Hi-C, RNA-seq, and whole-genome resequencing data, to study key features of genome biology and evolution in reptiles. We identify the rattlesnake Z Chromosome, including the recombining pseudoautosomal region, and...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.240952.118
更新日期:2019-04-01 00:00:00
abstract::Recent studies have analyzed large-scale data sets of gene expression to identify genes associated with interindividual variation in phenotypes ranging from cancer subtypes to drug sensitivity, promising new avenues of research in personalized medicine. However, gene expression data alone is limited in its ability to ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.227066.117
更新日期:2018-08-01 00:00:00
abstract::The recent publication of the FANTOM mouse transcriptome has provided a unique opportunity to study the diversity of transcripts arising from a single gene locus. We have focused on the Gnas complex, as imprinting loci themselves provide unique insights into transcriptional regulation. Thirteen full-length cDNAs from ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.955503
更新日期:2003-06-01 00:00:00
abstract::We have generated an improved assembly and gene annotation of the pig X Chromosome, and a first draft assembly of the pig Y Chromosome, by sequencing BAC and fosmid clones from Duroc animals and incorporating information from optical mapping and fiber-FISH. The X Chromosome carries 1033 annotated genes, 690 of which a...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.188839.114
更新日期:2016-01-01 00:00:00
abstract::In this communication, we describe the use of specialized transposons (Tn5 derivatives) to create deletions in the Escherichia coli K-12 chromosome. These transposons are essentially rearranged composite transposons that have been assembled to promote the use of the internal transposon ends, resulting in intramolecula...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.611403
更新日期:2003-04-01 00:00:00
abstract::The nuclear space is not a homogeneous biochemical environment. Many studies have demonstrated that the transcriptional activity of a gene is linked to its positioning within the nuclear space. Following the discovery of lamin-associated domains (LADs), which are transcriptionally repressed chromatin regions, the nonr...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.215186.116
更新日期:2017-07-01 00:00:00
abstract::Spatial organization of different epigenomic marks was used to infer functions of the epigenome. It remains unclear what can be learned from the temporal changes of the epigenome. Here, we developed a probabilistic model to cluster genomic sequences based on the similarity of temporal changes of multiple epigenomic ma...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.144949.112
更新日期:2013-02-01 00:00:00
abstract::Eukaryotic translation initiation involves preinitiation ribosomal complex 5'-to-3' directional probing of mRNA for codons suitable for starting protein synthesis. The recognition of codons as starts depends on the codon identity and on its immediate nucleotide context known as Kozak context. When the context is weak ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.257352.119
更新日期:2020-07-01 00:00:00
abstract::Initially thought to play a restricted role in calcium homeostasis, the pleiotropic actions of vitamin D in biology and their clinical significance are only now becoming apparent. However, the mode of action of vitamin D, through its cognate nuclear vitamin D receptor (VDR), and its contribution to diverse disorders, ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.107920.110
更新日期:2010-10-01 00:00:00
abstract::Plasticity of gene regulatory encryption can permit DNA sequence divergence without loss of function. Functional information is preserved through conservation of the composition of transcription factor binding sites (TFBS) in a regulatory element. We have developed a method that can accurately identify pairs of functi...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.119016.110
更新日期:2011-07-01 00:00:00