Genome Research (GENOME RES )

Publisher: Cold Spring Harbor Laboratory Press


The journal focuses on genome studies in all species, and presents research that provides or aids in genome-based analyses of biological processes. The journal represents a nexus point where genomic information, applications, and technology come together with biological information to create a more global understanding of all biological systems.

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  • Website
    Genome Research website
  • Other titles
    Genome research (Online), Genome research
  • ISSN
  • OCLC
  • Material type
    Online system or service, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Cold Spring Harbor Laboratory Press

  • Pre-print
    • Archiving status unclear
  • Post-print
    • Archiving status unclear
  • Conditions
    • Publisher will deposit in PubMed Central for public access 6 months after full issue publication (Genome Research, Genes & Development)
    • Learning & Memory and RNA will be deposit on behalf of funded authors for public access 12 months after full issue publication
  • Classification
    ​ white

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Genome-wide association studies (GWAS) identify regions of the genome correlated with disease risk, but are restricted in their ability to identify the underlying causative mechanism(s). Thus, GWAS are useful 'roadmaps' that require functional analysis to establish the genetic and mechanistic structure of a particular locus. Unfortunately, direct functional testing in humans is limited, demonstrating the need for complimentary approaches. Here we used an integrated approach combining zebrafish, rat, and human data to interrogate the function of an established GWAS locus (SHROOM3) lacking prior functional support for chronic kidney disease (CKD). Congenic mapping and sequence analysis in rats suggested Shroom3 was a strong positional candidate gene. Transferring of a 6.1 Mb region containing the wild-type Shroom3 gene significantly improved the kidney glomerular function in FHH (Fawn-Hooded Hypertensive) rat. The wild-type Shroom3 allele, but not the FHH Shroom3 allele, rescued glomerular defects induced by knockdown of endogenous shroom3 in zebrafish, suggesting that the FHH Shroom3 allele is defective and likely contributes to renal injury in the FHH rat. We also show for the first time that variants disrupting the actin-binding domain of SHROOM3 may cause podocyte effacement and impairment of the glomerular filtration barrier.
    Genome Research 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: β-thalassemia, one of the most common genetic diseases worldwide, is caused by mutations in the human hemoglobin beta (HBB) gene. Creation of human induced pluripotent stem cells (iPSCs) from β-thalassemia patients could offer an approach to cure this disease. Correction of the disease-causing mutations in iPSCs could restore normal function and provide a rich source of cells for transplantation. In this study, we used the latest gene-editing tool, CRISPR/Cas9 technology, combined with the piggyBac transposon to efficiently correct the HBB mutations in patient-derived iPSCs without leaving any residual footprint. No off-target effects were detected in the corrected iPSCs, and the cells retain full pluripotency and exhibit normal karyotypes. When differentiated into erythroblasts using a monolayer culture, gene-corrected iPSCs restored expression of HBB compared to the parental iPSCs line. Our study provides an effective approach to correct HBB mutations without leaving any genetic footprint in patient-derived iPSCs, thereby demonstrating a critical step toward the future application of stem cell-based gene therapy to monogenic diseases.
    Genome Research 08/2014; 24:1526-1533.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alternative splicing is the main mechanism of increasing the proteome diversity coded by a limited number of genes. It is well established that different tissues or organs express different splicing variants. However, organs are composed of common major cell types, including fibroblasts, epithelial, and endothelial cells. By analyzing large-scale datasets generated by the ENCODE Project Consortium and after extensive RT-PCR validation, we demonstrate that each of the three major cell types expresses a specific splicing program independently of its organ origin. Furthermore, by analyzing splicing factor expression across samples and publicly available splicing factor binding site datasets (CLIP-seq) and exon array datasets after splicing factor depletion, we identified several splicing factors, including ESRP1 and 2, MBNL1, NOVA1, PTBP1, and RBFOX2 that contribute to establishing these cell type-specific splicing programs. All the analyzed datasets are freely available in an user-friendly web interface named FasterDB, which describes all known splicing variants of human and mouse genes and their splicing pattern across several dozens of normal and cancer cells as well as across tissues. Information regarding splicing factors that potentially contribute to individual exon regulation is also provided via a dedicated CLIP-seq and exon array data visualization interface. To the best of our knowledge, FasterDB is the first database integrating such a variety of large-scale datasets to enable functional genomics analyses at exon-level resolution.
    Genome Research 12/2013;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pigmentation of skin, eye, and hair reflects some of the most evident common phenotypes in humans. Several candidate genes for human pigmentation are identified. The SNP rs12913832 has strong statistical association with human pigmentation. It is located within an intron of the nonpigment gene HERC2, 21 kb upstream of the pigment gene OCA2, and the region surrounding rs12913832 is highly conserved among animal species. However, the exact functional role of HERC2 rs12913832 in human pigmentation is unknown. Here we demonstrate that the HERC2 rs12913832 region functions as an enhancer regulating OCA2 transcription. In darkly pigmented human melanocytes carrying the rs12913832 T-allele, we detected binding of the transcription factors HLTF, LEF1, and MITF to the HERC2 rs12913832 enhancer, and a long-range chromatin loop between this enhancer and the OCA2 promoter that leads to elevated OCA2 expression. In contrast, in lightly pigmented melanocytes carrying the rs12913832 C-allele, chromatin-loop formation, transcription factor recruitment, and OCA2 expression are all reduced. Hence, we demonstrate that allelic variation of a common noncoding SNP located in a distal regulatory element not only disrupts the regulatory potential of this element but also affects its interaction with the relevant promoter. We provide the key mechanistic insight that allele-dependent differences in chromatin-loop formation (i.e., structural differences in the folding of gene loci) result in differences in allelic gene expression that affects common phenotypic traits. This concept is highly relevant for future studies aiming to unveil the functional basis of genetically determined phenotypes, including diseases.
    Genome Research 03/2012; 22:446-455.
  • Genome Research 09/2011;
  • Genome Research 01/2010;
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    ABSTRACT: Transposable elements (TEs) are ubiquitous genomic parasites. The deleterious consequences of the presence and activity of TEs have fueled debate about the evolutionary forces countering their expansion. Purifying selection is thought to purge TE insertions from the genome, and TE sequences are targeted by hosts for epigenetic silencing. However, the interplay between epigenetic and evolutionary forces countering TE expansion remains unexplored. Here we analyze genomic, epigenetic, and population genetic data from Arabidopsis thaliana to yield three observations. First, gene expression is negatively correlated with the density of methylated TEs. Second, the signature of purifying selection is detectable for methylated TEs near genes but not for unmethylated TEs or for TEs far from genes. Third, TE insertions are distributed by age and methylation status, such that older, methylated TEs are farther from genes. Based on these observations, we present a model in which host silencing of TEs near genes has deleterious effects on neighboring gene expression, resulting in the preferential loss of methylated TEs from gene-rich chromosomal regions. This mechanism implies an evolutionary tradeoff in which the benefit of TE silencing imposes a fitness cost via deleterious effects on the expression of nearby genes.
    Genome Research 07/2009; 19(8):1419-28.