The implications of ENCODE for diagnostics

Fratkin, Eugene; Bercovici, Sivan; Stephan, Dietrich A.

doi:10.1038/nbt.2418

Cited by 13 publications

(9 citation statements)

References 5 publications

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“…Genome-wide analyses of chromatin status and transcription factor binding in various tissues have revealed that 80% of the genome exert functional role [151,152,178]. ENCODE [150,151] high throughput large scale coordinated analyses thus enable to survey potential functional sites at any locus and usefully complement targeted studies aimed at characterizing the roles of cis -elements and trans -acting factors involved at different steps controlling the developmental regulation of gene expression.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the functional SLC11A1 polymorphism 274C/T carried by exon 3 and which affects host resistance to pediatric TB (Section 3.2) lies about 150 bp downstream this predicted regulatory element. It has been estimated that 99% of human genome lies within 1.7 kb from ENCODE-defined functional elements [150,151,152,178]. The relative proximity of SLC11A1 polymorphism 274C/T with the predicted functional element corresponding to Footprint #8 (Figure 4A ,B) that is part of a chromatin domain apparently active in terminally differentiated CD14 + cells, may thus suggest that this SLC11A1 polymorphism might influence regulation of transcription.…”

Section: Delineation Of Slc11a1 Distal Elements Mobilized During Mmentioning

confidence: 99%

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Cell-Type Specific Determinants of NRAMP1 Expression in Professional Phagocytes

Cellier

2013

Biology

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The Natural resistance-associated macrophage protein 1 (Nramp1 or Solute carrier 11 member 1, Slc11a1) transports divalent metals across the membrane of late endosomes and lysosomes in professional phagocytes. Nramp1 represents an ancient eukaryotic cell-autonomous defense whereas the gene duplication that yielded Nramp1 and Nramp2 predated the origin of Sarcopterygians (lobe-finned fishes and tetrapods). SLC11A1 genetic polymorphisms associated with human resistance to tuberculosis consist of potential regulatory variants. Herein, current knowledge of the regulation of SLC11A1 gene expression is reviewed and comprehensive analysis of ENCODE data available for hematopoietic cell-types suggests a hypothesis for the regulation of SLC11A1 expression during myeloid development and phagocyte functional polarization. SLC11A1 is part of a 34.6 kb CTCF-insulated locus scattered with predicted regulatory elements: a 3' enhancer, a large 5' enhancer domain and four elements spread around the transcription start site (TSS), including several C/EBP and PU.1 sites. SLC11A1 locus ends appear mobilized by ETS-related factors early during myelopoiesis; activation of both 5' and 3' enhancers in myelo-monocytic cells correlate with transcription factor binding at the TSS. Characterizing the corresponding cis/trans determinants functionally will establish the mechanisms involved and possibly reveal genetic variation that impacts susceptibility to infectious or immune diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Delineation Of Slc11a1 Distal Elements Mobilized During Mmentioning

confidence: 99%

Cell-Type Specific Determinants of NRAMP1 Expression in Professional Phagocytes

Cellier

2013

Biology

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“…Epigenomic reprogramming has a clearcut role in cancer, be it via transcription factors or chromatin regulators (Dawson and Kouzarides, 2012, Suva et al, 2013). Although access to tissue to define epigenomic signatures is a limiting factor outside of the cancer space, it is apparent that many other diseases are affected by epigenomic dynamics, such as complications of diabetes, rheumatoid arthritis or hypertension (Pirola et al, 2010, Liu et al, 2013, Fratkin et al, 2012). Furthermore, epigenomic changes affect susceptibility to diseases, as has been shown with open chromatin related to the TCF7L2 gene (Groop, 2010) and parental origin of sequence variants for Type 2 diabetes mellitus, breast and prostate cancer (Kong et al, 2009).…”

Section: The Omic Toolsmentioning

confidence: 99%

Individualized Medicine from Prewomb to Tomb

Topol

2014

Cell

270

217

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That each of us is truly biologically unique, extending to even monozygotic, “identical” twins, is not fully appreciated. Now that it is possible to perform a comprehensive “omic” assessment of an individual, including one's DNA and RNA sequence, and at least some characterization of one's proteome, metabolome, microbiome, autoantibodies, and epigenome, it has become abundantly clear that each of us has truly one-of-a-kind biological content. Well beyond the allure of the matchless fingerprint or snowflake concept, these singular, individual data and information set up a remarkable and unprecedented opportunity to improve medical treatment and develop preventive strategies to preserve health.

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“…WGS allows the identification of gene copy numbers and rearrangements, and changes in noncoding regions that impact transcription regulation [19,20]. WGS remains expensive, as high redundancy coverage is needed in oncology because of the dilution of tumor cells by stromal cells as well as genetic heterogeneity.…”

Section: The Different Types Of Genome Sequencingmentioning

confidence: 99%

Impact of tumor sequencing on the use of anticancer drugs

Thomas

Desmedt²,

Aftimos³

et al. 2014

Current Opinion in Oncology

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NGS and other molecular technologies are transforming the practice of medical oncology and clinical research. Sequencing of primary tumors, metastases, or blood-derived circulating tumor DNA has great potential to guide individualized cancer treatment. However, the integration of NGS as a breakthrough technology is associated with operational challenges such as information processing, medical education and interpretation, and reimbursement.

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The implications of ENCODE for diagnostics

Cited by 13 publications

References 5 publications

Cell-Type Specific Determinants of NRAMP1 Expression in Professional Phagocytes

Cell-Type Specific Determinants of NRAMP1 Expression in Professional Phagocytes

Individualized Medicine from Prewomb to Tomb

Impact of tumor sequencing on the use of anticancer drugs

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