| 1. |
- Roy, Sushmita, et al.
(author)
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Identification of functional elements and regulatory circuits by Drosophila modENCODE.
- 2010
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In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6012, s. 1787-1797
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Journal article (peer-reviewed)abstract
- To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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| 2. |
- Rothman, Nathaniel, et al.
(author)
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A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 978-984
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Journal article (peer-reviewed)abstract
- We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.
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| 3. |
- Harrad, Stuart, et al.
(author)
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Indoor Contamination with Hexabromocyclododecanes, Polybrominated Diphenyl Ethers, and Perfluoroalkyl Compounds : An Important Exposure Pathway for People?
- 2010
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In: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 44:9, s. 3221-3231
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Research review (peer-reviewed)abstract
- This review underlines the importance of indoor contamination as a pathway of human exposure to hexabromocyclododecanes (HBCDs), polybrominated diphenyl ethers (PBDEs), and perfluoroalkyl compounds (PFCs). There is ample evidence of substantial contamination of indoor dust with these chemicals and that their concentrations in indoor air exceed substantially those outdoors. Studies examining the relationship between body burden and exposure via indoor dust are inconsistent while some indicate a link between body burdens and PBDE and HBCD exposure via dust ingestion, others find no correlation. Likewise, while concentrations in indoor dust and human tissues are both highly skewed, this does not necessarily imply causality. Evidence suggests exposure via dust ingestion is higher for toddlers than adults. Research priorities include identifying means of reducing indoor concentrations and indoor monitoring methods that provide the most ""biologically-relevant"" measures of exposure as well as monitoring a wider range of microenvironment categories. Other gaps include studies to improve understanding of the following: emission rates and mechanisms via which these contaminants migrate from products into indoor air and dust; relationships between indoor exposures and human body burdens; relevant physicochemical properties; the gastrointestinal uptake by humans of these chemicals from indoor dust; and human dust ingestion rates.
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