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Research: Restless Legs Syndrome-associated intronic common variant in Meis1 alters enhancer function in the developing telencephalon
- Derek Spieler,
- Maria Kaffe,
- Franziska Knauf,
- José Bessa,
- Juan J. Tena,
- Florian Giesert,
- Barbara Schormair,
- Erik Tilch,
- Heekyoung Lee,
- Marion Horsch,
- Darina Czamara,
- Nazanin Karbalai,
- Christine von Toerne,
- Melanie Waldenberger,
- Christian Gieger,
- Peter Lichtner,
- Melina Claussnitzer,
- Ronald Naumann,
- Bertram Müller-Myhsok,
- Miguel Torres,
- Lillian Garrett,
- Jan Rozman,
- Martin Klingenspor,
- Valérie Gailus-Durner,
- Helmut Fuchs,
- Martin Hrabě de Angelis,
- Johannes Beckers,
- Sabine M. Hölter,
- Thomas Meitinger,
- Stefanie M. Hauck,
- Helmut Laumen,
- Wolfgang Wurst,
- Fernando Casares,
- Jose Luis Gómez-Skarmeta,
- and Juliane Winkelmann
Genome Res. April 2014 24: 592-603; Published in Advance March 18, 2014, doi:10.1101/gr.166751.113
...variants in strong LD map to clusters of enhancers, which cooperatively affect gene expression and thus confer concerted susceptibility to disease (Corradin et al. 2014). Given our results, such modular organization with multiple enhancers next to the identified enhancer HCNR 617 might play a role...
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Method: Ultrafast genome-wide scan for SNP–SNP interactions in common complex disease
- Snehit Prabhu and
- Itsik Pe'er
Genome Res. November 2012 22: 2230-2240; Published in Advance July 5, 2012, doi:10.1101/gr.137885.112
...to find long-range interactions in common diseases using a standard two-locus test that contrasts the linkage disequilibrium between SNPs in cases and controls. Our ultrafast method overcomes the computational burden of a genome × genome scan by using a novel randomization technique that requires 10...
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Research: Enhancers and super-enhancers have an equivalent regulatory role in embryonic stem cells through regulation of single or multiple genes
- Sakthi D. Moorthy,
- Scott Davidson,
- Virlana M. Shchuka,
- Gurdeep Singh,
- Nakisa Malek-Gilani,
- Lida Langroudi,
- Alexandre Martchenko,
- Vincent So,
- Neil N. Macpherson,
- and Jennifer A. Mitchell
Genome Res. February 2017 27: 246-258; Published in Advance November 28, 2016, doi:10.1101/gr.210930.116
...revealed that each of the EC(Med13l) regions contained an active enhancer (Supplemental Fig. S5). These data suggest that partial redundancy in enhancer function may be a common feature in the regulation of genes controlled by multiple enhancers; however, these data also reveal the ability of each enhancer...
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Method: Whole-genome analysis of noncoding genetic variations identifies multiscale regulatory element perturbations associated with Hirschsprung disease
- Alexander Xi Fu,
- Kathy Nga-Chu Lui,
- Clara Sze-Man Tang,
- Ray Kit Ng,
- Frank Pui-Ling Lai,
- Sin-Ting Lau,
- Zhixin Li,
- Maria-Mercè Garcia-Barcelo,
- Pak-Chung Sham,
- Paul Kwong-Hang Tam,
- Elly Sau-Wai Ngan,
- and Kevin Y. Yip
Genome Res. November 2020 30: 1618-1632; Published in Advance September 18, 2020, doi:10.1101/gr.264473.120
...be many times that of coding variants; many of them are not functional but in linkage disequilibrium with the functional ones; different variants can have epistatic effects; different variants can affect the same genes or pathways in different individuals; and some variants are related to each other...
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Method: Massively parallel quantification of the regulatory effects of noncoding genetic variation in a human cohort
- Christopher M. Vockley,
- Cong Guo,
- William H. Majoros,
- Michael Nodzenski,
- Denise M. Scholtens,
- M. Geoffrey Hayes,
- William L. Lowe, Jr.,
- and Timothy E. Reddy
Genome Res. August 2015 25: 1206-1214; Published in Advance June 17, 2015, doi:10.1101/gr.190090.115
...of amino acid substitutions and indels. PLoS One 7: e46688. ↵Corradin O, Saiakhova A, Akhtar-Zaidi B, Myeroff L, Willis J, Cowper-Sal-lari R, Lupien M, Markowitz S, Scacheri PC. 2014. Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer...
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Perspective: Genomic approaches for understanding the genetics of complex disease
- William L. Lowe, Jr. and
- Timothy E. Reddy
Genome Res. October 2015 25: 1432-1441; doi:10.1101/gr.190603.115
..., Akhtar-Zaidi B, Myeroff L,Willis J, Cowper-Sal lari R, Lupien M, Markowitz S, Scacheri PC. 2014. Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits. Genome Res 24: 1–13. de Bruin C, Dauber A. 2015...
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Research: New guidelines for DNA methylome studies regarding 5-hydroxymethylcytosine for understanding transcriptional regulation
- Le Li,
- Yuwei Gao,
- Qiong Wu,
- Alfred S.L. Cheng,
- and Kevin Y. Yip
Genome Res. April 2019 29: 543-553; Published in Advance February 19, 2019, doi:10.1101/gr.240036.118
...differential methylation in cancer that correlates with differential gene expression (Irizarry et al. 2009). DNA methylation at regulatory elements other than promoters is less studied, but some recent work has started to show correlations between enhancer methylation and gene silencing (Aran et al. 2013; Heyn...
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Method: Models of human core transcriptional regulatory circuitries
- Violaine Saint-André,
- Alexander J. Federation,
- Charles Y. Lin,
- Brian J. Abraham,
- Jessica Reddy,
- Tong Ihn Lee,
- James E. Bradner,
- and Richard A. Young
Genome Res. March 2016 26: 385-396; Published in Advance February 3, 2016, doi:10.1101/gr.197590.115
.... Semin Cell Dev Biol 22: 729–734. Corradin O, Saiakhova A, Akhtar-Zaidi B, Myeroff L,Willis J, Cowper-Sal lari R, Lupien M, Markowitz S, Scacheri PC. 2014. Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common...
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Method: FIND: difFerential chromatin INteractions Detection using a spatial Poisson process
- Mohamed Nadhir Djekidel,
- Yang Chen,
- and Michael Q. Zhang
Genome Res. March 2018 28: 412-422; Published in Advance February 12, 2018, doi:10.1101/gr.212241.116
...disequilibrium dictate levels of gene expression to confer susceptibility to common traits. Genome Res 24: 1–13. ↵Dekker J, Belmont AS, Guttman M, Leshyk VO, Lis JT, Lomvardas S, Mirny LA, O'Shea CC, Park PJ, Ren B, et al. 2017. The 4D nucleome project. Nature 549: 219–226. ↵Dixon JR, Jung I, Selvaraj S, Shen Y...
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