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Your search keyword '"Boyle, Evan A."' showing total 5 results
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5 results on '"Boyle, Evan A."'

1. Saturation editing of genomic regions by multiplex homology-directed repair

Author

Findlay, Gregory M., Boyle, Evan A., Hause, Ronald J., Klein, Jason C., and Shendure, Jay

Subjects
Research, Genetic research, Transcription (Genetics) -- Research, Genomics -- Research, Genetic transcription -- Research
Abstract

Functional consequences of genetic variants are best studied by manipulating the endogenous locus, which provides the native chromosomal context with respect to DNA sequence and epigenetic milieu, and for proteins, [...], Saturation mutagenesis (1, 2)--coupled to an appropriate biological assay--represents a fundamental means of achieving a high-resolution understanding of regulatory (3) and protein-coding (4) nucleic acid sequences of interest. However, mutagenized sequences introduced in trans on episomes or via random or 'safe-harbour' integration fail to capture the native context of the endogenous chromosomal locus (5). This shortcoming markedly limits the interpretability of the resulting measurements of mutational impact. Here, we couple CRISPR/ Cas9 RNA-guided cleavage (6) with multiplex homology-directed repair using a complex library of donor templates to demonstrate saturation editing of genomic regions. In exon 18 of BRCA1, we replace a six-base-pair (bp) genomic region with all possible hexamers, or the full exon with all possible single nucleotide variants (SNVs), and measure strong effects on transcript abundance attributable to nonsense-mediated decay and exonic splicing elements. We similarly perform saturation genome editing of a well-conserved coding region of an essential gene, DBR1, and measure relative effects on growth that correlate with functional impact. Measurement of the functional consequences of large numbers of mutations with saturation genome editing will potentially facilitate high-resolution functional dissection of both cis-regulatory elements and trans-acting factors, as well as the interpretation of variants of uncertain significance observed in clinical sequencing.

Published
2014

2. A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer

Author

Weren, Robbert D A, Ligtenberg, Marjolijn J L, Kets, C. Marleen, De Voer, Richarda M., Verwiel, Eugène T P, Spruijt, Liesbeth, Van Zelst-Stams, Wendy A G, Jongmans, Marjolijn C., Gilissen, Christian, Hehir-Kwa, Jayne Y., Hoischen, Alexander, Shendure, Jay, Boyle, Evan A., Kamping, Eveline J., Nagtegaal, Iris D., Tops, Bastiaan B J, Nagengast, Fokko M., Geurts Van Kessel, Ad, Van Krieken, J. Han J M, Kuiper, Roland P., Hoogerbrugge, Nicoline, Weren, Robbert D A, Ligtenberg, Marjolijn J L, Kets, C. Marleen, De Voer, Richarda M., Verwiel, Eugène T P, Spruijt, Liesbeth, Van Zelst-Stams, Wendy A G, Jongmans, Marjolijn C., Gilissen, Christian, Hehir-Kwa, Jayne Y., Hoischen, Alexander, Shendure, Jay, Boyle, Evan A., Kamping, Eveline J., Nagtegaal, Iris D., Tops, Bastiaan B J, Nagengast, Fokko M., Geurts Van Kessel, Ad, Van Krieken, J. Han J M, Kuiper, Roland P., and Hoogerbrugge, Nicoline

Published
2015

3. An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

Author

Wheway, Gabrielle, Schmidts, Miriam, Mans, Dorus A, Szymanska, Katarzyna, Nguyen, Thanh-Minh T, Racher, Hilary, Phelps, Ian G, Toedt, Grischa, Kennedy, Julie, Wunderlich, Kirsten A, Sorusch, Nasrin, Abdelhamed, Zakia A, Natarajan, Subaashini, Herridge, Warren, van Reeuwijk, Jeroen, Horn, Nicola, Boldt, Karsten, Parry, David A, Letteboer, Stef J F, Roosing, Susanne, Adams, Matthew, Bell, Sandra M, Bond, Jacquelyn, Higgins, Julie, Morrison, Ewan E, Tomlinson, Darren C, Slaats, Gisela G, van Dam, Teunis J P, Huang, Lijia, Kessler, Kristin, Giessl, Andreas, Logan, Clare V, Boyle, Evan A, Shendure, Jay, Anazi, Shamsa, Aldahmesh, Mohammed, Al Hazzaa, Selwa, Hegele, Robert A, Ober, Carole, Frosk, Patrick, Mhanni, Aizeddin A, Chodirker, Bernard N, Chudley, Albert E, Lamont, Ryan, Bernier, Francois P, Beaulieu, Chandree L, Gordon, Paul, Pon, Richard T, Donahue, Clem, Giles, Rachel H, UK10K Consortium, Wheway, Gabrielle, Schmidts, Miriam, Mans, Dorus A, Szymanska, Katarzyna, Nguyen, Thanh-Minh T, Racher, Hilary, Phelps, Ian G, Toedt, Grischa, Kennedy, Julie, Wunderlich, Kirsten A, Sorusch, Nasrin, Abdelhamed, Zakia A, Natarajan, Subaashini, Herridge, Warren, van Reeuwijk, Jeroen, Horn, Nicola, Boldt, Karsten, Parry, David A, Letteboer, Stef J F, Roosing, Susanne, Adams, Matthew, Bell, Sandra M, Bond, Jacquelyn, Higgins, Julie, Morrison, Ewan E, Tomlinson, Darren C, Slaats, Gisela G, van Dam, Teunis J P, Huang, Lijia, Kessler, Kristin, Giessl, Andreas, Logan, Clare V, Boyle, Evan A, Shendure, Jay, Anazi, Shamsa, Aldahmesh, Mohammed, Al Hazzaa, Selwa, Hegele, Robert A, Ober, Carole, Frosk, Patrick, Mhanni, Aizeddin A, Chodirker, Bernard N, Chudley, Albert E, Lamont, Ryan, Bernier, Francois P, Beaulieu, Chandree L, Gordon, Paul, Pon, Richard T, Donahue, Clem, Giles, Rachel H, and UK10K Consortium

Published
2015

4. A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer

Author

Genetica Sectie Oncogenetica, Weren, Robbert D A, Ligtenberg, Marjolijn J L, Kets, C. Marleen, De Voer, Richarda M., Verwiel, Eugène T P, Spruijt, Liesbeth, Van Zelst-Stams, Wendy A G, Jongmans, Marjolijn C., Gilissen, Christian, Hehir-Kwa, Jayne Y., Hoischen, Alexander, Shendure, Jay, Boyle, Evan A., Kamping, Eveline J., Nagtegaal, Iris D., Tops, Bastiaan B J, Nagengast, Fokko M., Geurts Van Kessel, Ad, Van Krieken, J. Han J M, Kuiper, Roland P., Hoogerbrugge, Nicoline, Genetica Sectie Oncogenetica, Weren, Robbert D A, Ligtenberg, Marjolijn J L, Kets, C. Marleen, De Voer, Richarda M., Verwiel, Eugène T P, Spruijt, Liesbeth, Van Zelst-Stams, Wendy A G, Jongmans, Marjolijn C., Gilissen, Christian, Hehir-Kwa, Jayne Y., Hoischen, Alexander, Shendure, Jay, Boyle, Evan A., Kamping, Eveline J., Nagtegaal, Iris D., Tops, Bastiaan B J, Nagengast, Fokko M., Geurts Van Kessel, Ad, Van Krieken, J. Han J M, Kuiper, Roland P., and Hoogerbrugge, Nicoline

Published
2015

5. An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

Author

Regenerative Medicine and Stem Cells, Nefro Vasculaire Geneeskunde, Circulatory Health, Wheway, Gabrielle, Schmidts, Miriam, Mans, Dorus A, Szymanska, Katarzyna, Nguyen, Thanh-Minh T, Racher, Hilary, Phelps, Ian G, Toedt, Grischa, Kennedy, Julie, Wunderlich, Kirsten A, Sorusch, Nasrin, Abdelhamed, Zakia A, Natarajan, Subaashini, Herridge, Warren, van Reeuwijk, Jeroen, Horn, Nicola, Boldt, Karsten, Parry, David A, Letteboer, Stef J F, Roosing, Susanne, Adams, Matthew, Bell, Sandra M, Bond, Jacquelyn, Higgins, Julie, Morrison, Ewan E, Tomlinson, Darren C, Slaats, Gisela G, van Dam, Teunis J P, Huang, Lijia, Kessler, Kristin, Giessl, Andreas, Logan, Clare V, Boyle, Evan A, Shendure, Jay, Anazi, Shamsa, Aldahmesh, Mohammed, Al Hazzaa, Selwa, Hegele, Robert A, Ober, Carole, Frosk, Patrick, Mhanni, Aizeddin A, Chodirker, Bernard N, Chudley, Albert E, Lamont, Ryan, Bernier, Francois P, Beaulieu, Chandree L, Gordon, Paul, Pon, Richard T, Donahue, Clem, Giles, Rachel H, UK10K Consortium, Regenerative Medicine and Stem Cells, Nefro Vasculaire Geneeskunde, Circulatory Health, Wheway, Gabrielle, Schmidts, Miriam, Mans, Dorus A, Szymanska, Katarzyna, Nguyen, Thanh-Minh T, Racher, Hilary, Phelps, Ian G, Toedt, Grischa, Kennedy, Julie, Wunderlich, Kirsten A, Sorusch, Nasrin, Abdelhamed, Zakia A, Natarajan, Subaashini, Herridge, Warren, van Reeuwijk, Jeroen, Horn, Nicola, Boldt, Karsten, Parry, David A, Letteboer, Stef J F, Roosing, Susanne, Adams, Matthew, Bell, Sandra M, Bond, Jacquelyn, Higgins, Julie, Morrison, Ewan E, Tomlinson, Darren C, Slaats, Gisela G, van Dam, Teunis J P, Huang, Lijia, Kessler, Kristin, Giessl, Andreas, Logan, Clare V, Boyle, Evan A, Shendure, Jay, Anazi, Shamsa, Aldahmesh, Mohammed, Al Hazzaa, Selwa, Hegele, Robert A, Ober, Carole, Frosk, Patrick, Mhanni, Aizeddin A, Chodirker, Bernard N, Chudley, Albert E, Lamont, Ryan, Bernier, Francois P, Beaulieu, Chandree L, Gordon, Paul, Pon, Richard T, Donahue, Clem, Giles, Rachel H, and UK10K Consortium

Published
2015

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