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Your search keyword '"Bohrson, Craig L."' showing total 19 results
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19 results on '"Bohrson, Craig L."'

2. Landmarks of human embryonic development inscribed in somatic mutations

Author

Bizzotto, Sara, Dou, Yanmei, Ganz, Javier, Doan, Ryan N, Kwon, Minseok, Bohrson, Craig L, Kim, Sonia N, Bae, Taejeong, Abyzov, Alexej, Network†, NIMH Brain Somatic Mosaicism, Park, Peter J, and Walsh, Christopher A

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Human Genome, Pediatric, Biotechnology, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research, 2.1 Biological and endogenous factors, Aetiology, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Adolescent, Adult, Cell Division, Cell Lineage, Clone Cells, Embryonic Development, Female, Gastrula, Gastrulation, Genetic Variation, Germ Layers, Humans, Male, Mutation, Neural Stem Cells, Neurons, Organogenesis, Polymorphism, Single Nucleotide, Prosencephalon, Single-Cell Analysis, Whole Genome Sequencing, NIMH Brain Somatic Mosaicism Network, General Science & Technology
Abstract

Although cell lineage information is fundamental to understanding organismal development, very little direct information is available for humans. We performed high-depth (250×) whole-genome sequencing of multiple tissues from three individuals to identify hundreds of somatic single-nucleotide variants (sSNVs). Using these variants as "endogenous barcodes" in single cells, we reconstructed early embryonic cell divisions. Targeted sequencing of clonal sSNVs in different organs (about 25,000×) and in more than 1000 cortical single cells, as well as single-nucleus RNA sequencing and single-nucleus assay for transposase-accessible chromatin sequencing of ~100,000 cortical single cells, demonstrated asymmetric contributions of early progenitors to extraembryonic tissues, distinct germ layers, and organs. Our data suggest onset of gastrulation at an effective progenitor pool of about 170 cells and about 50 to 100 founders for the forebrain. Thus, mosaic mutations provide a permanent record of human embryonic development at very high resolution.

Published
2021

3. Single-cell genome sequencing of human neurons identifies somatic point mutation and indel enrichment in regulatory elements

Author

Luquette, Lovelace J., Miller, Michael B., Zhou, Zinan, Bohrson, Craig L., Zhao, Yifan, Jin, Hu, Gulhan, Doga, Ganz, Javier, Bizzotto, Sara, Kirkham, Samantha, Hochepied, Tino, Libert, Claude, Galor, Alon, Kim, Junho, Lodato, Michael A., Garaycoechea, Juan I., Gawad, Charles, West, Jay, Walsh, Christopher A., and Park, Peter J.

Published
2022
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6. Mechanisms and therapeutic implications of hypermutation in gliomas

Author

Touat, Mehdi, Li, Yvonne Y., Boynton, Adam N., Spurr, Liam F., Iorgulescu, J. Bryan, Bohrson, Craig L., and Cortes-Ciriano, Isidro

Subjects
Antibody diversity -- Analysis, Temozolomide -- Dosage and administration -- Complications and side effects, Gliomas -- Drug therapy, DNA mismatch repair -- Analysis, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

A high tumour mutational burden (hypermutation) is observed in some gliomas.sup.1-5; however, the mechanisms by which hypermutation develops and whether it predicts the response to immunotherapy are poorly understood. Here we comprehensively analyse the molecular determinants of mutational burden and signatures in 10,294 gliomas. We delineate two main pathways to hypermutation: a de novo pathway associated with constitutional defects in DNA polymerase and mismatch repair (MMR) genes, and a more common post-treatment pathway, associated with acquired resistance driven by MMR defects in chemotherapy-sensitive gliomas that recur after treatment with the chemotherapy drug temozolomide. Experimentally, the mutational signature of post-treatment hypermutated gliomas was recapitulated by temozolomide-induced damage in cells with MMR deficiency. MMR-deficient gliomas were characterized by a lack of prominent T cell infiltrates, extensive intratumoral heterogeneity, poor patient survival and a low rate of response to PD-1 blockade. Moreover, although bulk analyses did not detect microsatellite instability in MMR-deficient gliomas, single-cell whole-genome sequencing analysis of post-treatment hypermutated glioma cells identified microsatellite mutations. These results show that chemotherapy can drive the acquisition of hypermutated populations without promoting a response to PD-1 blockade and supports the diagnostic use of mutational burden and signatures in cancer. Temozolomide therapy seems to lead to mismatch repair deficiency and hypermutation in gliomas, but not to an increase in response to immunotherapy., Author(s): Mehdi Touat [sup.1] [sup.2] [sup.3] , Yvonne Y. Li [sup.2] [sup.4] , Adam N. Boynton [sup.2] [sup.5] , Liam F. Spurr [sup.2] [sup.4] , J. Bryan Iorgulescu [sup.4] [sup.6] [...]

Published
2020
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11. Single-cell genome sequencing of human neurons identifies somatic point mutation and indel enrichment in regulatory elements

Author

Luquette, Lovelace J, Miller, Michael B, Zhou, Zinan, Bohrson, Craig L, Zhao, Yifan, Jin, Hu, Gulhan, Doga, Ganz, Javier, Bizzotto, Sara, Kirkham, Samantha, Hochepied, Tino, Libert, Claude, Galor, Alon, Kim, Junho, Lodato, Michael A, Garaycoechea, Juan I, Gawad, Charles, West, Jay, Walsh, Christopher A, Park, Peter J, Luquette, Lovelace J, Miller, Michael B, Zhou, Zinan, Bohrson, Craig L, Zhao, Yifan, Jin, Hu, Gulhan, Doga, Ganz, Javier, Bizzotto, Sara, Kirkham, Samantha, Hochepied, Tino, Libert, Claude, Galor, Alon, Kim, Junho, Lodato, Michael A, Garaycoechea, Juan I, Gawad, Charles, West, Jay, Walsh, Christopher A, and Park, Peter J

Abstract

Accurate somatic mutation detection from single-cell DNA sequencing is challenging due to amplification-related artifacts. To reduce this artifact burden, an improved amplification technique, primary template-directed amplification (PTA), was recently introduced. We analyzed whole-genome sequencing data from 52 PTA-amplified single neurons using SCAN2, a new genotyper we developed to leverage mutation signatures and allele balance in identifying somatic single-nucleotide variants (SNVs) and small insertions and deletions (indels) in PTA data. Our analysis confirms an increase in nonclonal somatic mutation in single neurons with age, but revises the estimated rate of this accumulation to 16 SNVs per year. We also identify artifacts in other amplification methods. Most importantly, we show that somatic indels increase by at least three per year per neuron and are enriched in functional regions of the genome such as enhancers and promoters. Our data suggest that indels in gene-regulatory elements have a considerable effect on genome integrity in human neurons.

Published
2022

12. Single-cell genome sequencing of human neurons identifies somatic point mutation and indel enrichment in regulatory elements

Author

Hubrecht Institute with UMC, Luquette, Lovelace J., Miller, Michael B., Zhou, Zinan, Bohrson, Craig L., Zhao, Yifan, Jin, Hu, Gulhan, Doga, Ganz, Javier, Bizzotto, Sara, Kirkham, Samantha, Hochepied, Tino, Libert, Claude, Galor, Alon, Kim, Junho, Lodato, Michael A., Garaycoechea, Juan I., Gawad, Charles, West, Jay, Walsh, Christopher A., Park, Peter J., Hubrecht Institute with UMC, Luquette, Lovelace J., Miller, Michael B., Zhou, Zinan, Bohrson, Craig L., Zhao, Yifan, Jin, Hu, Gulhan, Doga, Ganz, Javier, Bizzotto, Sara, Kirkham, Samantha, Hochepied, Tino, Libert, Claude, Galor, Alon, Kim, Junho, Lodato, Michael A., Garaycoechea, Juan I., Gawad, Charles, West, Jay, Walsh, Christopher A., and Park, Peter J.

Published
2022

13. Gibbon genome and the fast karyotype evolution of small apes

Author

Carbone, Lucia, Alan Harris, R., Gnerre, Sante, Veeramah, Krishna R., Lorente-Galdos, Belen, Huddleston, John, Meyer, Thomas J., Herrero, Javier, Roos, Christian, Aken, Bronwen, Anaclerio, Fabio, Archidiacono, Nicoletta, Baker, Carl, Barrell, Daniel, Batzer, Mark A., Beal, Kathryn, Blancher, Antoine, Bohrson, Craig L., Brameier, Markus, Campbell, Michael S., Capozzi, Oronzo, Casola, Claudio, Chiatante, Giorgia, Cree, Andrew, Damert, Annette, de Jong, Pieter J., Dumas, Laura, Fernandez-Callejo, Marcos, Flicek, Paul, Fuchs, Nina V., Gut, Ivo, Gut, Marta, Hahn, Matthew W., Hernandez-Rodriguez, Jessica, Hillier, LaDeana W., Hubley, Robert, Ianc, Bianca, Izsvák, Zsuzsanna, Jablonski, Nina G., Johnstone, Laurel M., Karimpour-Fard, Anis, Konkel, Miriam K., Kostka, Dennis, Lazar, Nathan H., Lee, Sandra L., Lewis, Lora R., Liu, Yue, Locke, Devin P., Mallick, Swapan, Mendez, Fernando L., Muffato, Matthieu, Nazareth, Lynne V., Nevonen, Kimberly A., O’Bleness, Majesta, Ochis, Cornelia, Odom, Duncan T., Pollard, Katherine S., Quilez, Javier, Reich, David, Rocchi, Mariano, Schumann, Gerald G., Searle, Stephen, Sikela, James M., Skollar, Gabriella, Smit, Arian, Sonmez, Kemal, Hallers, Boudewijn ten, Terhune, Elizabeth, Thomas, Gregg W. C., Ullmer, Brygg, Ventura, Mario, Walker, Jerilyn A., Wall, Jeffrey D., Walter, Lutz, Ward, Michelle C., Wheelan, Sarah J., Whelan, Christopher W., White, Simon, Wilhelm, Larry J., Woerner, August E., Yandell, Mark, Zhu, Baoli, Hammer, Michael F., Marques-Bonet, Tomas, Eichler, Evan E., Fulton, Lucinda, Fronick, Catrina, Muzny, Donna M., Warren, Wesley C., Worley, Kim C., Rogers, Jeffrey, Wilson, Richard K., and Gibbs, Richard A.

Published
2014
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15. Abstract 5705: Mechanisms and therapeutic implications of hypermutation in gliomas

Author

Touat, Mehdi, primary, Li, Yvonne Y., additional, Boynton, Adam N., additional, Spurr, Liam F., additional, Iorgulescu, Bryan, additional, Bohrson, Craig L., additional, Cortes-Ciriano, Isidro, additional, Geduldig, Jack E., additional, Pelton, Kristine, additional, Lim-Fat, Mary J., additional, Pal, Sangita, additional, Ramkissoon, Shakti H., additional, Dubois, Frank, additional, Bellamy, Charlotte, additional, Currimjee, Naomi, additional, Qian, Kenin, additional, Malinowski, Seth, additional, Shetty, Aniket, additional, Chow, Kin-Hoe, additional, Verreault, Maïté, additional, Guillerm, Erell, additional, Ammari, Samy, additional, Beuvon, Frédéric, additional, Mokhtari, Karima, additional, Alentorn, Agusti, additional, Dehais, Caroline, additional, Houillier, Caroline, additional, Laigle-Donadey, Florence, additional, Psimaras, Dimitri, additional, Carpentier, Alexandre, additional, Cornu, Philippe, additional, Capelle, Laurent, additional, Mathon, Bertrand, additional, Barnholtz-Sloan, Jill S., additional, Chakravarti, Arnab, additional, Bi, Wenya L., additional, Frampton, Garrett M., additional, Sanson, Marc, additional, Alexander, Brian M., additional, Cherniack, Andrew, additional, Wen, Patrick Y., additional, Reardon, David A., additional, Marabelle, Aurelien, additional, Park, Peter J., additional, Idbaih, Ahmed, additional, Beroukhim, Rameen, additional, Bandopadhayay, Pratiti, additional, Bielle, Franck, additional, and Ligon, Keith L., additional

Published
2020
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16. Aging and neurodegeneration are associated with increased mutations in single human neurons

Author

Lodato, Michael A., primary, Rodin, Rachel E., additional, Bohrson, Craig L., additional, Coulter, Michael E., additional, Barton, Alison R., additional, Kwon, Minseok, additional, Sherman, Maxwell A., additional, Vitzthum, Carl M., additional, Luquette, Lovelace J., additional, Yandava, Chandri, additional, Yang, Pengwei, additional, Chittenden, Thomas W., additional, Hatem, Nicole E., additional, Ryu, Steven C., additional, Woodworth, Mollie B., additional, Park, Peter J., additional, and Walsh, Christopher A., additional

Published
2017
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17. Linked-read analysis identifies mutations in single cell DNA sequencing data

Author

Bohrson, Craig L., primary, Barton, Allison R., additional, Lodato, Michael A., additional, Rodin, Rachel E., additional, Viswanadham, Vinay, additional, Gulhan, Doga, additional, Cortes, Isidro, additional, Sherman, Maxwell A., additional, Luquette, Lovelace J., additional, Kwon, Minseok, additional, Coulter, Michael E., additional, Walsh, Christopher A., additional, and Park, Peter J., additional

Published
2017
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18. Author Correction: The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing

Author

Rodin, Rachel E., Dou, Yanmei, Kwon, Minseok, Sherman, Maxwell A., D’Gama, Alissa M., Doan, Ryan N., Rento, Lariza M., Girskis, Kelly M., Bohrson, Craig L., Kim, Sonia N., Nadig, Ajay, Luquette, Lovelace J., Gulhan, Doga C., Park, Peter J., and Walsh, Christopher A.

Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41593-021-00830-8.

Published
2021
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19. Contrasting patterns of somatic mutations in neurons and glia reveal differential predisposition to disease in the aging human brain.

Author

Ganz J, Luquette LJ, Bizzotto S, Bohrson CL, Jin H, Miller MB, Zhou Z, Galor A, Park PJ, and Walsh CA

Abstract

Characterizing the mechanisms of somatic mutations in the brain is important for understanding aging and disease, but little is known about the mutational patterns of different cell types. We performed whole-genome sequencing of 71 oligodendrocytes and 51 neurons from neurotypical individuals (0.4 to 104 years old) and identified >67,000 somatic single nucleotide variants (sSNVs) and small insertions and deletions (indels). While both cell types accumulate mutations with age, oligodendrocytes accumulate sSNVs 69% faster than neurons (27/year versus 16/year) whereas indels accumulate 42% slower (1.8/year versus 3.1/year). Correlation with single-cell RNA and chromatin accessibility from the same brains revealed that oligodendrocyte mutations are enriched in inactive genomic regions and are distributed similarly to mutations in brain cancers. In contrast, neuronal mutations are enriched in open, transcriptionally active chromatin. These patterns highlight differences in the mutagenic processes in glia and neurons and suggest cell type-specific, age-related contributions to neurodegeneration and oncogenesis.

Published
2023
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