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Title: Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

Abstract

Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and their contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetricallymore » to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

Authors:
 [1];  [2];  [3];  [2]; ORCiD logo [4];  [2];  [5];  [2];  [2];  [2];  [2];  [2];  [2];  [2];  [2];  [6];  [7];  [8];  [9];  [10] more »;  [11];  [12];  [13];  [14];  [15];  [16];  [17];  [18];  [19];  [20];  [21];  [22];  [23];  [24];  [25];  [16];  [26];  [2];  [2];  [2];  [2] « less
+ Show Author Affiliations
  1. Wellcome Trust Sanger Institute, Hinxton (United Kingdom); Korea Advanced Institute of Science and Technology, Daejeon (Republic of Korea)
  2. Wellcome Trust Sanger Institute, Hinxton (United Kingdom)
  3. Wellcome Trust Sanger Institute, Hinxton (United Kingdom); European Bioinformatics Institute, Hinxton (United Kingdom)
  4. Wellcome Trust Sanger Institute, Hinxton (United Kingdom); Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  5. Wellcome Trust Sanger Institute, Hinxton (United Kingdom); Wellcome Trust Centre for Human Genetics, Oxford (United Kingdom)
  6. Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
  7. Univ. of Oslo, Lorenskog (Norway)
  8. King's College London School of Medicine, London (United Kindgom)
  9. Ninewells Hospital and Medicine School, Dundee (United Kingdom)
  10. BioCare, Lund (Sweden); CREATE Health, Lund (Sweden); Lund Univ., Lund (Sweden)
  11. Radboud Univ. Medical Center, Nijmegen (The Netherlands)
  12. Academic Medical Center, Amsterdam (The Netherlands)
  13. Singapore General Hospital (Singapore)
  14. Univ. of Cambridge, Cambridge (United Kingdom)
  15. King's College London, London (United Kingdom); Institute of Cancer Research, London (United Kingdom)
  16. The Univ. of Texas MD Anderson Cancer Center, Houston, TX (United States)
  17. Univ. of California, San Francisco, CA (United States)
  18. Erasmus Univ. Medical Center, Rotterdam (Netherlands)
  19. Institut Jules Bordet, Brussels (Belgium)
  20. Univ. of Bergen, Bergen (Norway); Haukeland Univ. Hospital, Bergen (Norway)
  21. Radboud Univ. Medical Center, Nijmegen (Netherlands)
  22. Univ. of Queensland, Brisbane (Australia); Royal Brisbane and Women's Hospital, Brisbane (Australia)
  23. Univ. of Iceland, Reykjavik (Iceland)
  24. Oslo Univ. Hospital, The Norwegian Radium Hospital, Oslo (Norway); Univ. of Oslo, Oslo (Norway)
  25. Johns Hopkins Medicine, Washington, D.C. (United States)
  26. Centre Leon Berard, Lyon Cedex (France)
Publication Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE Laboratory Directed Research and Development (LDRD) Program
OSTI Identifier:
1356130
Report Number(s):
LA-UR-16-20126
Journal ID: ISSN 0028-0836
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Accepted Manuscript
Journal Name:
Nature (London)
Additional Journal Information:
Journal Name: Nature (London); Journal Volume: 543; Journal Issue: 7647; Journal ID: ISSN 0028-0836
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; Biological Science

Citation Formats

Ju, Young Seok, Martincorena, Inigo, Gerstung, Moritz, Petljak, Mia, Alexandrov, Ludmil B., Rahbari, Raheleh, Wedge, David C., Davies, Helen R., Ramakrishna, Manasa, Fullam, Anthony, Martin, Sancha, Alder, Christopher, Patel, Nikita, Gamble, Steve, O’Meara, Sarah, Giri, Dilip D., Sauer, Torril, Pinder, Sarah E., Purdie, Colin A., Borg, Åke, Stunnenberg, Henk, van de Vijver, Marc, Tan, Benita K. T., Caldas, Carlos, Tutt, Andrew, Ueno, Naoto T., van ’t Veer, Laura J., Martens, John W. M., Sotiriou, Christos, Knappskog, Stian, Span, Paul N., Lakhani, Sunil R., Eyfjörd, Jórunn Erla, Børresen-Dale, Anne-Lise, Richardson, Andrea, Thompson, Alastair M., Viari, Alain, Hurles, Matthew E., Nik-Zainal, Serena, Campbell, Peter J., and Stratton, Michael R. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo. United States: N. p., 2017. Web. doi:10.1038/nature21703.
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Ju, Young Seok, Martincorena, Inigo, Gerstung, Moritz, Petljak, Mia, Alexandrov, Ludmil B., Rahbari, Raheleh, Wedge, David C., Davies, Helen R., Ramakrishna, Manasa, Fullam, Anthony, Martin, Sancha, Alder, Christopher, Patel, Nikita, Gamble, Steve, O’Meara, Sarah, Giri, Dilip D., Sauer, Torril, Pinder, Sarah E., Purdie, Colin A., Borg, Åke, Stunnenberg, Henk, van de Vijver, Marc, Tan, Benita K. T., Caldas, Carlos, Tutt, Andrew, Ueno, Naoto T., van ’t Veer, Laura J., Martens, John W. M., Sotiriou, Christos, Knappskog, Stian, Span, Paul N., Lakhani, Sunil R., Eyfjörd, Jórunn Erla, Børresen-Dale, Anne-Lise, Richardson, Andrea, Thompson, Alastair M., Viari, Alain, Hurles, Matthew E., Nik-Zainal, Serena, Campbell, Peter J., & Stratton, Michael R. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo. United States. https://doi.org/10.1038/nature21703
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Ju, Young Seok, Martincorena, Inigo, Gerstung, Moritz, Petljak, Mia, Alexandrov, Ludmil B., Rahbari, Raheleh, Wedge, David C., Davies, Helen R., Ramakrishna, Manasa, Fullam, Anthony, Martin, Sancha, Alder, Christopher, Patel, Nikita, Gamble, Steve, O’Meara, Sarah, Giri, Dilip D., Sauer, Torril, Pinder, Sarah E., Purdie, Colin A., Borg, Åke, Stunnenberg, Henk, van de Vijver, Marc, Tan, Benita K. T., Caldas, Carlos, Tutt, Andrew, Ueno, Naoto T., van ’t Veer, Laura J., Martens, John W. M., Sotiriou, Christos, Knappskog, Stian, Span, Paul N., Lakhani, Sunil R., Eyfjörd, Jórunn Erla, Børresen-Dale, Anne-Lise, Richardson, Andrea, Thompson, Alastair M., Viari, Alain, Hurles, Matthew E., Nik-Zainal, Serena, Campbell, Peter J., and Stratton, Michael R. Wed . "Somatic mutations reveal asymmetric cellular dynamics in the early human embryo". United States. https://doi.org/10.1038/nature21703. https://www.osti.gov/servlets/purl/1356130.
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@article{osti_1356130,
title = {Somatic mutations reveal asymmetric cellular dynamics in the early human embryo},
author = {Ju, Young Seok and Martincorena, Inigo and Gerstung, Moritz and Petljak, Mia and Alexandrov, Ludmil B. and Rahbari, Raheleh and Wedge, David C. and Davies, Helen R. and Ramakrishna, Manasa and Fullam, Anthony and Martin, Sancha and Alder, Christopher and Patel, Nikita and Gamble, Steve and O’Meara, Sarah and Giri, Dilip D. and Sauer, Torril and Pinder, Sarah E. and Purdie, Colin A. and Borg, Åke and Stunnenberg, Henk and van de Vijver, Marc and Tan, Benita K. T. and Caldas, Carlos and Tutt, Andrew and Ueno, Naoto T. and van ’t Veer, Laura J. and Martens, John W. M. and Sotiriou, Christos and Knappskog, Stian and Span, Paul N. and Lakhani, Sunil R. and Eyfjörd, Jórunn Erla and Børresen-Dale, Anne-Lise and Richardson, Andrea and Thompson, Alastair M. and Viari, Alain and Hurles, Matthew E. and Nik-Zainal, Serena and Campbell, Peter J. and Stratton, Michael R.},
abstractNote = {Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and their contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.},
doi = {10.1038/nature21703},
journal = {Nature (London)},
number = 7647,
volume = 543,
place = {United States},
year = {Wed Mar 22 00:00:00 EDT 2017},
month = {Wed Mar 22 00:00:00 EDT 2017}
}
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Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis
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Age-related mutations associated with clonal hematopoietic expansion and malignancies
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Genetic Mosaics and the Germ Line Lineage
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Landscape of somatic mutations in 560 breast cancer whole-genome sequences.
journalarticle, January 2016

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  • Rahbari, Raheleh; Wuster, Arthur; Lindsay, Sarah J.
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The Life History of 21 Breast Cancers
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Developmental Plasticity Is Bound by Pluripotency and the Fgf and Wnt Signaling Pathways
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Chromosome Instability Is Common in Human Cleavage-Stage Embryos
journal, January 2012

Production of viable chicken by allogeneic transplantation of primordial germ cells induced from somatic cells
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The Sequence Alignment/Map format and SAMtools
journal, June 2009

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journal, October 2014

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Recent advances in the study of somatic mosaicism and diseases other than cancer
journal, June 2014

Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis
journal, April 2014

Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer.
text, January 2014

  • Ju, Young Seok; Alexandrov, Ludmil B.; Gerstung, Moritz
  • Apollo - University of Cambridge Repository
  • DOI: 10.17863/cam.31876

The human blastocyst: cell number, death and allocation during late preimplantation development in vitro
journal, November 1989

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  • DOI: 10.1242/dev.107.3.597
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    Somatic Mutations and Clonal Hematopoiesis: Unexpected Potential New Drivers of Age-Related Cardiovascular Disease
    journal, February 2018

    The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils.
    journalarticle, January 2018

    • Stammnitz, Maximilian R.; Coorens, Tim HH; Gori, Kevin C.
    • Elsevier BV
    • DOI: 10.17863/cam.21016

    Cell competition: the winners and losers of fitness selection
    journal, July 2019

    • Bowling, Sarah; Lawlor, Katerina; Rodríguez, Tristan A.
    • Development, Vol. 146, Issue 13
    • DOI: 10.1242/dev.167486

    Entanglement of Genetics and Epigenetics in Parkinson’s Disease
    journal, March 2019

    Aging and the rise of somatic cancer-associated mutations in normal tissues
    journal, January 2018

    Mapping human development at single-cell resolution
    journal, February 2018

    • Behjati, Sam; Lindsay, Susan; Teichmann, Sarah A.
    • Development, Vol. 145, Issue 3
    • DOI: 10.1242/dev.152561

    Human glioblastoma arises from subventricular zone cells with low-level driver mutations
    journal, August 2018

    Single-cell lineage tracing by integrating CRISPR-Cas9 mutations with transcriptomic data
    journal, June 2020

    Replicative cellular age distributions in compartmentalized tissues
    journal, August 2018

    • Böttcher, Marvin A.; Dingli, David; Werner, Benjamin
    • Journal of The Royal Society Interface, Vol. 15, Issue 145
    • DOI: 10.1098/rsif.2018.0272

    Concordance for clonal hematopoiesis is limited in elderly twins.
    text, January 2020

    • Fabre, Margarete A.; McKerrell, Thomas; Zwiebel, Maximillian
    • Apollo - University of Cambridge Repository
    • DOI: 10.17863/cam.47095

    The genome-wide landscape of C:G > T:A polymorphism at the CpG contexts in the human population
    journal, March 2020

    Novel Insights Into the NLRP3 Inflammasome in Atherosclerosis
    journal, June 2019

    Frequency and signature of somatic variants in 1461 human brain exomes.
    journalarticle, January 2019

    A clinical survey of mosaic single nucleotide variants in disease-causing genes detected by exome sequencing
    journal, July 2019

    Robust identification of mosaic variants in congenital heart disease
    journal, February 2018

    Error-prone bypass of DNA lesions during lagging-strand replication is a common source of germline and cancer mutations
    journal, December 2018

    • Seplyarskiy, Vladimir B.; Akkuratov, Evgeny E.; Akkuratova, Natalia
    • Nature Genetics, Vol. 51, Issue 1
    • DOI: 10.1038/s41588-018-0285-7

    Error-prone bypass of DNA lesions during lagging strand replication is a common source of germline and cancer mutations
    posted_content, May 2018

    • Seplyarskiy, Vladimir B.; Akkuratov, Evgeny E.; Akkuratova, Natalia V.
    • Nature Genetics
    • DOI: 10.1101/200691

    Early divergence of mutational processes in human fetal tissues
    journal, May 2019

    • Kuijk, Ewart; Blokzijl, Francis; Jager, Myrthe
    • Science Advances, Vol. 5, Issue 5
    • DOI: 10.1126/sciadv.aaw1271

    Development of the variant calling algorithm, ADIScan, and its use to estimate discordant sequences between monozygotic twins
    journal, June 2018

    • Cho, Yangrae; Lee, Sunho; Hong, Jong Hui
    • Nucleic Acids Research, Vol. 46, Issue 15
    • DOI: 10.1093/nar/gky445

    Signatures of replication timing, recombination and sex in the spectrum of rare variants on the human X chromosome and autosomes
    posted_content, May 2019

    • Agarwal, Ipsita; Przeworski, Molly
    • Proceedings of the National Academy of Sciences
    • DOI: 10.1101/519421

    Genomic mosaicism in paternal sperm and multiple parental tissues in a Dravet syndrome cohort
    journal, November 2017

    Tracing the origin of heterogeneity and symmetry breaking in the early mammalian embryo
    journal, May 2018

    Signatures of replication timing, recombination, and sex in the spectrum of rare variants on the human X chromosome and autosomes
    journal, August 2019

    • Agarwal, Ipsita; Przeworski, Molly
    • Proceedings of the National Academy of Sciences, Vol. 116, Issue 36
    • DOI: 10.1073/pnas.1900714116

    Mutations beget more mutations – The baseline mutation rate and runaway accumulation
    posted_content, July 2019

    • Ruan, Yongsen; Chen, Bingjie; Chen, Qingjian
    • Molecular Biology and Evolution
    • DOI: 10.1101/690099

    Mutations Beget More Mutations—Rapid Evolution of Mutation Rate in Response to the Risk of Runaway Accumulation
    journal, December 2019

    • Ruan, Yongsen; Wang, Haiyu; Chen, Bingjie
    • Molecular Biology and Evolution, Vol. 37, Issue 4
    • DOI: 10.1093/molbev/msz283

    Somatic mutagenesis in satellite cells associates with human skeletal muscle aging
    journal, February 2018

    Embryonal precursors of Wilms tumor
    journal, December 2019

    APOBEC mutation drives early-onset squamous cell carcinomas in recessive dystrophic epidermolysis bullosa
    journal, August 2018

    • Cho, Raymond J.; Alexandrov, Ludmil B.; den Breems, Nicoline Y.
    • Science Translational Medicine, Vol. 10, Issue 455
    • DOI: 10.1126/scitranslmed.aas9668

    The patterns of birthmarks suggest a novel population of melanocyte precursors arising around the time of gastrulation
    journal, October 2017

    • Kinsler, Veronica A.; Larue, Lionel
    • Pigment Cell & Melanoma Research, Vol. 31, Issue 1
    • DOI: 10.1111/pcmr.12645

    Concordance for clonal hematopoiesis is limited in elderly twins
    journal, January 2020

    Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis
    journal, December 2017

    Conbase: a software for unsupervised discovery of clonal somatic mutations in single cells through read phasing
    journal, April 2019

    Detection and genomic characterization of a mammary-like adenocarcinoma
    journal, September 2017

    • Grewal, Jasleen K.; Eirew, Peter; Jones, Martin
    • Molecular Case Studies, Vol. 3, Issue 6
    • DOI: 10.1101/mcs.a002170

    Signatures of replication timing, recombination, and sex in the spectrum of rare variants on the human X chromosome and autosomes
    journal, August 2019

    • Agarwal, Ipsita; Przeworski, Molly
    • Proceedings of the National Academy of Sciences, Vol. 116, Issue 36
    • DOI: 10.1073/pnas.1900714116

    Immune Cell Dynamics Unfolded by Single-Cell Technologies
    journal, June 2018

    Somatic Mutations Reveal Lineage Relationships and Age-Related Mutagenesis in Human Hematopoiesis
    journal, November 2018

    Linked-read analysis identifies mutations in single-cell DNA-sequencing data
    journal, March 2019

    Frequency of mosaicism points towards mutation-prone early cleavage cell divisions in cattle
    posted_content, June 2017

    • Harland, Chad; Charlier, Carole; Karim, Latifa
    • BioRxiv
    • DOI: 10.1101/079863

    Identification of somatic mutations in monozygotic twins discordant for psychiatric disorders
    journal, April 2018

    The rate and spectrum of mosaic mutations during embryogenesis revealed by RNA sequencing of 49 tissues
    journal, May 2020

    A characterization of postzygotic mutations identified in monozygotic twins
    journal, July 2018

    • Ouwens, Klaasjan G.; Jansen, Rick; Tolhuis, Bas
    • Human Mutation, Vol. 39, Issue 10
    • DOI: 10.1002/humu.23586

    An analysis of intrinsic base substitution patterns in diverse species reveals connections to cancer and metabolism
    posted_content, March 2020

    • Chan, Kin; Doherty, Kassidy N.; Alasmar, Salma
    • Genetics
    • DOI: 10.1101/758540

    Paternal age in rhesus macaques is positively associated with germline mutation accumulation but not with measures of offspring sociability
    posted_content, November 2019

    • Wang, Richard J.; Thomas, Gregg W. C.; Raveendran, Muthuswamy
    • Genome Research
    • DOI: 10.1101/706705

    Population dynamics of normal human blood inferred from somatic mutations.
    text, January 2018

    • Lee-Six, Henry; Øbro, Nina Friesgaard; Shepherd, Mairi
    • Apollo - University of Cambridge Repository
    • DOI: 10.17863/cam.28016

    Age-related clonal hematopoiesis
    journal, February 2018

    The rate and spectrum of mosaic mutations during embryogenesis revealed by RNA sequencing of 49 tissues
    posted_content, October 2019

    • Muyas, Francesc; Zapata, Luis; Guigó, Roderic
    • Genome Medicine
    • DOI: 10.1101/687822

    Mapping human development at single-cell resolution.
    text, January 2018

    • Behjati, Sam; Lindsay, Susan; Teichmann, Sarah
    • Apollo - University of Cambridge Repository
    • DOI: 10.17863/cam.39791

    Somatic Genetic Aberrations in Benign Breast Disease and the Risk of Subsequent Breast Cancer
    journal, April 2019

    • Zeng, Zexian; Vo, Andy; Li, Xiaoyu
    • npj Breast Cancer
    • DOI: 10.1101/613505

    Systematic comparative analysis of single-nucleotide variant detection methods from single-cell RNA sequencing data
    journal, November 2019

    Paternal age in rhesus macaques is positively associated with germline mutation accumulation but not with measures of offspring sociability
    posted_content, November 2019

    • Wang, Richard J.; Thomas, Gregg W. C.; Raveendran, Muthuswamy
    • Genome Research
    • DOI: 10.1101/706705

    Tracing the origin of heterogeneity and symmetry breaking in the early mammalian embryo
    journal, May 2018

    Somatic mutations in the human brain: implications for psychiatric research
    journal, August 2018

    Single-cell Lineage Tracing by Integrating CRISPR-Cas9 Mutations with Transcriptomic Data
    posted_content, May 2019

    • Zafar, Hamim; Lin, Chieh; Bar-Joseph, Ziv
    • Nature Communications
    • DOI: 10.1101/630814

    Paternal age in rhesus macaques is positively associated with germline mutation accumulation but not with measures of offspring sociability
    journal, May 2020

    • Wang, Richard J.; Thomas, Gregg W. C.; Raveendran, Muthuswamy
    • Genome Research, Vol. 30, Issue 6
    • DOI: 10.1101/gr.255174.119

    Predicting Gonadal Germ Cell Cancer in People with Disorders of Sex Development; Insights from Developmental Biology
    journal, October 2019

    • Looijenga, Leendert H. J.; Kao, Chia-Sui; Idrees, Muhammad T.
    • International Journal of Molecular Sciences, Vol. 20, Issue 20
    • DOI: 10.3390/ijms20205017

    Recurrent de novo mutations in neurodevelopmental disorders: properties and clinical implications
    journal, November 2017

    Simultaneous lineage tracing and cell-type identification using CRISPR–Cas9-induced genetic scars
    journal, April 2018

    • Spanjaard, Bastiaan; Hu, Bo; Mitic, Nina
    • Nature Biotechnology, Vol. 36, Issue 5
    • DOI: 10.1038/nbt.4124

    Systematic comparative analysis of single-nucleotide variant detection methods from single-cell RNA sequencing data
    journal, November 2019

    Overlooked roles of DNA damage and maternal age in generating human germline mutations
    journal, April 2019

    • Gao, Ziyue; Moorjani, Priya; Sasani, Thomas A.
    • Proceedings of the National Academy of Sciences, Vol. 116, Issue 19
    • DOI: 10.1073/pnas.1901259116

    Replicative cellular age distributions in compartmentalized tissues
    journal, August 2018

    • Böttcher, Marvin A.; Dingli, David; Werner, Benjamin
    • Journal of The Royal Society Interface, Vol. 15, Issue 145
    • DOI: 10.1098/rsif.2018.0272

    Genomic mosaicism in paternal sperm and multiple parental tissues in a Dravet syndrome cohort
    journal, November 2017

    Multiple transmissions of de novo mutations in families
    journal, November 2018

    Somatic mutations in the human brain: implications for psychiatric research
    journal, August 2018

    Recurrent de novo mutations in neurodevelopmental disorders: properties and clinical implications
    journal, November 2017

    Predicting Gonadal Germ Cell Cancer in People with Disorders of Sex Development; Insights from Developmental Biology
    journal, October 2019

    • Looijenga, Leendert H. J.; Kao, Chia-Sui; Idrees, Muhammad T.
    • International Journal of Molecular Sciences, Vol. 20, Issue 20
    • DOI: 10.3390/ijms20205017

    Age-related clonal hematopoiesis: implications for hematopoietic stem cell transplantation
    journal, January 2018

    Delayed Laparoscopic Cholecystectomy in a Case of Acute Cholecystitis and Intestinal Malrotation Type I
    journal, February 2019

    • Arias, Ana; Ordieres, Carlos; Huergo, Adrian
    • Clinics and Practice, Vol. 9, Issue 1
    • DOI: 10.4081/cp.2019.1091

    Early divergence of mutational processes in human fetal tissues
    journal, May 2019

    • Kuijk, Ewart; Blokzijl, Francis; Jager, Myrthe
    • Science Advances, Vol. 5, Issue 5
    • DOI: 10.1126/sciadv.aaw1271

    Mutalisk: a web-based somatic MUTation AnaLyIS toolKit for genomic, transcriptional and epigenomic signatures
    journal, May 2018

    • Lee, Jongkeun; Lee, Andy Jinseok; Lee, June-Koo
    • Nucleic Acids Research, Vol. 46, Issue W1
    • DOI: 10.1093/nar/gky406

    Mosaic abnormalities of the skin: review and guidelines from the European Reference Network for rare skin diseases
    journal, July 2019

    • Kinsler, V. A.; Boccara, O.; Fraitag, S.
    • British Journal of Dermatology
    • DOI: 10.1111/bjd.17924

    Simultaneous lineage tracing and cell-type identification using CRISPR–Cas9-induced genetic scars
    journal, April 2018

    • Spanjaard, Bastiaan; Hu, Bo; Mitic, Nina
    • Nature Biotechnology, Vol. 36, Issue 5
    • DOI: 10.1038/nbt.4124

    Germline and somatic mutations in cortical malformations: Molecular defects in Argentinean patients with neuronal migration disorders
    journal, September 2017

    Population dynamics of normal human blood inferred from somatic mutations
    journal, September 2018

    Overlooked roles of DNA damage and maternal age in generating human germline mutations
    journal, April 2019

    • Gao, Ziyue; Moorjani, Priya; Sasani, Thomas A.
    • Proceedings of the National Academy of Sciences, Vol. 116, Issue 19
    • DOI: 10.1073/pnas.1901259116

    A probabilistic framework for cellular lineage reconstruction using single-cell 5-hydroxymethylcytosine sequencing
    posted_content, August 2019

    • Wangsanuwat, Chatarin; Aldeguer, Javier F.; Rivron, Nicolas C.
    • BioRxiv
    • DOI: 10.1101/739300

    Somatic mutation load and spectra: A record of DNA damage and repair in healthy human cells: Human Somatic Mutation Load and Spectra
    journal, August 2018

    • Saini, Natalie; Gordenin, Dmitry A.
    • Environmental and Molecular Mutagenesis, Vol. 59, Issue 8
    • DOI: 10.1002/em.22215

    Networks of enhancers and microRNAs drive variation in cell states
    posted_content, June 2019

    • Chakraborty, Meenakshi; Hu, Sofia; Del Giudice, Marco
    • BioRxiv06/12/2
    • DOI: 10.1101/668145

    Quantification of somatic mutation flow across individual cell division events by lineage sequencing
    journal, November 2018

    • Brody, Yehuda; Kimmerling, Robert J.; Maruvka, Yosef E.
    • Genome Research, Vol. 28, Issue 12
    • DOI: 10.1101/gr.238543.118

    Accurate detection of mosaic variants in sequencing data without matched controls
    journal, January 2020

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