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Approaches and Methods for Variant Analysis in the Genome of a Single Cell

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Biomarkers of Human Aging

Part of the book series: Healthy Ageing and Longevity ((HAL,volume 10))

Abstract

Every cell in the human body has genomic variants that are either inherited or acquired during lifetime as a result of development, environmental exposure, and aging. Contrary to the former ones, the latter are present in a fraction of cells, which could be as small as a single cell, and are called mosaic variants. Therefore, studying single cells is the ultimate way of analyzing these variants. Analysis of a single cell genome is challenging due to low DNA amounts, and several strategies exist to amplify the DNA. The amplifications introduce errors and biases in the resulting material, which hinder the discovery of true variants. Furthermore, proper analytical considerations are important for both resolving introduced errors and comprehensive variant discovery. Thus, confident variant detection depends on combinations of the following four factors: (1) frequency and type of a mosaic variant; (2) strategy utilized for the discovery; (3) applied experimental and analytical method; and (4) funds and effort that can be invested into each experiment. As of now, none of the existing strategies and techniques are universally applicable to variants of all types, nor are they universally cost effective. Here, we will discuss strategies, experimental techniques, and analytical methods for discovery of a spectrum of mosaic variants from single cell analyses and approaches for validation of discovered variants.

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Acknowledgements

We thank Dr. Shobana Sekar for useful discussions during the course of writing and help in preparing the chapter.

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Authors and Affiliations

  1. Department of Health Sciences Research, Center for Individualized Medicine, Mayo Clinic, 55905, Rochester, MN, US

    Alexej Abyzov & Vivekananda Sarangi

  2. Department of Neuroscience, Child Study Center, Yale Kavli Institute for Neuroscience, Yale University School of Medicine, 06520, New Haven, CT, US

    Flora M. Vaccarino

  3. Department of Psychiatry and Behavioral Sciences and Department of Genetics, Stanford University School of Medicine, Stanford Center for Genomics and Personalized Medicine, 94304-1213, Palo Alto, CA, US

    Alexander E. Urban

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  1. Alexej Abyzov
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  2. Flora M. Vaccarino
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  3. Alexander E. Urban
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Correspondence to Alexej Abyzov .

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  1. Laboratory of Geroprotective and Radioprotective Technologies, Institute of Biology, Komi Science Center of RAS, Syktyvkar, Komi Republic, Russia

    Alexey Moskalev

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Abyzov, A., Vaccarino, F.M., Urban, A.E., Sarangi, V. (2019). Approaches and Methods for Variant Analysis in the Genome of a Single Cell. In: Moskalev, A. (eds) Biomarkers of Human Aging. Healthy Ageing and Longevity, vol 10. Springer, Cham. https://doi.org/10.1007/978-3-030-24970-0_14

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