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CRISPR: a versatile tool for both forward and reverse genetics research

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Abstract

Human genetics research employs the two opposing approaches of forward and reverse genetics. While forward genetics identifies and links a mutation to an observed disease etiology, reverse genetics induces mutations in model organisms to study their role in disease. In most cases, causality for mutations identified by forward genetics is confirmed by reverse genetics through the development of genetically engineered animal models and an assessment of whether the model can recapitulate the disease. While many technological advances have helped improve these approaches, some gaps still remain. CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated), which has emerged as a revolutionary genetic engineering tool, holds great promise for closing such gaps. By combining the benefits of forward and reverse genetics, it has dramatically expedited human genetics research. We provide a perspective on the power of CRISPR-based forward and reverse genetics tools in human genetics and discuss its applications using some disease examples.

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Acknowledgments

We thank Sidi Chen for his helpful comments on the manuscript. CBG’s lab is partially supported by National Institute of General Medical Sciences of the National Institutes of Health under Grant No. P20GM103471 and the Center for Humanized Mice from ORIP/DPCPSI/NIH/1R24OD018546-01. XZL’s lab is supported by R01 DC05575, R01 DC01246, and R01 DC012115 from the National Institutes of Health/National Institute on Deafness and Other Communication Disorders. SLPS is supported by the NSF Graduate Research Fellowship DGE1144152. Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation. We apologize to colleagues whose studies could not be cited because of space constraints.

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Authors and Affiliations

  1. Developmental Neuroscience, Munroe Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, USA

    Channabasavaiah B. Gurumurthy

  2. Mouse Genome Engineering Core Facility, Vice Chancellor for Research Office, University of Nebraska Medical Center, Omaha, NE, USA

    Channabasavaiah B. Gurumurthy & Rolen M. Quadros

  3. Otolaryngology Department, University of Miami Miller School of Medicine, Miami, FL, USA

    M’hamed Grati & Xue Zhong Liu

  4. Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, School of Medicine, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan

    Masato Ohtsuka

  5. The Institute of Medical Sciences, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan

    Masato Ohtsuka

  6. Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA

    Samantha L. P. Schilit

  7. Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Xue Zhong Liu

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  1. Channabasavaiah B. Gurumurthy
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  2. M’hamed Grati
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  3. Masato Ohtsuka
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  4. Samantha L. P. Schilit
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  5. Rolen M. Quadros
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Correspondence to Channabasavaiah B. Gurumurthy or M’hamed Grati.

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Gurumurthy, C.B., Grati, M., Ohtsuka, M. et al. CRISPR: a versatile tool for both forward and reverse genetics research. Hum Genet 135, 971–976 (2016). https://doi.org/10.1007/s00439-016-1704-4

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