Exome sequencing in the knockin mice generated using the CRISPR/Cas system

Nakajima, Kazuo; Kazuno, An‐a; Kelsoe, John R.; Nakanishi, Moe; Takumi, Toru; Kato, Takeshi

doi:10.1038/srep34703

Cited by 37 publications

(30 citation statements)

References 25 publications

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“…One of the few studies to look for off-target mutations at sites not predicted by online CRISPR design tools used exome sequencing of F1 knock-in mice generated using homology directed repair30. This study was small, examining DNA from only 4 mice, but one insertion and one deletion was found in one of the mice, and an insertion in a further mouse; two of these mutations would be predicted to be deleterious.…”

Section: Discussionmentioning

confidence: 99%

Biallelic mutations in the gene encoding eEF1A2 cause seizures and sudden death in F0 mice

Davies

Hope

McLachlan

et al. 2017

Sci Rep

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De novo heterozygous missense mutations in the gene encoding translation elongation factor eEF1A2 have recently been found to give rise to neurodevelopmental disorders. Children with mutations in this gene have developmental delay, epilepsy, intellectual disability and often autism; the most frequently occurring mutation is G70S. It has been known for many years that complete loss of eEF1A2 in mice causes motor neuron degeneration and early death; on the other hand heterozygous null mice are apparently normal. We have used CRISPR/Cas9 gene editing in the mouse to mutate the gene encoding eEF1A2, obtaining a high frequency of biallelic mutations. Whilst many of the resulting founder (F0) mice developed motor neuron degeneration, others displayed phenotypes consistent with a severe neurodevelopmental disorder, including sudden unexplained deaths and audiogenic seizures. The presence of G70S protein was not sufficient to protect mice from neurodegeneration in G70S/− mice, showing that the mutant protein is essentially non-functional.

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Section: Discussionmentioning

confidence: 99%

Biallelic mutations in the gene encoding eEF1A2 cause seizures and sudden death in F0 mice

Davies

Hope

McLachlan

et al. 2017

Sci Rep

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“…One notable study used single cell labeling of proteins via HDR within neuronal progenitors to allow for imaging of endogenous proteins [151]. HDR has also been successful in vivo for the creation of customized knock in mice [49,152–155]. …”

Section: Gain Of Function Strategiesmentioning

confidence: 99%

Functional interrogation of non-coding DNA through CRISPR genome editing

Canver

Bauer

Orkin

2017

Methods

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Methodologies to interrogate non-coding regions have lagged behind coding regions despite comprising the vast majority of the genome. However, the rapid evolution of clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing has provided a multitude of novel techniques for laboratory investigation including significant contributions to the toolbox for studying non-coding DNA. CRISPR-mediated loss-of-function strategies rely on direct disruption of the underlying sequence or repression of transcription without modifying the targeted DNA sequence. CRISPR-mediated gain-of-function approaches similarly benefit from methods to alter the targeted sequence through integration of customized sequence into the genome as well as methods to activate transcription. Here we review CRISPR-based loss- and gain-of-function techniques for the interrogation of non-coding DNA.

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“…Additionally, some studies have begun to perform whole exome sequencing (WES) in CRISPR-treated cells and organisms (55, 56). While these studies are the most accurate and comprehensive to-date, they still only detect approximately 1% of the genome, and it is known that non-coding regions also play crucial roles in the cell (57).…”

Section: Potential Limitations To Using the Crispr System In Patientsmentioning

confidence: 99%

CRISPR-Mediated Ophthalmic Genome Surgery

Cho

Abdulla

Sengillo

et al. 2017

Curr Ophthalmol Rep

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Purpose of review Clustered regularly interspaced short palindromic repeats (CRISPR) is a genome engineering system with great potential for clinical applications due to its versatility and programmability. This review highlights the development and use of CRISPR-mediated ophthalmic genome surgery in recent years. Recent findings Diverse CRISPR techniques are in development to target a wide array of ophthalmic conditions, including inherited and acquired conditions. Preclinical disease modeling and recent successes in gene editing suggest potential efficacy of CRISPR as a therapeutic for inherited conditions. In particular, the treatment of Leber congenital amaurosis with CRISPR-mediated genome surgery is expected to reach clinical trials in the near future. Summary Treatment options for inherited retinal dystrophies are currently limited. CRISPR-mediated genome surgery methods may be able to address this unmet need in the future.

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Exome sequencing in the knockin mice generated using the CRISPR/Cas system

Cited by 37 publications

References 25 publications

Biallelic mutations in the gene encoding eEF1A2 cause seizures and sudden death in F0 mice

Biallelic mutations in the gene encoding eEF1A2 cause seizures and sudden death in F0 mice

Functional interrogation of non-coding DNA through CRISPR genome editing

CRISPR-Mediated Ophthalmic Genome Surgery

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