Correction of Down syndrome and Edwards syndrome aneuploidies in human cell cultures

DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes
Tomokazu AmanoMinoru S H Ko

Abstract

Aneuploidy, an abnormal number of chromosomes, has previously been considered irremediable. Here, we report findings that euploid cells increased among cultured aneuploid cells after exposure to the protein ZSCAN4, encoded by a mammalian-specific gene that is ordinarily expressed in preimplantation embryos and occasionally in stem cells. For footprint-free delivery of ZSCAN4 to cells, we developed ZSCAN4 synthetic mRNAs and Sendai virus vectors that encode human ZSCAN4. Applying the ZSCAN4 biologics to established cultures of mouse embryonic stem cells, most of which had become aneuploid and polyploid, dramatically increased the number of euploid cells within a few days. We then tested the biologics on non-immortalized primary human fibroblast cells derived from four individuals with Down syndrome—the most frequent autosomal trisomy of chromosome 21. Within weeks after ZSCAN4 application to the cells in culture, fluorescent in situ hybridization with a chromosome 21-specific probe detected the emergence of up to 24% of cells with only two rather than three copies. High-resolution G-banded chromosomes further showed up to 40% of cells with a normal karyotype. These findings were confirmed by whole-exome sequencing. Similar resul...Continue Reading

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Citations

Nov 5, 2016·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Kathleen PlonaAnthony Wynshaw-Boris
Dec 27, 2019·American Journal on Intellectual and Developmental Disabilities·Kirsten A RigganMegan A Allyse
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Jul 30, 2021·Frontiers in Aging Neuroscience·Jose L MartinezAnita Bhattacharyya

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Datasets Mentioned

BETA
AG06872

Methods Mentioned

BETA
in vitro transcription
fluorescence microscopy
PCR
exome sequencing
transfection
fluorescence

Software Mentioned

BWA
GATK
Excel
Genome Analysis Tool Kit ( GATK
The
VarSifter
SAMtools
Genome Analysis Toolkit ( GATK )

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