Targeting chromosome trisomy for chromosome editing

Abstract A trisomy is a type of aneuploidy characterised by an additional chromosome. The additional chromosome theoretically accepts any kind of changes since it is not necessary for cellular proliferation. This advantage led us to apply two chromosome manipulation methods to autosomal trisomy in c...

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Autores principales: Takuya Abe, Yuya Suzuki, Teppei Ikeya, Kouji Hirota
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/0e11f84f775b4b3cbe945e698523f711
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spelling oai:doaj.org-article:0e11f84f775b4b3cbe945e698523f7112021-12-02T17:41:18ZTargeting chromosome trisomy for chromosome editing10.1038/s41598-021-97580-12045-2322https://doaj.org/article/0e11f84f775b4b3cbe945e698523f7112021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97580-1https://doaj.org/toc/2045-2322Abstract A trisomy is a type of aneuploidy characterised by an additional chromosome. The additional chromosome theoretically accepts any kind of changes since it is not necessary for cellular proliferation. This advantage led us to apply two chromosome manipulation methods to autosomal trisomy in chicken DT40 cells. We first corrected chromosome 2 trisomy to disomy by employing counter-selection markers. Upon construction of cells carrying markers targeted in one of the trisomic chromosome 2s, cells that have lost markers integrated in chromosome 2 were subsequently selected. The loss of one of the chromosome 2s had little impacts on the proliferative capacity, indicating unsubstantial role of the additional chromosome 2 in DT40 cells. We next tested large-scale truncations of chromosome 2 to make a mini-chromosome for the assessment of chromosome stability by introducing telomere repeat sequences to delete most of p-arm or q-arm of chromosome 2. The obtained cell lines had 0.7 Mb mini-chromosome, and approximately 0.2% of mini-chromosome was lost per cell division in wild-type background while the rate of chromosome loss was significantly increased by the depletion of DDX11, a cohesin regulatory protein. Collectively, our findings propose that trisomic chromosomes are good targets to make unique artificial chromosomes.Takuya AbeYuya SuzukiTeppei IkeyaKouji HirotaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Takuya Abe
Yuya Suzuki
Teppei Ikeya
Kouji Hirota
Targeting chromosome trisomy for chromosome editing
description Abstract A trisomy is a type of aneuploidy characterised by an additional chromosome. The additional chromosome theoretically accepts any kind of changes since it is not necessary for cellular proliferation. This advantage led us to apply two chromosome manipulation methods to autosomal trisomy in chicken DT40 cells. We first corrected chromosome 2 trisomy to disomy by employing counter-selection markers. Upon construction of cells carrying markers targeted in one of the trisomic chromosome 2s, cells that have lost markers integrated in chromosome 2 were subsequently selected. The loss of one of the chromosome 2s had little impacts on the proliferative capacity, indicating unsubstantial role of the additional chromosome 2 in DT40 cells. We next tested large-scale truncations of chromosome 2 to make a mini-chromosome for the assessment of chromosome stability by introducing telomere repeat sequences to delete most of p-arm or q-arm of chromosome 2. The obtained cell lines had 0.7 Mb mini-chromosome, and approximately 0.2% of mini-chromosome was lost per cell division in wild-type background while the rate of chromosome loss was significantly increased by the depletion of DDX11, a cohesin regulatory protein. Collectively, our findings propose that trisomic chromosomes are good targets to make unique artificial chromosomes.
format article
author Takuya Abe
Yuya Suzuki
Teppei Ikeya
Kouji Hirota
author_facet Takuya Abe
Yuya Suzuki
Teppei Ikeya
Kouji Hirota
author_sort Takuya Abe
title Targeting chromosome trisomy for chromosome editing
title_short Targeting chromosome trisomy for chromosome editing
title_full Targeting chromosome trisomy for chromosome editing
title_fullStr Targeting chromosome trisomy for chromosome editing
title_full_unstemmed Targeting chromosome trisomy for chromosome editing
title_sort targeting chromosome trisomy for chromosome editing
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/0e11f84f775b4b3cbe945e698523f711
work_keys_str_mv AT takuyaabe targetingchromosometrisomyforchromosomeediting
AT yuyasuzuki targetingchromosometrisomyforchromosomeediting
AT teppeiikeya targetingchromosometrisomyforchromosomeediting
AT koujihirota targetingchromosometrisomyforchromosomeediting
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