Comparison of genotyping assays for detection of targeted CRISPR/Cas mutagenesis in highly polyploid sugarcane

Sugarcane (Saccharum spp.) is an important biofuel feedstock and a leading source of global table sugar. Saccharum hybrid cultivars are highly polyploid (2n = 100–130), containing large numbers of functionally redundant hom(e)ologs in their genomes. Genome editing with sequence-specific nucleases ho...

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Main Authors: Eleanor J. Brant, David May, Ayman Eid, Fredy Altpeter
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Genome Editing
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Online Access:https://www.frontiersin.org/articles/10.3389/fgeed.2024.1505844/full
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author Eleanor J. Brant
Eleanor J. Brant
David May
David May
Ayman Eid
Ayman Eid
Fredy Altpeter
Fredy Altpeter
author_facet Eleanor J. Brant
Eleanor J. Brant
David May
David May
Ayman Eid
Ayman Eid
Fredy Altpeter
Fredy Altpeter
author_sort Eleanor J. Brant
collection DOAJ
description Sugarcane (Saccharum spp.) is an important biofuel feedstock and a leading source of global table sugar. Saccharum hybrid cultivars are highly polyploid (2n = 100–130), containing large numbers of functionally redundant hom(e)ologs in their genomes. Genome editing with sequence-specific nucleases holds tremendous promise for sugarcane breeding. However, identification of plants with the desired level of co-editing within a pool of primary transformants can be difficult. While DNA sequencing provides direct evidence of targeted mutagenesis, it is cost-prohibitive as a primary screening method in sugarcane and most other methods of identifying mutant lines have not been optimized for use in highly polyploid species. In this study, non-sequencing methods of mutant screening, including capillary electrophoresis (CE), Cas9 RNP assay, and high-resolution melt analysis (HRMA), were compared to assess their potential for CRISPR/Cas9-mediated mutant screening in sugarcane. These assays were used to analyze sugarcane lines containing mutations at one or more of six sgRNA target sites. All three methods distinguished edited lines from wild type, with co-mutation frequencies ranging from 2% to 100%. Cas9 RNP assays were able to identify mutant sugarcane lines with as low as 3.2% co-mutation frequency, and samples could be scored based on undigested band intensity. CE was highlighted as the most comprehensive assay, delivering precise information on both mutagenesis frequency and indel size to a 1 bp resolution across all six targets. This represents an economical and comprehensive alternative to sequencing-based genotyping methods which could be applied in other polyploid species.
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spelling doaj-art-e5fdcb7fdfdd439ab4bcae33e0f148162025-08-20T02:34:20ZengFrontiers Media S.A.Frontiers in Genome Editing2673-34392024-12-01610.3389/fgeed.2024.15058441505844Comparison of genotyping assays for detection of targeted CRISPR/Cas mutagenesis in highly polyploid sugarcaneEleanor J. Brant0Eleanor J. Brant1David May2David May3Ayman Eid4Ayman Eid5Fredy Altpeter6Fredy Altpeter7Agronomy Department, Plant Molecular and Cellular Biology Program, Genetics Institute, University of Florida, IFAS-Institute of Food and Agricultural Science, Gainesville, FL, United StatesDOE Center for Advanced Bioenergy and Bioproducts Innovation, Gainesville, FL, United StatesAgronomy Department, Plant Molecular and Cellular Biology Program, Genetics Institute, University of Florida, IFAS-Institute of Food and Agricultural Science, Gainesville, FL, United StatesDOE Center for Advanced Bioenergy and Bioproducts Innovation, Gainesville, FL, United StatesAgronomy Department, Plant Molecular and Cellular Biology Program, Genetics Institute, University of Florida, IFAS-Institute of Food and Agricultural Science, Gainesville, FL, United StatesDOE Center for Advanced Bioenergy and Bioproducts Innovation, Gainesville, FL, United StatesAgronomy Department, Plant Molecular and Cellular Biology Program, Genetics Institute, University of Florida, IFAS-Institute of Food and Agricultural Science, Gainesville, FL, United StatesDOE Center for Advanced Bioenergy and Bioproducts Innovation, Gainesville, FL, United StatesSugarcane (Saccharum spp.) is an important biofuel feedstock and a leading source of global table sugar. Saccharum hybrid cultivars are highly polyploid (2n = 100–130), containing large numbers of functionally redundant hom(e)ologs in their genomes. Genome editing with sequence-specific nucleases holds tremendous promise for sugarcane breeding. However, identification of plants with the desired level of co-editing within a pool of primary transformants can be difficult. While DNA sequencing provides direct evidence of targeted mutagenesis, it is cost-prohibitive as a primary screening method in sugarcane and most other methods of identifying mutant lines have not been optimized for use in highly polyploid species. In this study, non-sequencing methods of mutant screening, including capillary electrophoresis (CE), Cas9 RNP assay, and high-resolution melt analysis (HRMA), were compared to assess their potential for CRISPR/Cas9-mediated mutant screening in sugarcane. These assays were used to analyze sugarcane lines containing mutations at one or more of six sgRNA target sites. All three methods distinguished edited lines from wild type, with co-mutation frequencies ranging from 2% to 100%. Cas9 RNP assays were able to identify mutant sugarcane lines with as low as 3.2% co-mutation frequency, and samples could be scored based on undigested band intensity. CE was highlighted as the most comprehensive assay, delivering precise information on both mutagenesis frequency and indel size to a 1 bp resolution across all six targets. This represents an economical and comprehensive alternative to sequencing-based genotyping methods which could be applied in other polyploid species.https://www.frontiersin.org/articles/10.3389/fgeed.2024.1505844/fullpolyploidgenotypingmutationsCRISPR/Cas9high resolution meltcapillary electrophoresis
spellingShingle Eleanor J. Brant
Eleanor J. Brant
David May
David May
Ayman Eid
Ayman Eid
Fredy Altpeter
Fredy Altpeter
Comparison of genotyping assays for detection of targeted CRISPR/Cas mutagenesis in highly polyploid sugarcane
Frontiers in Genome Editing
polyploid
genotyping
mutations
CRISPR/Cas9
high resolution melt
capillary electrophoresis
title Comparison of genotyping assays for detection of targeted CRISPR/Cas mutagenesis in highly polyploid sugarcane
title_full Comparison of genotyping assays for detection of targeted CRISPR/Cas mutagenesis in highly polyploid sugarcane
title_fullStr Comparison of genotyping assays for detection of targeted CRISPR/Cas mutagenesis in highly polyploid sugarcane
title_full_unstemmed Comparison of genotyping assays for detection of targeted CRISPR/Cas mutagenesis in highly polyploid sugarcane
title_short Comparison of genotyping assays for detection of targeted CRISPR/Cas mutagenesis in highly polyploid sugarcane
title_sort comparison of genotyping assays for detection of targeted crispr cas mutagenesis in highly polyploid sugarcane
topic polyploid
genotyping
mutations
CRISPR/Cas9
high resolution melt
capillary electrophoresis
url https://www.frontiersin.org/articles/10.3389/fgeed.2024.1505844/full
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