Rapid Genotyping of <i>FecB</i> Mutation in Sheep Using CRISPR-Cas12a Integrated with DNA Nanotree Biosensing Platform

The A-to-G mutation (<i>FecB</i>) in the <i>BMPR1B</i> gene is strongly linked to fertility in sheep, significantly increasing ovulation rates and litter sizes compared to wild-type populations. The rapid and reliable screening of the <i>FecB</i> gene is therefore...

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Main Authors: Dongxia Pan, Mukaddas Mijit, Hui Wang, Chaoqun Sun, Bantan Pingcuo, Zhixue Yu, Benhai Xiong, Xiangfang Tang
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/3/315
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author Dongxia Pan
Mukaddas Mijit
Hui Wang
Chaoqun Sun
Bantan Pingcuo
Zhixue Yu
Benhai Xiong
Xiangfang Tang
author_facet Dongxia Pan
Mukaddas Mijit
Hui Wang
Chaoqun Sun
Bantan Pingcuo
Zhixue Yu
Benhai Xiong
Xiangfang Tang
author_sort Dongxia Pan
collection DOAJ
description The A-to-G mutation (<i>FecB</i>) in the <i>BMPR1B</i> gene is strongly linked to fertility in sheep, significantly increasing ovulation rates and litter sizes compared to wild-type populations. The rapid and reliable screening of the <i>FecB</i> gene is therefore critical for advancing sheep breeding programs. This study aimed to develop a fast and accurate method for detecting the <i>FecB</i> mutation and genotyping the gene to enhance sheep reproduction and productivity. To achieve this, we integrated the CRISPR-Cas12a system with an optimized amplification refractory mutation system (ARMS). A similar DNA origami technique-based fluorescence reporter nanotree structure was synthesized using gold nanomagnetic beads as carriers to amplify the fluorescence signal further. The resulting biosensing platform, termed CRISPR-ARMS, demonstrated excellent sensitivity for detecting <i>FecB</i> mutations, with a detection limit as low as 0.02 pmol. Therefore, this innovative approach shows great promise for single-base mutation detection and represents a pioneering tool for high-yield genetic screening.
format Article
id doaj-art-cce7b1d9d57a4f5f96817dbf32fc8641
institution Kabale University
issn 2218-273X
language English
publishDate 2025-02-01
publisher MDPI AG
record_format Article
series Biomolecules
spelling doaj-art-cce7b1d9d57a4f5f96817dbf32fc86412025-08-20T03:43:26ZengMDPI AGBiomolecules2218-273X2025-02-0115331510.3390/biom15030315Rapid Genotyping of <i>FecB</i> Mutation in Sheep Using CRISPR-Cas12a Integrated with DNA Nanotree Biosensing PlatformDongxia Pan0Mukaddas Mijit1Hui Wang2Chaoqun Sun3Bantan Pingcuo4Zhixue Yu5Benhai Xiong6Xiangfang Tang7State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science of CAAS, Beijing 100193, ChinaState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science of CAAS, Beijing 100193, ChinaState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science of CAAS, Beijing 100193, ChinaState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science of CAAS, Beijing 100193, ChinaInstitute of Animal Husbandry and Veterinary, Tibet Autonomous Regional Academy of Agricultural Sciences, Lhasa 850004, ChinaState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science of CAAS, Beijing 100193, ChinaState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science of CAAS, Beijing 100193, ChinaState Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science of CAAS, Beijing 100193, ChinaThe A-to-G mutation (<i>FecB</i>) in the <i>BMPR1B</i> gene is strongly linked to fertility in sheep, significantly increasing ovulation rates and litter sizes compared to wild-type populations. The rapid and reliable screening of the <i>FecB</i> gene is therefore critical for advancing sheep breeding programs. This study aimed to develop a fast and accurate method for detecting the <i>FecB</i> mutation and genotyping the gene to enhance sheep reproduction and productivity. To achieve this, we integrated the CRISPR-Cas12a system with an optimized amplification refractory mutation system (ARMS). A similar DNA origami technique-based fluorescence reporter nanotree structure was synthesized using gold nanomagnetic beads as carriers to amplify the fluorescence signal further. The resulting biosensing platform, termed CRISPR-ARMS, demonstrated excellent sensitivity for detecting <i>FecB</i> mutations, with a detection limit as low as 0.02 pmol. Therefore, this innovative approach shows great promise for single-base mutation detection and represents a pioneering tool for high-yield genetic screening.https://www.mdpi.com/2218-273X/15/3/315CRISPR-Cas12aamplification retarded mutation system<i>FecB</i>Fe<sub>3</sub>O<sub>4</sub>@Au-Linker-Cy5-Nanotreerapid detection
spellingShingle Dongxia Pan
Mukaddas Mijit
Hui Wang
Chaoqun Sun
Bantan Pingcuo
Zhixue Yu
Benhai Xiong
Xiangfang Tang
Rapid Genotyping of <i>FecB</i> Mutation in Sheep Using CRISPR-Cas12a Integrated with DNA Nanotree Biosensing Platform
Biomolecules
CRISPR-Cas12a
amplification retarded mutation system
<i>FecB</i>
Fe<sub>3</sub>O<sub>4</sub>@Au-Linker-Cy5-Nanotree
rapid detection
title Rapid Genotyping of <i>FecB</i> Mutation in Sheep Using CRISPR-Cas12a Integrated with DNA Nanotree Biosensing Platform
title_full Rapid Genotyping of <i>FecB</i> Mutation in Sheep Using CRISPR-Cas12a Integrated with DNA Nanotree Biosensing Platform
title_fullStr Rapid Genotyping of <i>FecB</i> Mutation in Sheep Using CRISPR-Cas12a Integrated with DNA Nanotree Biosensing Platform
title_full_unstemmed Rapid Genotyping of <i>FecB</i> Mutation in Sheep Using CRISPR-Cas12a Integrated with DNA Nanotree Biosensing Platform
title_short Rapid Genotyping of <i>FecB</i> Mutation in Sheep Using CRISPR-Cas12a Integrated with DNA Nanotree Biosensing Platform
title_sort rapid genotyping of i fecb i mutation in sheep using crispr cas12a integrated with dna nanotree biosensing platform
topic CRISPR-Cas12a
amplification retarded mutation system
<i>FecB</i>
Fe<sub>3</sub>O<sub>4</sub>@Au-Linker-Cy5-Nanotree
rapid detection
url https://www.mdpi.com/2218-273X/15/3/315
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