Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken
Runting and stunting syndrome (RSS), which is characterized by low body weight, generally occurs early in life and leads to considerable economic losses in the commercial broiler industry. Our previous study has suggested that RSS is associated with mitochondria dysfunction in sex-linked dwarf (SLD)...
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00581/full |
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| author | Bowen Hu Bowen Hu Minmin Yang Minmin Yang Zhiying Liao Zhiying Liao Haohui Wei Haohui Wei Changbin Zhao Changbin Zhao Dajian Li Dajian Li Shuang Hu Shuang Hu Xinsheng Jiang Meiqing Shi Qingbin Luo Qingbin Luo Dexiang Zhang Dexiang Zhang Qinghua Nie Qinghua Nie Xiquan Zhang Xiquan Zhang Hongmei Li Hongmei Li |
| author_facet | Bowen Hu Bowen Hu Minmin Yang Minmin Yang Zhiying Liao Zhiying Liao Haohui Wei Haohui Wei Changbin Zhao Changbin Zhao Dajian Li Dajian Li Shuang Hu Shuang Hu Xinsheng Jiang Meiqing Shi Qingbin Luo Qingbin Luo Dexiang Zhang Dexiang Zhang Qinghua Nie Qinghua Nie Xiquan Zhang Xiquan Zhang Hongmei Li Hongmei Li |
| author_sort | Bowen Hu |
| collection | DOAJ |
| description | Runting and stunting syndrome (RSS), which is characterized by low body weight, generally occurs early in life and leads to considerable economic losses in the commercial broiler industry. Our previous study has suggested that RSS is associated with mitochondria dysfunction in sex-linked dwarf (SLD) chickens. However, the molecular mechanism of RSS remains unknown. Based on the molecular diagnostics of mitochondrial diseases, we identified a recessive mutation c. 409G > A (p. Ala137Thr) of Twinkle mitochondrial DNA helicase (TWNK) gene and mitochondrial DNA (mtDNA) depletion in RSS chickens’ livers from strain N301. Bioinformatics investigations supported the pathogenicity of the TWNK mutation that is located on the extended peptide linker of Twinkle primase domain and might further lead to mtDNA depletion in chicken. Furthermore, overexpression of wild-type TWNK increases mtDNA copy number, whereas overexpression of TWNK A137T causes mtDNA depletion in vitro. Additionally, the TWNK c. 409G > A mutation showed significant associations with body weight, daily gain, pectoralis weight, crureus weight, and abdominal fat weight. Taken together, we corroborated that the recessive TWNK c. 409G > A (p. Ala137Thr) mutation is associated with RSS characterized by mtDNA depletion in SLD chicken. |
| first_indexed | 2024-12-20T12:38:07Z |
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| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-20T12:38:07Z |
| publishDate | 2020-07-01 |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-2f407f2476c54ff0aaf075d0112a84a12022-12-21T19:40:33ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-07-01810.3389/fcell.2020.00581535024Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf ChickenBowen Hu0Bowen Hu1Minmin Yang2Minmin Yang3Zhiying Liao4Zhiying Liao5Haohui Wei6Haohui Wei7Changbin Zhao8Changbin Zhao9Dajian Li10Dajian Li11Shuang Hu12Shuang Hu13Xinsheng Jiang14Meiqing Shi15Qingbin Luo16Qingbin Luo17Dexiang Zhang18Dexiang Zhang19Qinghua Nie20Qinghua Nie21Xiquan Zhang22Xiquan Zhang23Hongmei Li24Hongmei Li25Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of AgroAnimal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of AgroAnimal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of AgroAnimal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of AgroAnimal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of AgroAnimal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of AgroAnimal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of AgroAnimal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, ChinaGuangdong WenShi Group Co., Ltd., Guangdong, ChinaDivision of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD, United StatesDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of AgroAnimal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of AgroAnimal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of AgroAnimal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of AgroAnimal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, ChinaDepartment of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Lab of AgroAnimal Genomics and Molecular Breeding and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou, ChinaRunting and stunting syndrome (RSS), which is characterized by low body weight, generally occurs early in life and leads to considerable economic losses in the commercial broiler industry. Our previous study has suggested that RSS is associated with mitochondria dysfunction in sex-linked dwarf (SLD) chickens. However, the molecular mechanism of RSS remains unknown. Based on the molecular diagnostics of mitochondrial diseases, we identified a recessive mutation c. 409G > A (p. Ala137Thr) of Twinkle mitochondrial DNA helicase (TWNK) gene and mitochondrial DNA (mtDNA) depletion in RSS chickens’ livers from strain N301. Bioinformatics investigations supported the pathogenicity of the TWNK mutation that is located on the extended peptide linker of Twinkle primase domain and might further lead to mtDNA depletion in chicken. Furthermore, overexpression of wild-type TWNK increases mtDNA copy number, whereas overexpression of TWNK A137T causes mtDNA depletion in vitro. Additionally, the TWNK c. 409G > A mutation showed significant associations with body weight, daily gain, pectoralis weight, crureus weight, and abdominal fat weight. Taken together, we corroborated that the recessive TWNK c. 409G > A (p. Ala137Thr) mutation is associated with RSS characterized by mtDNA depletion in SLD chicken.https://www.frontiersin.org/article/10.3389/fcell.2020.00581/fullrunting and stunting syndromemitochondrial DNA depletionTWNKsex-linked dwarf chickenliver |
| spellingShingle | Bowen Hu Bowen Hu Minmin Yang Minmin Yang Zhiying Liao Zhiying Liao Haohui Wei Haohui Wei Changbin Zhao Changbin Zhao Dajian Li Dajian Li Shuang Hu Shuang Hu Xinsheng Jiang Meiqing Shi Qingbin Luo Qingbin Luo Dexiang Zhang Dexiang Zhang Qinghua Nie Qinghua Nie Xiquan Zhang Xiquan Zhang Hongmei Li Hongmei Li Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken Frontiers in Cell and Developmental Biology runting and stunting syndrome mitochondrial DNA depletion TWNK sex-linked dwarf chicken liver |
| title | Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken |
| title_full | Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken |
| title_fullStr | Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken |
| title_full_unstemmed | Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken |
| title_short | Mutation of TWNK Gene Is One of the Reasons of Runting and Stunting Syndrome Characterized by mtDNA Depletion in Sex-Linked Dwarf Chicken |
| title_sort | mutation of twnk gene is one of the reasons of runting and stunting syndrome characterized by mtdna depletion in sex linked dwarf chicken |
| topic | runting and stunting syndrome mitochondrial DNA depletion TWNK sex-linked dwarf chicken liver |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00581/full |
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