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Target-Sequencing of Female Infertility Pathogenic Gene Panel and a Novel TUBB8 Loss-of-Function Mutation

Genetic screening is an important approach for etiology determination and helps to optimize administration protocols in reproductive centers. After the first pathogenic gene of female infertility was reported in 2016, more and more new pathogenic genes were discovered, and we sought to develop an ef...

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Autores principales: Yuan, Hongxia, Chen, Jianhua, Li, Na, Miao, Hui, Chen, Yao, Lyu, Shuyan, Qiao, Yu, Yang, Guangping, Luo, Hui, Chen, Liangliang, Mao, Fei, Huang, Lingli, He, Yanni, Hu, Saifei, Miao, Congxiu, Qian, Yun, Feng, Ruizhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127544/
https://www.ncbi.nlm.nih.gov/pubmed/35620457
http://dx.doi.org/10.3389/fgene.2022.865103
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author Yuan, Hongxia
Chen, Jianhua
Li, Na
Miao, Hui
Chen, Yao
Lyu, Shuyan
Qiao, Yu
Yang, Guangping
Luo, Hui
Chen, Liangliang
Mao, Fei
Huang, Lingli
He, Yanni
Hu, Saifei
Miao, Congxiu
Qian, Yun
Feng, Ruizhi
author_facet Yuan, Hongxia
Chen, Jianhua
Li, Na
Miao, Hui
Chen, Yao
Lyu, Shuyan
Qiao, Yu
Yang, Guangping
Luo, Hui
Chen, Liangliang
Mao, Fei
Huang, Lingli
He, Yanni
Hu, Saifei
Miao, Congxiu
Qian, Yun
Feng, Ruizhi
author_sort Yuan, Hongxia
collection PubMed
description Genetic screening is an important approach for etiology determination and helps to optimize administration protocols in reproductive centers. After the first pathogenic gene of female infertility was reported in 2016, more and more new pathogenic genes were discovered, and we sought to develop an efficient and cost-effective method for genetic screening in patients. In this study, we designed a target-sequencing panel with 22 female infertility-related genes, namely, TUBB8, PATL2, WEE2, and PANX1 and sequenced 68 primary infertility (PI) and recurrent pregnancy loss (RPL) patients. We sequenced 68 samples reaching an average depth of 1559× and detected 3,134 variants. Among them, 62.2% were synonymous single-nucleotide variants (SNVs) and 36.3% were non-synonymous SNVs. The remaining 1.5% are indels (insertions and deletions) and stop-gains. DNAH11 and TUBB8 are the two genes that mutated most frequently. We also found a novel TUBB8 variant (c.898_900del; p.300_300del), proved its loss-of-function mechanism, and profiled the interactome of the wild-type (WT) and mutant TUBB8 proteins. Overall, this target-sequencing method provides an efficient and cost-effective approach for screening in IVF clinics and will support researchers for the discovery of new pathogenic variants.
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spelling pubmed-91275442022-05-25 Target-Sequencing of Female Infertility Pathogenic Gene Panel and a Novel TUBB8 Loss-of-Function Mutation Yuan, Hongxia Chen, Jianhua Li, Na Miao, Hui Chen, Yao Lyu, Shuyan Qiao, Yu Yang, Guangping Luo, Hui Chen, Liangliang Mao, Fei Huang, Lingli He, Yanni Hu, Saifei Miao, Congxiu Qian, Yun Feng, Ruizhi Front Genet Genetics Genetic screening is an important approach for etiology determination and helps to optimize administration protocols in reproductive centers. After the first pathogenic gene of female infertility was reported in 2016, more and more new pathogenic genes were discovered, and we sought to develop an efficient and cost-effective method for genetic screening in patients. In this study, we designed a target-sequencing panel with 22 female infertility-related genes, namely, TUBB8, PATL2, WEE2, and PANX1 and sequenced 68 primary infertility (PI) and recurrent pregnancy loss (RPL) patients. We sequenced 68 samples reaching an average depth of 1559× and detected 3,134 variants. Among them, 62.2% were synonymous single-nucleotide variants (SNVs) and 36.3% were non-synonymous SNVs. The remaining 1.5% are indels (insertions and deletions) and stop-gains. DNAH11 and TUBB8 are the two genes that mutated most frequently. We also found a novel TUBB8 variant (c.898_900del; p.300_300del), proved its loss-of-function mechanism, and profiled the interactome of the wild-type (WT) and mutant TUBB8 proteins. Overall, this target-sequencing method provides an efficient and cost-effective approach for screening in IVF clinics and will support researchers for the discovery of new pathogenic variants. Frontiers Media S.A. 2022-05-10 /pmc/articles/PMC9127544/ /pubmed/35620457 http://dx.doi.org/10.3389/fgene.2022.865103 Text en Copyright © 2022 Yuan, Chen, Li, Miao, Chen, Lyu, Qiao, Yang, Luo, Chen, Mao, Huang, He, Hu, Miao, Qian and Feng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Yuan, Hongxia
Chen, Jianhua
Li, Na
Miao, Hui
Chen, Yao
Lyu, Shuyan
Qiao, Yu
Yang, Guangping
Luo, Hui
Chen, Liangliang
Mao, Fei
Huang, Lingli
He, Yanni
Hu, Saifei
Miao, Congxiu
Qian, Yun
Feng, Ruizhi
Target-Sequencing of Female Infertility Pathogenic Gene Panel and a Novel TUBB8 Loss-of-Function Mutation
title Target-Sequencing of Female Infertility Pathogenic Gene Panel and a Novel TUBB8 Loss-of-Function Mutation
title_full Target-Sequencing of Female Infertility Pathogenic Gene Panel and a Novel TUBB8 Loss-of-Function Mutation
title_fullStr Target-Sequencing of Female Infertility Pathogenic Gene Panel and a Novel TUBB8 Loss-of-Function Mutation
title_full_unstemmed Target-Sequencing of Female Infertility Pathogenic Gene Panel and a Novel TUBB8 Loss-of-Function Mutation
title_short Target-Sequencing of Female Infertility Pathogenic Gene Panel and a Novel TUBB8 Loss-of-Function Mutation
title_sort target-sequencing of female infertility pathogenic gene panel and a novel tubb8 loss-of-function mutation
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127544/
https://www.ncbi.nlm.nih.gov/pubmed/35620457
http://dx.doi.org/10.3389/fgene.2022.865103
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