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Identification of a Novel Functional Non-synonymous Single Nucleotide Polymorphism in Frizzled Class Receptor 6 Gene for Involvement in Depressive Symptoms
Although numerous susceptibility loci for depression have been identified in recent years, their biological function and molecular mechanism remain largely unknown. By using an exome-wide association study for depressive symptoms assessed by the Center for Epidemiological Studies Depression (CES-D)...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302575/ https://www.ncbi.nlm.nih.gov/pubmed/35875672 http://dx.doi.org/10.3389/fnmol.2022.882396 |
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author | Han, Haijun Xu, Mengxiang Wen, Li Chen, Jiali Liu, Qiang Wang, Ju Li, Ming D. Yang, Zhongli |
author_facet | Han, Haijun Xu, Mengxiang Wen, Li Chen, Jiali Liu, Qiang Wang, Ju Li, Ming D. Yang, Zhongli |
author_sort | Han, Haijun |
collection | PubMed |
description | Although numerous susceptibility loci for depression have been identified in recent years, their biological function and molecular mechanism remain largely unknown. By using an exome-wide association study for depressive symptoms assessed by the Center for Epidemiological Studies Depression (CES-D) score, we discovered a novel missense single nucleotide polymorphism (SNP), rs61753730 (Q152E), located in the fourth exon of the frizzled class receptor 6 gene (FZD6), which is a potential causal variant and is significantly associated with the CES-D score. Computer-based in silico analysis revealed that the protein configuration and stability, as well as the secondary structure of FZD6 differed greatly between the wild-type (WT) and Q152E mutant. We further found that rs61753730 significantly affected the luciferase activity and expression of FZD6 in an allele-specific way. Finally, we generated Fzd6-knockin (Fzd6-KI) mice with rs61753730 mutation using the CRISPR/Cas9 genome editing system and found that these mice presented greater immobility in the forced swimming test, less preference for sucrose in the sucrose preference test, as well as decreased center entries, center time, and distance traveled in the open filed test compared with WT mice after exposed to chronic social defeat stress. These results indicate the involvement of rs61753730 in depression. Taken together, our findings demonstrate that SNP rs61753730 is a novel functional variant and plays an important role in depressive symptoms. |
format | Online Article Text |
id | pubmed-9302575 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93025752022-07-22 Identification of a Novel Functional Non-synonymous Single Nucleotide Polymorphism in Frizzled Class Receptor 6 Gene for Involvement in Depressive Symptoms Han, Haijun Xu, Mengxiang Wen, Li Chen, Jiali Liu, Qiang Wang, Ju Li, Ming D. Yang, Zhongli Front Mol Neurosci Neuroscience Although numerous susceptibility loci for depression have been identified in recent years, their biological function and molecular mechanism remain largely unknown. By using an exome-wide association study for depressive symptoms assessed by the Center for Epidemiological Studies Depression (CES-D) score, we discovered a novel missense single nucleotide polymorphism (SNP), rs61753730 (Q152E), located in the fourth exon of the frizzled class receptor 6 gene (FZD6), which is a potential causal variant and is significantly associated with the CES-D score. Computer-based in silico analysis revealed that the protein configuration and stability, as well as the secondary structure of FZD6 differed greatly between the wild-type (WT) and Q152E mutant. We further found that rs61753730 significantly affected the luciferase activity and expression of FZD6 in an allele-specific way. Finally, we generated Fzd6-knockin (Fzd6-KI) mice with rs61753730 mutation using the CRISPR/Cas9 genome editing system and found that these mice presented greater immobility in the forced swimming test, less preference for sucrose in the sucrose preference test, as well as decreased center entries, center time, and distance traveled in the open filed test compared with WT mice after exposed to chronic social defeat stress. These results indicate the involvement of rs61753730 in depression. Taken together, our findings demonstrate that SNP rs61753730 is a novel functional variant and plays an important role in depressive symptoms. Frontiers Media S.A. 2022-07-07 /pmc/articles/PMC9302575/ /pubmed/35875672 http://dx.doi.org/10.3389/fnmol.2022.882396 Text en Copyright © 2022 Han, Xu, Wen, Chen, Liu, Wang, Li and Yang. 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 | Neuroscience Han, Haijun Xu, Mengxiang Wen, Li Chen, Jiali Liu, Qiang Wang, Ju Li, Ming D. Yang, Zhongli Identification of a Novel Functional Non-synonymous Single Nucleotide Polymorphism in Frizzled Class Receptor 6 Gene for Involvement in Depressive Symptoms |
title | Identification of a Novel Functional Non-synonymous Single Nucleotide Polymorphism in Frizzled Class Receptor 6 Gene for Involvement in Depressive Symptoms |
title_full | Identification of a Novel Functional Non-synonymous Single Nucleotide Polymorphism in Frizzled Class Receptor 6 Gene for Involvement in Depressive Symptoms |
title_fullStr | Identification of a Novel Functional Non-synonymous Single Nucleotide Polymorphism in Frizzled Class Receptor 6 Gene for Involvement in Depressive Symptoms |
title_full_unstemmed | Identification of a Novel Functional Non-synonymous Single Nucleotide Polymorphism in Frizzled Class Receptor 6 Gene for Involvement in Depressive Symptoms |
title_short | Identification of a Novel Functional Non-synonymous Single Nucleotide Polymorphism in Frizzled Class Receptor 6 Gene for Involvement in Depressive Symptoms |
title_sort | identification of a novel functional non-synonymous single nucleotide polymorphism in frizzled class receptor 6 gene for involvement in depressive symptoms |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302575/ https://www.ncbi.nlm.nih.gov/pubmed/35875672 http://dx.doi.org/10.3389/fnmol.2022.882396 |
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