Novel rare frameshift variation in aggressive periodontitis: Exomic and familial-screening analysis

Tiago Taiete; Marcio Z. Casati; Luciane Martins; Denise C. Andia; Luciana S. Mofatto; Ricardo D. Coletta; Mabelle F. Monteiro; Cássia F. Araújo; Mauro P. Santamaria; Francisco H. Nociti; Mônica G. Corrêa; Enilson A. Sallum; Renato C. Casarin

doi:10.1002/JPER.19-0182

Novel rare frameshift variation in aggressive periodontitis: Exomic and familial-screening analysis

Tiago Taiete, Marcio Z. Casati, Luciane Martins, Denise C. Andia, Luciana S. Mofatto, Ricardo D. Coletta, Mabelle F. Monteiro, Cássia F. Araújo, Mauro P. Santamaria, Francisco H. Nociti, Mônica G. Corrêa, Enilson A. Sallum, Renato C. Casarin

Oral Health Practice

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4 Scopus citations

Abstract

Background: Aggressive periodontitis (AgP), currently periodontitis grade C, presents early onset, rapid progression, and a poorly established genetic association. Thus, this study aimed to identify genetic variants associated with AgP via whole exome sequencing (WES) through a familial screening approach. Methods: WES was performed in two nuclear families, including a proband and a parent affected by AgP and an unaffected parent and sibling. Common variants among affected individuals, excluding those common to healthy people, from each family, composed the data set associated with AgP. In silico analysis evaluated the impact of each variant on protein structure and protein-protein interactions. Moreover, identified deleterious variants were validated in a populational analysis (n = 96). Results: The missense single nucleotide variations (SNVs) rs142548867 in EEF-SEC (c.668C>T), rs574301770 in ZNF136 (c.466C>G), and rs72821893 in KRT25 (c.800G>A) and the frameshift indels rs37146475 in GPRC6A (c.2323-2324insT) and c.1366_1372insGGAGCAG in ELN were identified in AgP and have a predicted functional impact on proteins. In silico analysis indicated that the indel in GPRC6A generates a loss of the C-terminal tail of the Gprca protein. Furthermore, this SNV was significantly associated with AgP in a population-based investigation. Conclusion: Novel frameshift variation in GPRC6A (c.2323-2324insT) was identified as a potential genetic alteration associated with AgP occurrence.

Original language	English
Pages (from-to)	263-273
Number of pages	11
Journal	Journal of Periodontology
Volume	91
Issue number	2
DOIs	https://doi.org/10.1002/JPER.19-0182
State	Published - 2020

Bibliographical note

Funding Information:
The authors would like to thank Dr. Luiz Lehmann Coutinho at the Department of Animal Science, University of São Paulo, Piracicaba, Brazil, for allowing the use of his laboratory for the exome sequencing. We also thank Dr. Fabio Haach Téo (Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, Brazil) for helping us with the Sanger sequencing. Tiago Taiete was supported by the National Council for Scientific and Technological Development (CNPq – Brazil – Grant #140967/2013-3). The authors declare there are no conflicts of interest in this study.

Publisher Copyright:
© John Wiley and Sons Inc. All rights reserved.

Keywords

genetic association studies
genetic markers
genetic variation
genotype
periodontal diseases

ASJC Scopus subject areas

Periodontics

Access to Document

10.1002/JPER.19-0182

Cite this

Taiete, T., Casati, M. Z., Martins, L., Andia, D. C., Mofatto, L. S., Coletta, R. D., Monteiro, M. F., Araújo, C. F., Santamaria, M. P., Nociti, F. H., Corrêa, M. G., Sallum, E. A., & Casarin, R. C. (2020). Novel rare frameshift variation in aggressive periodontitis: Exomic and familial-screening analysis. Journal of Periodontology, 91(2), 263-273. https://doi.org/10.1002/JPER.19-0182

@article{91db0d5b730d4d32a650bac9b6de47c3,

title = "Novel rare frameshift variation in aggressive periodontitis: Exomic and familial-screening analysis",

abstract = "Background: Aggressive periodontitis (AgP), currently periodontitis grade C, presents early onset, rapid progression, and a poorly established genetic association. Thus, this study aimed to identify genetic variants associated with AgP via whole exome sequencing (WES) through a familial screening approach. Methods: WES was performed in two nuclear families, including a proband and a parent affected by AgP and an unaffected parent and sibling. Common variants among affected individuals, excluding those common to healthy people, from each family, composed the data set associated with AgP. In silico analysis evaluated the impact of each variant on protein structure and protein-protein interactions. Moreover, identified deleterious variants were validated in a populational analysis (n = 96). Results: The missense single nucleotide variations (SNVs) rs142548867 in EEF-SEC (c.668C>T), rs574301770 in ZNF136 (c.466C>G), and rs72821893 in KRT25 (c.800G>A) and the frameshift indels rs37146475 in GPRC6A (c.2323-2324insT) and c.1366_1372insGGAGCAG in ELN were identified in AgP and have a predicted functional impact on proteins. In silico analysis indicated that the indel in GPRC6A generates a loss of the C-terminal tail of the Gprca protein. Furthermore, this SNV was significantly associated with AgP in a population-based investigation. Conclusion: Novel frameshift variation in GPRC6A (c.2323-2324insT) was identified as a potential genetic alteration associated with AgP occurrence.",

keywords = "genetic association studies, genetic markers, genetic variation, genotype, periodontal diseases",

author = "Tiago Taiete and Casati, {Marcio Z.} and Luciane Martins and Andia, {Denise C.} and Mofatto, {Luciana S.} and Coletta, {Ricardo D.} and Monteiro, {Mabelle F.} and Ara{\'u}jo, {C{\'a}ssia F.} and Santamaria, {Mauro P.} and Nociti, {Francisco H.} and Corr{\^e}a, {M{\^o}nica G.} and Sallum, {Enilson A.} and Casarin, {Renato C.}",

note = "Funding Information: The authors would like to thank Dr. Luiz Lehmann Coutinho at the Department of Animal Science, University of S{\~a}o Paulo, Piracicaba, Brazil, for allowing the use of his laboratory for the exome sequencing. We also thank Dr. Fabio Haach T{\'e}o (Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, Brazil) for helping us with the Sanger sequencing. Tiago Taiete was supported by the National Council for Scientific and Technological Development (CNPq – Brazil – Grant #140967/2013-3). The authors declare there are no conflicts of interest in this study. Publisher Copyright: {\textcopyright} John Wiley and Sons Inc. All rights reserved.",

year = "2020",

doi = "10.1002/JPER.19-0182",

language = "English",

volume = "91",

pages = "263--273",

number = "2",

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TY - JOUR

T1 - Novel rare frameshift variation in aggressive periodontitis

T2 - Exomic and familial-screening analysis

AU - Taiete, Tiago

AU - Casati, Marcio Z.

AU - Martins, Luciane

AU - Andia, Denise C.

AU - Mofatto, Luciana S.

AU - Coletta, Ricardo D.

AU - Monteiro, Mabelle F.

AU - Araújo, Cássia F.

AU - Santamaria, Mauro P.

AU - Nociti, Francisco H.

AU - Corrêa, Mônica G.

AU - Sallum, Enilson A.

AU - Casarin, Renato C.

N1 - Funding Information: The authors would like to thank Dr. Luiz Lehmann Coutinho at the Department of Animal Science, University of São Paulo, Piracicaba, Brazil, for allowing the use of his laboratory for the exome sequencing. We also thank Dr. Fabio Haach Téo (Department of Oral Diagnosis, School of Dentistry, University of Campinas, Piracicaba, Brazil) for helping us with the Sanger sequencing. Tiago Taiete was supported by the National Council for Scientific and Technological Development (CNPq – Brazil – Grant #140967/2013-3). The authors declare there are no conflicts of interest in this study. Publisher Copyright: © John Wiley and Sons Inc. All rights reserved.

PY - 2020

Y1 - 2020

N2 - Background: Aggressive periodontitis (AgP), currently periodontitis grade C, presents early onset, rapid progression, and a poorly established genetic association. Thus, this study aimed to identify genetic variants associated with AgP via whole exome sequencing (WES) through a familial screening approach. Methods: WES was performed in two nuclear families, including a proband and a parent affected by AgP and an unaffected parent and sibling. Common variants among affected individuals, excluding those common to healthy people, from each family, composed the data set associated with AgP. In silico analysis evaluated the impact of each variant on protein structure and protein-protein interactions. Moreover, identified deleterious variants were validated in a populational analysis (n = 96). Results: The missense single nucleotide variations (SNVs) rs142548867 in EEF-SEC (c.668C>T), rs574301770 in ZNF136 (c.466C>G), and rs72821893 in KRT25 (c.800G>A) and the frameshift indels rs37146475 in GPRC6A (c.2323-2324insT) and c.1366_1372insGGAGCAG in ELN were identified in AgP and have a predicted functional impact on proteins. In silico analysis indicated that the indel in GPRC6A generates a loss of the C-terminal tail of the Gprca protein. Furthermore, this SNV was significantly associated with AgP in a population-based investigation. Conclusion: Novel frameshift variation in GPRC6A (c.2323-2324insT) was identified as a potential genetic alteration associated with AgP occurrence.

AB - Background: Aggressive periodontitis (AgP), currently periodontitis grade C, presents early onset, rapid progression, and a poorly established genetic association. Thus, this study aimed to identify genetic variants associated with AgP via whole exome sequencing (WES) through a familial screening approach. Methods: WES was performed in two nuclear families, including a proband and a parent affected by AgP and an unaffected parent and sibling. Common variants among affected individuals, excluding those common to healthy people, from each family, composed the data set associated with AgP. In silico analysis evaluated the impact of each variant on protein structure and protein-protein interactions. Moreover, identified deleterious variants were validated in a populational analysis (n = 96). Results: The missense single nucleotide variations (SNVs) rs142548867 in EEF-SEC (c.668C>T), rs574301770 in ZNF136 (c.466C>G), and rs72821893 in KRT25 (c.800G>A) and the frameshift indels rs37146475 in GPRC6A (c.2323-2324insT) and c.1366_1372insGGAGCAG in ELN were identified in AgP and have a predicted functional impact on proteins. In silico analysis indicated that the indel in GPRC6A generates a loss of the C-terminal tail of the Gprca protein. Furthermore, this SNV was significantly associated with AgP in a population-based investigation. Conclusion: Novel frameshift variation in GPRC6A (c.2323-2324insT) was identified as a potential genetic alteration associated with AgP occurrence.

KW - genetic association studies

KW - genetic markers

KW - genetic variation

KW - genotype

KW - periodontal diseases

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M3 - Article

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AN - SCOPUS:85079563918

SN - 0022-3492

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JO - Journal of Periodontology

JF - Journal of Periodontology

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ER -

Novel rare frameshift variation in aggressive periodontitis: Exomic and familial-screening analysis

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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