The Human Gene Damage Index as a Gene-level Approach to Prioritizing Exome Variants
ABSTRACT: The protein-coding exome of a patient with a monogenic disease contains about 20,000 variants, only one or two of which are disease causing. We found that 58% of rare variants in the protein-coding exome of the general population are located in only 2% of the genes. Prompted by this observ...
- Autores:
-
Itan, Yuval
Shang, Lei
Bertrand, Boisson
Patin, Etienne
Bolze, Alexandre
Moncada Vélez, Marcela
Scott, Eric
Ciancanelli, Michael
Lafaille, Fabien
Markle, Janet
Martinez Barricarte, Ruben
Jill de Jong, Sarah
Fei Kong, Xiao
Nitschke, Patrick
Belkadi, Aziz
Bustamante, Jacinta
Puel, Anne
Boisson-Dupuis, Stéphanie
Stenson, Peter D.
Gleeson, Joseph G.
Cooper, David N.
Quintana Murci, Lluis
Claverie, Jean Michel
Zhang, Shen Ying
Abel, Laurent
Casanova, Jean-Laurent
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2015
- Institución:
- Universidad de Antioquia
- Repositorio:
- Repositorio UdeA
- Idioma:
- eng
- OAI Identifier:
- oai:bibliotecadigital.udea.edu.co:10495/34974
- Acceso en línea:
- https://hdl.handle.net/10495/34974
- Palabra clave:
- Exome
Exoma
Mutation
Mutación
DNA Damage
Daño del ADN
- Rights
- openAccess
- License
- https://creativecommons.org/licenses/by-nc-nd/4.0/
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| dc.title.spa.fl_str_mv |
The Human Gene Damage Index as a Gene-level Approach to Prioritizing Exome Variants |
| title |
The Human Gene Damage Index as a Gene-level Approach to Prioritizing Exome Variants |
| spellingShingle |
The Human Gene Damage Index as a Gene-level Approach to Prioritizing Exome Variants Exome Exoma Mutation Mutación DNA Damage Daño del ADN |
| title_short |
The Human Gene Damage Index as a Gene-level Approach to Prioritizing Exome Variants |
| title_full |
The Human Gene Damage Index as a Gene-level Approach to Prioritizing Exome Variants |
| title_fullStr |
The Human Gene Damage Index as a Gene-level Approach to Prioritizing Exome Variants |
| title_full_unstemmed |
The Human Gene Damage Index as a Gene-level Approach to Prioritizing Exome Variants |
| title_sort |
The Human Gene Damage Index as a Gene-level Approach to Prioritizing Exome Variants |
| dc.creator.fl_str_mv |
Itan, Yuval Shang, Lei Bertrand, Boisson Patin, Etienne Bolze, Alexandre Moncada Vélez, Marcela Scott, Eric Ciancanelli, Michael Lafaille, Fabien Markle, Janet Martinez Barricarte, Ruben Jill de Jong, Sarah Fei Kong, Xiao Nitschke, Patrick Belkadi, Aziz Bustamante, Jacinta Puel, Anne Boisson-Dupuis, Stéphanie Stenson, Peter D. Gleeson, Joseph G. Cooper, David N. Quintana Murci, Lluis Claverie, Jean Michel Zhang, Shen Ying Abel, Laurent Casanova, Jean-Laurent |
| dc.contributor.author.none.fl_str_mv |
Itan, Yuval Shang, Lei Bertrand, Boisson Patin, Etienne Bolze, Alexandre Moncada Vélez, Marcela Scott, Eric Ciancanelli, Michael Lafaille, Fabien Markle, Janet Martinez Barricarte, Ruben Jill de Jong, Sarah Fei Kong, Xiao Nitschke, Patrick Belkadi, Aziz Bustamante, Jacinta Puel, Anne Boisson-Dupuis, Stéphanie Stenson, Peter D. Gleeson, Joseph G. Cooper, David N. Quintana Murci, Lluis Claverie, Jean Michel Zhang, Shen Ying Abel, Laurent Casanova, Jean-Laurent |
| dc.contributor.researchgroup.spa.fl_str_mv |
Inmunodeficiencias Primarias |
| dc.subject.decs.none.fl_str_mv |
Exome Exoma Mutation Mutación DNA Damage Daño del ADN |
| topic |
Exome Exoma Mutation Mutación DNA Damage Daño del ADN |
| description |
ABSTRACT: The protein-coding exome of a patient with a monogenic disease contains about 20,000 variants, only one or two of which are disease causing. We found that 58% of rare variants in the protein-coding exome of the general population are located in only 2% of the genes. Prompted by this observation, we aimed to develop a gene-level approach for predicting whether a given human protein-coding gene is likely to harbor disease-causing mutations. To this end, we derived the gene damage index (GDI): a genome-wide, gene-level metric of the mutational damage that has accumulated in the general population. We found that the GDI was correlated with selective evolutionary pressure, protein complexity, coding sequence length, and the number of paralogs. We compared GDI with the leading gene-level approaches, genic intolerance, and de novo excess, and demonstrated that GDI performed best for the detection of false positives (i.e., removing exome variants in genes irrelevant to disease), whereas genic intolerance and de novo excess performed better for the detection of true positives (i.e., assessing de novo mutations in genes likely to be disease causing). |
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2015 |
| dc.date.issued.none.fl_str_mv |
2015 |
| dc.date.accessioned.none.fl_str_mv |
2023-05-11T16:17:09Z |
| dc.date.available.none.fl_str_mv |
2023-05-11T16:17:09Z |
| dc.type.spa.fl_str_mv |
Artículo de investigación |
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http://purl.org/coar/resource_type/c_2df8fbb1 |
| dc.type.redcol.spa.fl_str_mv |
https://purl.org/redcol/resource_type/ART |
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http://purl.org/coar/version/c_970fb48d4fbd8a85 |
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info:eu-repo/semantics/article |
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info:eu-repo/semantics/publishedVersion |
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http://purl.org/coar/resource_type/c_2df8fbb1 |
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Itan Y, Shang L, Boisson B, Patin E, Bolze A, Moncada-Vélez M, Scott E, Ciancanelli MJ, Lafaille FG, Markle JG, Martinez-Barricarte R, de Jong SJ, Kong XF, Nitschke P, Belkadi A, Bustamante J, Puel A, Boisson-Dupuis S, Stenson PD, Gleeson JG, Cooper DN, Quintana-Murci L, Claverie JM, Zhang SY, Abel L, Casanova JL. The human gene damage index as a gene-level approach to prioritizing exome variants. Proc Natl Acad Sci U S A. 2015 Nov 3;112(44):13615-20. doi: 10.1073/pnas.1518646112 |
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0027-8424 |
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https://hdl.handle.net/10495/34974 |
| dc.identifier.doi.none.fl_str_mv |
10.1073/pnas.1518646112 |
| dc.identifier.eissn.none.fl_str_mv |
091-6490 |
| identifier_str_mv |
Itan Y, Shang L, Boisson B, Patin E, Bolze A, Moncada-Vélez M, Scott E, Ciancanelli MJ, Lafaille FG, Markle JG, Martinez-Barricarte R, de Jong SJ, Kong XF, Nitschke P, Belkadi A, Bustamante J, Puel A, Boisson-Dupuis S, Stenson PD, Gleeson JG, Cooper DN, Quintana-Murci L, Claverie JM, Zhang SY, Abel L, Casanova JL. The human gene damage index as a gene-level approach to prioritizing exome variants. Proc Natl Acad Sci U S A. 2015 Nov 3;112(44):13615-20. doi: 10.1073/pnas.1518646112 0027-8424 10.1073/pnas.1518646112 091-6490 |
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https://hdl.handle.net/10495/34974 |
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eng |
| language |
eng |
| dc.relation.ispartofjournalabbrev.spa.fl_str_mv |
Proc. Natl. Acad. Sci. U. S. A. |
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13625 |
| dc.relation.citationissue.spa.fl_str_mv |
44 |
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13615 |
| dc.relation.citationvolume.spa.fl_str_mv |
112 |
| dc.relation.ispartofjournal.spa.fl_str_mv |
Proceedings of the National Academy of Sciences of the United States of America |
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https://creativecommons.org/licenses/by-nc-nd/4.0/ |
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http://creativecommons.org/licenses/by-nc-nd/2.5/co/ |
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info:eu-repo/semantics/openAccess |
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National Academy of Sciences |
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Washington, Estados Unidos |
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sin facultad - programa |
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Itan, YuvalShang, LeiBertrand, BoissonPatin, EtienneBolze, AlexandreMoncada Vélez, MarcelaScott, EricCiancanelli, MichaelLafaille, FabienMarkle, JanetMartinez Barricarte, RubenJill de Jong, SarahFei Kong, XiaoNitschke, PatrickBelkadi, AzizBustamante, JacintaPuel, AnneBoisson-Dupuis, StéphanieStenson, Peter D.Gleeson, Joseph G.Cooper, David N.Quintana Murci, LluisClaverie, Jean MichelZhang, Shen YingAbel, LaurentCasanova, Jean-LaurentInmunodeficiencias Primarias2023-05-11T16:17:09Z2023-05-11T16:17:09Z2015Itan Y, Shang L, Boisson B, Patin E, Bolze A, Moncada-Vélez M, Scott E, Ciancanelli MJ, Lafaille FG, Markle JG, Martinez-Barricarte R, de Jong SJ, Kong XF, Nitschke P, Belkadi A, Bustamante J, Puel A, Boisson-Dupuis S, Stenson PD, Gleeson JG, Cooper DN, Quintana-Murci L, Claverie JM, Zhang SY, Abel L, Casanova JL. The human gene damage index as a gene-level approach to prioritizing exome variants. Proc Natl Acad Sci U S A. 2015 Nov 3;112(44):13615-20. doi: 10.1073/pnas.15186461120027-8424https://hdl.handle.net/10495/3497410.1073/pnas.1518646112091-6490ABSTRACT: The protein-coding exome of a patient with a monogenic disease contains about 20,000 variants, only one or two of which are disease causing. We found that 58% of rare variants in the protein-coding exome of the general population are located in only 2% of the genes. Prompted by this observation, we aimed to develop a gene-level approach for predicting whether a given human protein-coding gene is likely to harbor disease-causing mutations. To this end, we derived the gene damage index (GDI): a genome-wide, gene-level metric of the mutational damage that has accumulated in the general population. We found that the GDI was correlated with selective evolutionary pressure, protein complexity, coding sequence length, and the number of paralogs. We compared GDI with the leading gene-level approaches, genic intolerance, and de novo excess, and demonstrated that GDI performed best for the detection of false positives (i.e., removing exome variants in genes irrelevant to disease), whereas genic intolerance and de novo excess performed better for the detection of true positives (i.e., assessing de novo mutations in genes likely to be disease causing).COL00124266application/pdfengNational Academy of SciencesWashington, Estados Unidossin facultad - programahttps://creativecommons.org/licenses/by-nc-nd/4.0/http://creativecommons.org/licenses/by-nc-nd/2.5/co/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2The Human Gene Damage Index as a Gene-level Approach to Prioritizing Exome VariantsArtículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionExomeExomaMutationMutaciónDNA DamageDaño del ADNProc. Natl. Acad. Sci. U. S. 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