Definition of mutations in polyautoimmunity

Angad Johar, Juan C. Sarmiento-Monroy, Adriana Rojas-Villarraga, Maria F. Silva-Lara, Hardip R. Patel, Ruben D. Mantilla, Jorge I. Velez, Klaus Martin Schulte, Claudio Mastronardi, Mauricio Arcos-Burgos, Juan Manuel Anaya

Resultado de la investigación: Contribución a RevistaArtículo

5 Citas (Scopus)

Resumen

© 2016 Elsevier LtdObjectives Familial autoimmunity and polyautoimmunity represent extreme phenotypes ideal for identifying major genomic variants contributing to autoimmunity. Whole exome sequencing (WES) and linkage analysis are well suited for this purpose due to its strong resolution upon familial segregation patterns of functional protein coding and splice variants. The primary objective of this study was to identify potentially autoimmune causative variants using WES data from extreme pedigrees segregating polyautoimmunity phenotypes. Methods DNA of 47 individuals across 10 extreme pedigrees, ascertained from probands affected with polyautoimmunity and familial autoimmunity, were selected for WES. Variant calls were obtained through Genome Analysis Toolkit. Filtration and prioritization framework to identify mutation(s) were applied, and later implemented for genetic linkage analysis. Sanger sequencing corroborated variants with significant linkage. Results Novel and mostly rare variants harbored in SRA1, MLL4, ABCB8, DHX34 and PLAUR showed significant linkage (LOD scores are >3.0). The strongest signal was in SRA1, with a LOD score of 5.48. Network analyses indicated that SRA1, PLAUR and ABCB8 contribute to regulation of apoptotic processes. Conclusions Novel and rare variants in genetic linkage with polyautoimmunity were identified throughout WES. Genes harboring these variants might be major players of autoimmunity.
Idioma originalEnglish (US)
Páginas (desde-hasta)65-72
Número de páginas8
PublicaciónJournal of Autoimmunity
DOI
EstadoPublished - ago 1 2016

Huella dactilar

Exome
Autoimmunity
Mutation
Genetic Linkage
Pedigree
Phenotype
Protein Isoforms
Genome
DNA
Genes

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Johar, A., Sarmiento-Monroy, J. C., Rojas-Villarraga, A., Silva-Lara, M. F., Patel, H. R., Mantilla, R. D., ... Anaya, J. M. (2016). Definition of mutations in polyautoimmunity. Journal of Autoimmunity, 65-72. https://doi.org/10.1016/j.jaut.2016.05.003
Johar, Angad ; Sarmiento-Monroy, Juan C. ; Rojas-Villarraga, Adriana ; Silva-Lara, Maria F. ; Patel, Hardip R. ; Mantilla, Ruben D. ; Velez, Jorge I. ; Schulte, Klaus Martin ; Mastronardi, Claudio ; Arcos-Burgos, Mauricio ; Anaya, Juan Manuel. / Definition of mutations in polyautoimmunity. En: Journal of Autoimmunity. 2016 ; pp. 65-72.
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title = "Definition of mutations in polyautoimmunity",
abstract = "{\circledC} 2016 Elsevier LtdObjectives Familial autoimmunity and polyautoimmunity represent extreme phenotypes ideal for identifying major genomic variants contributing to autoimmunity. Whole exome sequencing (WES) and linkage analysis are well suited for this purpose due to its strong resolution upon familial segregation patterns of functional protein coding and splice variants. The primary objective of this study was to identify potentially autoimmune causative variants using WES data from extreme pedigrees segregating polyautoimmunity phenotypes. Methods DNA of 47 individuals across 10 extreme pedigrees, ascertained from probands affected with polyautoimmunity and familial autoimmunity, were selected for WES. Variant calls were obtained through Genome Analysis Toolkit. Filtration and prioritization framework to identify mutation(s) were applied, and later implemented for genetic linkage analysis. Sanger sequencing corroborated variants with significant linkage. Results Novel and mostly rare variants harbored in SRA1, MLL4, ABCB8, DHX34 and PLAUR showed significant linkage (LOD scores are >3.0). The strongest signal was in SRA1, with a LOD score of 5.48. Network analyses indicated that SRA1, PLAUR and ABCB8 contribute to regulation of apoptotic processes. Conclusions Novel and rare variants in genetic linkage with polyautoimmunity were identified throughout WES. Genes harboring these variants might be major players of autoimmunity.",
author = "Angad Johar and Sarmiento-Monroy, {Juan C.} and Adriana Rojas-Villarraga and Silva-Lara, {Maria F.} and Patel, {Hardip R.} and Mantilla, {Ruben D.} and Velez, {Jorge I.} and Schulte, {Klaus Martin} and Claudio Mastronardi and Mauricio Arcos-Burgos and Anaya, {Juan Manuel}",
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Johar, A, Sarmiento-Monroy, JC, Rojas-Villarraga, A, Silva-Lara, MF, Patel, HR, Mantilla, RD, Velez, JI, Schulte, KM, Mastronardi, C, Arcos-Burgos, M & Anaya, JM 2016, 'Definition of mutations in polyautoimmunity', Journal of Autoimmunity, pp. 65-72. https://doi.org/10.1016/j.jaut.2016.05.003

Definition of mutations in polyautoimmunity. / Johar, Angad; Sarmiento-Monroy, Juan C.; Rojas-Villarraga, Adriana; Silva-Lara, Maria F.; Patel, Hardip R.; Mantilla, Ruben D.; Velez, Jorge I.; Schulte, Klaus Martin; Mastronardi, Claudio; Arcos-Burgos, Mauricio; Anaya, Juan Manuel.

En: Journal of Autoimmunity, 01.08.2016, p. 65-72.

Resultado de la investigación: Contribución a RevistaArtículo

TY - JOUR

T1 - Definition of mutations in polyautoimmunity

AU - Johar, Angad

AU - Sarmiento-Monroy, Juan C.

AU - Rojas-Villarraga, Adriana

AU - Silva-Lara, Maria F.

AU - Patel, Hardip R.

AU - Mantilla, Ruben D.

AU - Velez, Jorge I.

AU - Schulte, Klaus Martin

AU - Mastronardi, Claudio

AU - Arcos-Burgos, Mauricio

AU - Anaya, Juan Manuel

PY - 2016/8/1

Y1 - 2016/8/1

N2 - © 2016 Elsevier LtdObjectives Familial autoimmunity and polyautoimmunity represent extreme phenotypes ideal for identifying major genomic variants contributing to autoimmunity. Whole exome sequencing (WES) and linkage analysis are well suited for this purpose due to its strong resolution upon familial segregation patterns of functional protein coding and splice variants. The primary objective of this study was to identify potentially autoimmune causative variants using WES data from extreme pedigrees segregating polyautoimmunity phenotypes. Methods DNA of 47 individuals across 10 extreme pedigrees, ascertained from probands affected with polyautoimmunity and familial autoimmunity, were selected for WES. Variant calls were obtained through Genome Analysis Toolkit. Filtration and prioritization framework to identify mutation(s) were applied, and later implemented for genetic linkage analysis. Sanger sequencing corroborated variants with significant linkage. Results Novel and mostly rare variants harbored in SRA1, MLL4, ABCB8, DHX34 and PLAUR showed significant linkage (LOD scores are >3.0). The strongest signal was in SRA1, with a LOD score of 5.48. Network analyses indicated that SRA1, PLAUR and ABCB8 contribute to regulation of apoptotic processes. Conclusions Novel and rare variants in genetic linkage with polyautoimmunity were identified throughout WES. Genes harboring these variants might be major players of autoimmunity.

AB - © 2016 Elsevier LtdObjectives Familial autoimmunity and polyautoimmunity represent extreme phenotypes ideal for identifying major genomic variants contributing to autoimmunity. Whole exome sequencing (WES) and linkage analysis are well suited for this purpose due to its strong resolution upon familial segregation patterns of functional protein coding and splice variants. The primary objective of this study was to identify potentially autoimmune causative variants using WES data from extreme pedigrees segregating polyautoimmunity phenotypes. Methods DNA of 47 individuals across 10 extreme pedigrees, ascertained from probands affected with polyautoimmunity and familial autoimmunity, were selected for WES. Variant calls were obtained through Genome Analysis Toolkit. Filtration and prioritization framework to identify mutation(s) were applied, and later implemented for genetic linkage analysis. Sanger sequencing corroborated variants with significant linkage. Results Novel and mostly rare variants harbored in SRA1, MLL4, ABCB8, DHX34 and PLAUR showed significant linkage (LOD scores are >3.0). The strongest signal was in SRA1, with a LOD score of 5.48. Network analyses indicated that SRA1, PLAUR and ABCB8 contribute to regulation of apoptotic processes. Conclusions Novel and rare variants in genetic linkage with polyautoimmunity were identified throughout WES. Genes harboring these variants might be major players of autoimmunity.

U2 - 10.1016/j.jaut.2016.05.003

DO - 10.1016/j.jaut.2016.05.003

M3 - Article

C2 - 27209085

SP - 65

EP - 72

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

ER -

Johar A, Sarmiento-Monroy JC, Rojas-Villarraga A, Silva-Lara MF, Patel HR, Mantilla RD y otros. Definition of mutations in polyautoimmunity. Journal of Autoimmunity. 2016 ago 1;65-72. https://doi.org/10.1016/j.jaut.2016.05.003