Definition of mutations in polyautoimmunity
| Autor: | Hardip R. Patel, Maria Fernanda Silva-Lara, Angad S. Johar, Juan-Manuel Anaya, Juan Camilo Sarmiento-Monroy, Klaus-Martin Schulte, Adriana Rojas-Villarraga, Claudio A. Mastronardi, Mauricio Arcos-Burgos, Rubén D. Mantilla, Jorge I. Vélez |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Proband Male Carrier protein Pedigree chart Autoimmunity Gene sequence Procedures Steroid receptor RNA activator Receptors Immunology and Allergy Exome Gene Regulatory Networks PLAUR protein Exome sequencing Priority journal Genetics Sanger sequencing Linkage Gene regulatory network Extreme phenotype MLL4 protein Genomics Genetic linkage Pedigree DNA-Binding Proteins Phenotype Urokinase Plasminogen Activator symbols Network analysis Female ABC transporter Urokinase receptor Sequence Analysis RNA Helicases Human RNA helicase Immunology DNA sequence Biology Pedigree analysis DHX34 protein Article Receptors Urokinase Plasminogen Activator 03 medical and health sciences symbols.namesake Humans Genetic Predisposition to Disease Genetic variation Gene mutation Lod score Linkage (software) Family Health Base Sequence Genetic predisposition DNA Histone-Lysine N-Methyltransferase Sequence Analysis DNA Polyautoimmunity DNA binding protein 030104 developmental biology Mutation ATP-Binding Cassette Transporters Lod Score Familial autoimmunity Carrier Proteins Nucleotide sequence |
| Zdroj: | Repositorio EdocUR-U. Rosario Universidad del Rosario instacron:Universidad del Rosario |
| ISSN: | 1095-9157 |
| Popis: | Objectives 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. |
| Databáze: | OpenAIRE |
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