title: Candidate gene discovery in autoimmunity by using extreme phenotypes, next generation sequencing and whole exome capture.
abstract: Whole exome sequencing (WES) is a widely used strategy for detection of protein coding and splicing variants associated with inherited diseases. Many studies have shown that the strategy has been broad and proficient due to its ability in detecting a high proportion of disease causing variants, using only a small portion of the genome. In this review we outline the main steps involved in WES, the comprehensive analysis of the massive data obtained including the genomic capture, amplification, sequencing, alignment, curating, filtering and genetic analysis to determine the presence of candidate variants with potential pathogenic/functional effect. Further, we propose that the multiple autoimmune syndrome, an extreme phenotype of autoimmune disorders, is a very well suited trait to tackle genomic variants of major effect underpinning the lost of self-tolerance.
authors.affiliation: Genomics and Predictive Medicine, Genome Biology Department, John Curtin School of Medical Research, ANU College of Medicine, Biology & Environment, The Australian National University, Canberra, ACT, Australia.
authors.forename: Angad S
authors.initials: AS
authors.lastname: Johar
authors.affiliation: Centre for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia. Electronic address: juan.anaya@urosario.edu.co.
authors.forename: Juan-Manuel
authors.initials: JM
authors.lastname: Anaya
authors.affiliation: Immunogenomics and Bioinformatics Group, Immunology Department, John Curtin School of Medical Research, ANU College of Medicine, Biology & Environment, The Australian National University, Canberra, ACT, Australia.
authors.forename: Dan
authors.initials: D
authors.lastname: Andrews
authors.affiliation: Genome Discovery Unit, Genome Biology Department, John Curtin School of Medical Research, ANU College of Medicine, Biology & Environment, The Australian National University, Canberra, ACT, Australia.
authors.forename: Hardip R
authors.initials: HR
authors.lastname: Patel
authors.affiliation: Immunogenomics and Bioinformatics Group, Immunology Department, John Curtin School of Medical Research, ANU College of Medicine, Biology & Environment, The Australian National University, Canberra, ACT, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Field
authors.affiliation: Immunogenomics and Bioinformatics Group, Immunology Department, John Curtin School of Medical Research, ANU College of Medicine, Biology & Environment, The Australian National University, Canberra, ACT, Australia.
authors.forename: Chris
authors.initials: C
authors.lastname: Goodnow
authors.affiliation: Genomics and Predictive Medicine, Genome Biology Department, John Curtin School of Medical Research, ANU College of Medicine, Biology & Environment, The Australian National University, Canberra, ACT, Australia. Electronic address: Mauricio.Arcos-Burgos@anu.edu.au.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Arcos-Burgos
mesh_terms: D015551:Autoimmunity; D059472:Exome; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D010641:Phenotype; D017422:Sequence Analysis, DNA
keywords: Multiple autoimmune syndrome; Next generation sequencing; Polyautoimmunity; Whole exome sequencing; Whole genome sequencing