title: Rapid Detection of Rare Deleterious Variants by Next Generation Sequencing with Optional Microarray SNP Genotype Data.
abstract: Autozygosity mapping is a powerful technique for the identification of rare, autosomal recessive, disease-causing genes. The ease with which this category of disease gene can be identified has greatly increased through the availability of genome-wide SNP genotyping microarrays and subsequently of exome sequencing. Although these methods have simplified the generation of experimental data, its analysis, particularly when disparate data types must be integrated, remains time consuming. Moreover, the huge volume of sequence variant data generated from next generation sequencing experiments opens up the possibility of using these data instead of microarray genotype data to identify disease loci. To allow these two types of data to be used in an integrated fashion, we have developed AgileVCFMapper, a program that performs both the mapping of disease loci by SNP genotyping and the analysis of potentially deleterious variants using exome sequence variant data, in a single step. This method does not require microarray SNP genotype data, although analysis with a combination of microarray and exome genotype data enables more precise delineation of disease loci, due to superior marker density and distribution.
authors.affiliation: School of Medicine, University of Leeds, Leeds, United Kingdom.|Yorkshire Regional Genetics Service, St James's University Hospital, Leeds, United Kingdom.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Watson
authors.affiliation: School of Medicine, University of Leeds, Leeds, United Kingdom.|Yorkshire Regional Genetics Service, St James's University Hospital, Leeds, United Kingdom.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Crinnion
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Gurgel-Gianetti
authors.affiliation: School of Medicine, University of Leeds, Leeds, United Kingdom.
authors.forename: Sally M
authors.initials: SM
authors.lastname: Harrison
authors.affiliation: School of Medicine, University of Leeds, Leeds, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Daly
authors.affiliation: School of Medicine, University of Leeds, Leeds, United Kingdom.
authors.forename: Agne
authors.initials: A
authors.lastname: Antanavicuite
authors.affiliation: School of Medicine, University of Leeds, Leeds, United Kingdom.
authors.forename: Carolina
authors.initials: C
authors.lastname: Lascelles
authors.affiliation: School of Medicine, University of Leeds, Leeds, United Kingdom.
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Markham
authors.affiliation: Laboratory of Clinical Genomics, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.|GENE-Nucleo de Genetica Medica de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Sergio D J
authors.initials: SD
authors.lastname: Pena
authors.affiliation: School of Medicine, University of Leeds, Leeds, United Kingdom.|Yorkshire Regional Genetics Service, St James's University Hospital, Leeds, United Kingdom.
authors.forename: David T
authors.initials: DT
authors.lastname: Bonthron
authors.affiliation: School of Medicine, University of Leeds, Leeds, United Kingdom.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Carr
mesh_terms: D002874:Chromosome Mapping / Q000379:methods; D019295:Computational Biology / Q000379:methods; D003241:Consanguinity; D059472:Exome; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D040582:Inheritance Patterns; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012984:Software
keywords: autozygosity mapping; exome; next generation sequencing; software