title: Using familial information for variant filtering in high-throughput sequencing studies.
abstract: High-throughput sequencing studies (HTS) have been highly successful in identifying the genetic causes of human disease, particularly those following Mendelian inheritance. Many HTS studies to date have been performed without utilizing available family relationships between samples. Here, we discuss the many merits and occasional pitfalls of using identity by descent information in conjunction with HTS studies. These methods are not only applicable to family studies but are also useful in cohorts of apparently unrelated, 'sporadic' cases and small families underpowered for linkage and allow inference of relationships between individuals. Incorporating familial/pedigree information not only provides powerful filtering options for the extensive variant lists that are usually produced by HTS but also allows valuable quality control checks, insights into the genetic model and the genotypic status of individuals of interest. In particular, these methods are valuable for challenging discovery scenarios in HTS analysis, such as in the study of populations poorly represented in variant databases typically used for filtering, and in the case of poor-quality HTS data.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia, bahlo@wehi.edu.au.
authors.forename: Melanie
authors.initials: M
authors.lastname: Bahlo
authors.forename: Rick
authors.initials: R
authors.lastname: Tankard
authors.forename: Vesna
authors.initials: V
authors.lastname: Lukic
authors.forename: Karen L
authors.initials: KL
authors.lastname: Oliver
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Smith
mesh_terms: D005190:Family; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D060148:HapMap Project; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008957:Models, Genetic; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software