title: Reducing the exome search space for mendelian diseases using genetic linkage analysis of exome genotypes.
abstract: Many exome sequencing studies of Mendelian disorders fail to optimally exploit family information. Classical genetic linkage analysis is an effective method for eliminating a large fraction of the candidate causal variants discovered, even in small families that lack a unique linkage peak. We demonstrate that accurate genetic linkage mapping can be performed using SNP genotypes extracted from exome data, removing the need for separate array-based genotyping. We provide software to facilitate such analyses.
authors.affiliation: Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia. katsmith@wehi.edu.au
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Smith
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Bromhead
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hildebrand
authors.forename: A Eliot
authors.initials: AE
authors.lastname: Shearer
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lockhart
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Leventer
authors.forename: George
authors.initials: G
authors.lastname: McGillivray
authors.forename: David J
authors.initials: DJ
authors.lastname: Amor
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Smith
authors.forename: Melanie
authors.initials: M
authors.lastname: Bahlo
mesh_terms: D001483:Base Sequence; D002877:Chromosomes, Human / Q000235:genetics; D059472:Exome; D005787:Gene Frequency; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D008040:Genetic Linkage; D015894:Genome, Human; D005838:Genotype; D060005:Genotyping Techniques; D060148:HapMap Project; D006801:Humans; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012984:Software