title: Multiphasic analysis of whole exome sequencing data identifies a novel mutation of ACTG1 in a nonsyndromic hearing loss family.
abstract: BACKGROUND
  The genetic heterogeneity of sensorineural hearing loss is a major hurdle to the efficient discovery of disease-causing genes. We designed a multiphasic analysis of copy number variation (CNV), linkage, and single nucleotide variation (SNV) of whole exome sequencing (WES) data for the efficient discovery of mutations causing nonsyndromic hearing loss (NSHL).
  
  
  RESULTS
  From WES data, we identified five distinct CNV loci from a NSHL family, but they were not co-segregated among patients. Linkage analysis based on SNVs identified six candidate loci (logarithm of odds [LOD] >1.5). We selected 15 SNVs that co-segregated with NSHL in the family, which were located in six linkage candidate loci. Finally, the novel variant p.M305T in ACTG1 (DFNA20/26) was selected as a disease-causing variant.
  
  
  CONCLUSIONS
  Here, we present a multiphasic CNV, linkage, and SNV analysis of WES data for the identification of a candidate mutation causing NSHL. Our stepwise, multiphasic approach enabled us to expedite the discovery of disease-causing variants from a large number of patient variants.
authors.affiliation: Department of Biomedical Sciences, Seoul National University GraduateSchool, Seoul 110-799, Korea.
authors.forename: Gibeom
authors.initials: G
authors.lastname: Park
authors.forename: Jungsoo
authors.initials: J
authors.lastname: Gim
authors.forename: Ah Reum
authors.initials: AR
authors.lastname: Kim
authors.forename: Kyu-Hee
authors.initials: KH
authors.lastname: Han
authors.forename: Hyo-Sang
authors.initials: HS
authors.lastname: Kim
authors.forename: Seung-Ha
authors.initials: SH
authors.lastname: Oh
authors.forename: Taesung
authors.initials: T
authors.lastname: Park
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.forename: Byung Yoon
authors.initials: BY
authors.lastname: Choi
mesh_terms: D001483:Base Sequence; D018360:Crystallography, X-Ray; D056915:DNA Copy Number Variations / Q000235:genetics*; D059472:Exome / Q000235:genetics; D008040:Genetic Linkage; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology; D006801:Humans; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA