title: A next-generation sequencing gene panel (MiamiOtoGenes) for comprehensive analysis of deafness genes.
abstract: Extreme genetic heterogeneity along with remarkable variation in the distribution of causative variants across in different ethnicities makes single gene testing inefficient for hearing loss. We developed a custom capture/next-generation sequencing gene panel of 146 known deafness genes with a total target size of approximately 1 MB. The genes were identified by searching databases including Hereditary Hearing Loss Homepage, the Human Genome Mutation Database (HGMD), Online Mendelian Inheritance in Man (OMIM) and most recent peer-reviewed publications related to the genetics of deafness. The design covered all coding exons, UTRs and 25 bases of intronic flanking sequences for each exon. To validate our panel, we used 6 positive controls with variants in known deafness genes and 8 unsolved samples from individuals with hearing loss. Mean coverage of the targeted exons was 697X. On average, each sample had 99.8%, 96.2% and 92.7% of the targeted region coverage of 1X, 50X and 100X reads, respectively. Analysis detected all known variants in nuclear genes. These results prove the accuracy and reliability of the custom capture experiment.
authors: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors: Demet
authors: D
authors: Tekin
authors: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors: Denise
authors: D
authors: Yan
authors: Dr. John T. Macdonald Foundation Department of Human Genetics, and John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL 33136, USA.
authors: Guney
authors: G
authors: Bademci
authors: Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Yong
authors: Y
authors: Feng
authors: Dr. John T. Macdonald Foundation Department of Human Genetics, and John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL 33136, USA.
authors: Shengru
authors: S
authors: Guo
authors: Dr. John T. Macdonald Foundation Department of Human Genetics, and John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL 33136, USA.
authors: Joseph
authors: J
authors: Foster
authors: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.|Dr. John T. Macdonald Foundation Department of Human Genetics, and John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL 33136, USA.
authors: Susan
authors: S
authors: Blanton
authors: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.|Dr. John T. Macdonald Foundation Department of Human Genetics, and John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL 33136, USA.
authors: Mustafa
authors: M
authors: Tekin
authors: Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.|Dr. John T. Macdonald Foundation Department of Human Genetics, and John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL 33136, USA.|Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Xuezhong
authors: X
authors: Liu
mesh_terms: D019295:Computational Biology; D030541:Databases, Genetic; D003638:Deafness / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005091:Exons; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006309:Hearing / Q000235:genetics*; D040941:Heredity; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D010375:Pedigree; D010641:Phenotype; D015203:Reproducibility of Results; D020506:Untranslated Regions
chemical_list: D005819:Genetic Markers; D020506:Untranslated Regions
keywords: Custom capture; Deafness; Gene; Hearing loss; Next generation sequencing