title: Non-syndromic hearing loss gene identification: A brief history and glimpse into the future.
abstract: From the first identified non-syndromic hearing loss gene in 1995, to those discovered in present day, the field of human genetics has witnessed an unparalleled revolution that includes the completion of the Human Genome Project in 2003 to the $1000 genome in 2014. This review highlights the classical and cutting-edge strategies for non-syndromic hearing loss gene identification that have been used throughout the twenty year history with a special emphasis on how the innovative breakthroughs in next generation sequencing technology have forever changed candidate gene approaches. The simplified approach afforded by next generation sequencing technology provides a second chance for the many linked loci in large and well characterized families that have been identified by linkage analysis but have presently failed to identify a causative gene. It also discusses some complexities that may restrict eventual candidate gene discovery and calls for novel approaches to answer some of the questions that make this simple Mendelian disorder so intriguing.
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany. Electronic address: barbara.vona@uni-wuerzburg.de.
authors.forename: Barbara
authors.initials: B
authors.lastname: Vona
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany.
authors.forename: Indrajit
authors.initials: I
authors.lastname: Nanda
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany.
authors.forename: Michaela A H
authors.initials: MA
authors.lastname: Hofrichter
authors.affiliation: Comprehensive Hearing Center, Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Surgery, University Hospital, Würzburg, Germany.
authors.forename: Wafaa
authors.initials: W
authors.lastname: Shehata-Dieler
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Haaf
mesh_terms: D000072259:Connexin 26; D017630:Connexins; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D034381:Hearing Loss / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26
keywords: Copy number variation (CNV); Deafness; GJB2; Homozygosity mapping; Linkage analysis; Missing heritability; Next generation sequencing (NGS); Non-syndromic hearing loss (NSHL); Positional cloning