PMC

Pedigree diagrams of 8 Korean families with autosomal dominant hearing loss. An asterisk in the upper right corner of the symbol indicates an individual whose genomic DNA was analyzed by targeted sequencing. Co-segregation of the candidate variations detected in the targeted sequencing and the phenotype of hearing loss was confirmed via Sanger sequencing of DNA from the individuals marked by a bar. Squares and circles represent males and females, respectively. Filled symbols represent affected individuals, and slashes indicate deceased individuals.

The identification of 5 non-synonymous variations showing co-segregation with hearing loss in affected families.Top: Visualization of individual sequencing reads covering the mutations in the genes. The actual read depth for these mutated nucleotides ranged between 46× and 442×. Blue and green reads represent the positive and negative strands, respectively, and the red bases represent bases that differ from the reference sequence (black). Middle: Verification of each variation by Sanger sequencing. All 5 of the variations marked by black arrows are single nucleotide substitutions leading to early truncation of the polypeptide or a change in the amino acid. Bottom: A comparison of amino acid sequences of each gene in multiple vertebrate species. The asterisks indicate the amino acid substituted by the mutation. A single line between the aligned amino acids indicates that there is no base in the aligned species, and a double line indicates that the aligned species has one or more bases that cannot be aligned in the gap region. The majority of the mutated amino acids are strongly conserved across the 9 different species shown.