Figure 1. Gene discovery in autosomal recessive auditory neuropathy.

We mapped and identified the gene using a single sibship which in isolated populations such as the Old Order Amish can be accomplished with as few as 2 affected individuals, then subsequently identified additional affected individuals from separate sibships. A) We performed a genome-wide homozygosity mapping study using Affymetrix GeneChip Mapping 10K SNP Arrays with a single Old Order Amish sibship with three affected. Two large, shared blocks of homozygosity were identified on chromosomes 13 and 14. However, the location score was highest for the chromosome 13q31 region and a subsequent affected child in the family was not homozygous for the chromosome 14 SNP markers. The common homozygous segment was flanked by SNPs rs722023 and rs958373, spanned 9.3 Mb and contained 33 known or predicted genes based on NCBI annotations. B) Sanger sequencing of the SLITRK6 gene revealed homozygosity for a nonsense variant in exon 2 in all affected individuals (c.1240C>T). The three panels depict sequencing of a normal homozygote, a carrier, and a mutation homozygote, respectively.