A multiphasic analysis of WES data. WES data were analyzed for exon CNVs and SNVs. Fisher exact test on CNVs detected one exon segregating with NSHL on chr19 (top). Linkage analysis with SNVs called by Exome-seq identified six disease-linked “hot spots” on chr3, chr11, chr13, chr14, chr16, and chr17 (middle). Segregation analysis independently identified 15 SNVs co-segregating with NSHL (green dots). Among them, a novel variant resulting in p.M305T, in ACTG1 on chr17 was validated with Sanger sequencing (red dot). Linkage analysis was also performed with SNP microarray by adding three more subjects in the family. Not only were similar “hot spots” detected, adding more subjects in the analysis enhanced the true peak (red arrow) (bottom).
Park et al. BMC Genomics 2013 14:191 doi:10.1186/1471-2164-14-191