Whole-exome sequencing provides a cost-effective means to sequence protein coding regions within the genome, which are significantly enriched for etiological variants. We describe a panel of single nucleotide polymorphisms (SNPs) to facilitate the validation of data provenance in whole-exome sequencing studies. This is particularly significant where multiple processing steps necessitate transfe...

BACKGROUND Whole exome sequencing is a powerful technique for Mendelian disease gene discovery. However, variant prioritization remains a challenge. We applied whole exome sequencing to identify the causal variant in a large family with familial dilated cardiomyopathy of unknown pathogenesis. METHODS AND RESULTS A large family with autosomal dominant, familial dilated cardiomyopathy was ident...

The report by Stone et al in this issue (available at www.aaojournal.org/article/S0161-6420(17)30460-8/fulltext;) is a timely reminder of the revolution under way in molecular genetic testing for inherited retinal disease (IRD). The new approach to testing involves the use of next-generation sequencing (NGS), a term used to describe a number of different technologies that use a common strategy ...

Copy number alterations (CNA) are common events occurring in leukaemias and solid tumors. Comparative Genome Hybridization (CGH) is actually the gold standard technique to analyze CNAs; however, CGH analysis requires dedicated instruments and is able to perform only low resolution Loss of Heterozygosity (LOH) analyses. Here we present CEQer (Comparative Exome Quantification analyzer), a new gra...

Spontaneously arising mouse mutations have served as the foundation for understanding gene function for more than 100 years. We have used exome sequencing in an effort to identify the causative mutations for 172 distinct, spontaneously arising mouse models of Mendelian disorders, including a broad range of clinically relevant phenotypes. To analyze the resulting data, we developed an analytics ...

BACKGROUND Colorectal cancer (CRC) in densely affected families without Lynch Syndrome may be due to mutations in undiscovered genetic loci. Familial linkage analyses have yielded disparate results; the use of exome sequencing in coding regions may identify novel segregating variants. METHODS We completed exome sequencing on 40 affected cases from 16 multicase pedigrees to identify novel loci...

BACKGROUND De novo mutations are a frequent cause of disorders related to brain development. We report the results of screening patients diagnosed with both epilepsy and intellectual disability (ID) using exome sequencing to identify known and new causative de novo mutations relevant to these conditions. METHODS Exome sequencing was performed on 39 patient-parent trios to identify de novo mut...

PURPOSE To investigate the efficacy of targeted exome sequencing for mutational screening of Japanese patients with cone dystrophy (CD) or cone-rod dystrophy (CRD). METHODS DNA samples from 43 Japanese patients with CD or CRD were sequenced using an exome-sequencing panel targeting all 193 known inherited eye disease genes and next-generation sequencing methodologies. Subsequently, candidate ...