Leukodystrophies and genetic leukoencephalopathies are a rare group of disorders leading to progressive degeneration of cerebral white matter. They are associated with a spectrum of clinical phenotypes dominated by dementia, psychiatric changes, movement disorders and upper motor neuron signs. Mutations in at least 60 genes can lead to leukoencephalopathy with often overlapping clinical and rad...

We explored the feasibility of studying loss of heterozygosity (LOH) by using exome sequencing and compared the differences in genetic LOH between primary breast tumors and metastatic lesions. Exome sequencing was conducted to investigate the genetic LOH in the peripheral blood, a primary tumor, and a metastatic lesion from the same patient. LOH was observed in 30 and 48 chromosomal loci of the...

BACKGROUND Inherited cardiac conduction diseases (CCD) are rare but are caused by mutations in a myriad of genes. Recently, whole-exome sequencing has successfully led to the identification of causal mutations for rare monogenic Mendelian diseases. OBJECTIVE To investigate the genetic background of a family affected by inherited CCD. METHODS AND RESULTS We used whole-exome sequencing to stu...

Motivations The recent advances in the technologies and strategies for DNA sequencing have dramatically facilitated the identification of novel human genes associated with rare and common diseases [1]. However novel methods are needed to identify high-quality variations among all the ones identified in a single experiment. The most successful approach to identify disease-causing mutations consi...

Summary: Although the 1000 Genomes haplotypes are the most commonly used reference panel for imputation, medical sequencing projects are generating large alternate sets of sequenced samples. Imputation in African Americans using 3384 haplotypes from the Exome Sequencing Project, compared with 2184 haplotypes from 1000 Genomes Project, increased effective sample size by 8.3–11.4% for coding vari...

MOTIVATION Exome sequencing technologies have transformed the field of Mendelian genetics and allowed for efficient detection of genomic variants in protein-coding regions. The target enrichment process that is intrinsic to exome sequencing is inherently imperfect, generating large amounts of unintended off-target sequence. Off-target data are characterized by very low and highly heterogeneous ...

Prostate cancer is a leading cause of cancer-related death in Western men. Our understanding of the genetic alterations associated with disease predisposition, development, progression, and therapy response is rapidly improving, at least in part, owing to the development of next-generation sequencing technologies. Large advances have been made in our understanding of the genetics of prostate ca...

Genomic technologies, such as whole-exome sequencing, are a powerful tool in genetic research. Such testing yields a great deal of incidental medical information, or medical information not related to the primary research target. We describe the management of incidental medical information derived from whole-exome sequencing in the research context. We performed whole-exome sequencing on a mono...

BACKGROUND Whole-exome sequencing is a diagnostic approach for the identification of molecular defects in patients with suspected genetic disorders. METHODS We developed technical, bioinformatic, interpretive, and validation pipelines for whole-exome sequencing in a certified clinical laboratory to identify sequence variants underlying disease phenotypes in patients. RESULTS We present data...

Protein coding genes constitute approximately 1% of the human genome but harbor 85% of the mutations with large effects on disease-related traits. Therefore, efficient strategies for selectively sequencing complete coding regions (i.e., "whole exome") have the potential to contribute our understanding of human diseases. We used a method for whole-exome sequencing coupling Agilent whole-exome ca...