Human leukocyte antigen (HLA) typing at the allelic level can in theory be achieved using whole exome sequencing (exome-seq) data with no added cost but has been hindered by its computational challenge. We developed ATHLATES, a program that applies assembly, allele identification and allelic pair inference to short read sequences, and applied it to data from Illumina platforms. In 15 data sets ...

We present a sibling pair with Leigh-like disease, progressive hypotonia, regression, and chronic encephalopathy. Whole exome sequencing in the younger sibling demonstrated a homozygous thiamine pyrophosphokinase (TPK) mutation. Initiation of high dose thiamine, niacin, biotin, α-lipoic acid and ketogenic diet in this child demonstrated improvement in neurologic function and re-attainment of pr...

OBJECTIVE To determine the genetic basis of an unexplained multisystem neurological disorder affecting 2 siblings. DESIGN Case reports and whole-exome DNA sequencing. SETTING Neurogenetics clinic, Institute of Genetic Medicine, Newcastle upon Tyne, England. PATIENTS Two adult siblings with a sensorimotor neuropathy, ataxia, and spasticity. MAIN OUTCOME MEASURES Clinical, neurophysiologi...

The study of inborn errors of immunity is based on a comprehensive clinical description of the patient's phenotype and the elucidation of the underlying molecular mechanisms and their genetic etiology. Deciphering the pathogenesis is key to genetic counseling and the development of targeted therapy. This review shows the power of whole-exome sequencing in detecting inborn errors of immunity alo...

Exome sequencing identified compound heterozygous mutations in the recently discovered mitochondrial methionyl-tRNA formyltransferase (MTFMT) gene in two sisters with mild Leigh syndrome and combined respiratory chain deficiency. The mutations lead to undetectable levels of the MTFMT protein. Blue native polyacrylamide gel electrophoresis showed decreased complexes I and IV, and additional prod...

James Zou, Gregory Valiant, Paul Valiant, Konrad Karczewski, Siu On Chan, Kaitlin Samocha, Monkol Lek, Exome Aggregation Consortium, Shamil Sunyaev, Mark Daly, Daniel G MacArthur Microsoft Research, One Memorial Drive, Cambridge MA, USA Computer Science Department, Stanford University, Palo Alto CA, USA Computer Science Department, Brown University, Providence RI, USA Analytic and Translational...

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...

Exome sequencing Genomic DNA was isolated using the Qiagen Blood/Tissue kit (Qiagen, Valencia, CA). Exome capture was performed with the Agilent SureSelect All-Exon v2 kit, and 100 bp paired-end library reads were generated on Illumina HiSeq 2000 to a 50-fold target average depth of coverage. Alignment of reads to the human genome was performed with DNAnexus (www.dnanexus.com) and bwa (Li and D...

X-linked Intellectual Disability (XLID) is a group of genetically heterogeneous disorders caused by mutations in genes on the X chromosome. Deleterious mutations in ~10% of X chromosome genes are implicated in causing XLID disorders in ~50% of known and suspected XLID families. The remaining XLID genes are expected to be rare and even private to individual families. To systematically identify t...