-
Article
Open AccessAdvancing access to genome sequencing for rare genetic disorders: recent progress and call to action
-
Article
Open AccessEvidence review and considerations for use of first line genome sequencing to diagnose rare genetic disorders
Early use of genome sequencing (GS) in the diagnostic odyssey can reduce suffering and improve care, but questions remain about which patient populations are most amenable to GS as a first-line diagnostic test...
-
Article
Open AccessPublisher Correction: Cyrius: accurate CYP2D6 genoty** using whole-genome sequencing data
-
Article
Open AccessBest practices for the interpretation and reporting of clinical whole genome sequencing
Whole genome sequencing (WGS) shows promise as a first-tier diagnostic test for patients with rare genetic disorders. However, standards addressing the definition and deployment practice of a best-in-class tes...
-
Article
Open AccessThe diagnostic trajectory of infants and children with clinical features of genetic disease
We characterized US pediatric patients with clinical indicators of genetic diseases, focusing on the burden of disease, utilization of genetic testing, and cost of care. Curated lists of diagnosis, procedure, ...
-
Article
Open AccessCyrius: accurate CYP2D6 genoty** using whole-genome sequencing data
Responsible for the metabolism of ~21% of clinically used drugs, CYP2D6 is a critical component of personalized medicine initiatives. Genoty** CYP2D6 is challenging due to sequence similarity with its pseudogen...
-
Article
Open AccessBest practices for the analytical validation of clinical whole-genome sequencing intended for the diagnosis of germline disease
Whole-genome sequencing (WGS) has shown promise in becoming a first-tier diagnostic test for patients with rare genetic disorders; however, standards addressing the definition and deployment practice of a best...
-
Article
Open AccessExpansionHunter Denovo: a computational method for locating known and novel repeat expansions in short-read sequencing data
Repeat expansions are responsible for over 40 monogenic disorders, and undoubtedly more pathogenic repeat expansions remain to be discovered. Existing methods for detecting repeat expansions in short-read sequ...
-
Article
Open AccessClinical whole genome sequencing as a first-tier test at a resource-limited dysmorphology clinic in Mexico
Patients with rare, undiagnosed, or genetic disease (RUGD) often undergo years of serial testing, commonly referred to as the “diagnostic odyssey”. Patients in resource-limited areas face even greater challeng...
-
Article
Open AccessDiverse RNA interference strategies in early-branching metazoans
Micro RNAs (miRNAs) and piwi interacting RNAs (piRNAs), along with the more ancient eukaryotic endogenous small interfering RNAs (endo-siRNAs) constitute the principal components of the RNA interference (RNAi)...
-
Article
Open AccessDNA methylation regulates discrimination of enhancers from promoters through a H3K4me1-H3K4me3 seesaw mechanism
DNA methylation at promoters is largely correlated with inhibition of gene expression. However, the role of DNA methylation at enhancers is not fully understood, although a crosstalk with chromatin marks is ex...
-
Article
Open AccessX-linked hypomyelination with spondylometaphyseal dysplasia (H-SMD) associated with mutations in AIFM1
An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent g...
-
Article
Open AccessRecessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III
A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causa...
-
Article
Quantitative gene profiling of long noncoding RNAs with targeted RNA sequencing
CaptureSeq was used to quantitatively profile transcripts with low expression, resulting in a catalog of long noncoding RNA expression in 20 human tissues.
-
Article
Correction: Corrigendum: Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy
Nat. Genet. 47, 73–77 (2015); published online 24 November 2014; corrected after print 6 February 2015 In the version of this article initially published, in Figure 2a, the order of the protein alterations for...
-
Article
Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy
Cas Simons, Ryan Taft and colleagues report the identification of KCNH1 mutations in six individuals with Temple-Baraitser syndrome (TBS). Electrophysiological measurements of cells expressing mutant KCNH1 channe...
-
Article
Open AccessIdentification of nuclear-enriched miRNAs during mouse granulopoiesis
MicroRNAs (miRNAs) are coordinators of cellular differentiation, including granulopoiesis. Although differential expression of many miRNAs is associated with the maturation of granulocytes, analysis of differe...
-
Article
Targeted sequencing for gene discovery and quantification using RNA CaptureSeq
RNA sequencing (RNAseq) samples the majority of expressed genes infrequently, owing to the large size, complex splicing and wide dynamic range of eukaryotic transcriptomes. This results in sparse sequencing co...
-
Article
Open AccessInformation compression exploits patterns of genome composition to discriminate populations and highlight regions of evolutionary interest
Genomic information allows population relatedness to be inferred and selected genes to be identified. Single nucleotide polymorphism microarray (SNP-chip) data, a proxy for genome composition, contains pattern...
-
Article
Open AccessSystematic interrogation of the Conus marmoreus venom duct transcriptome with ConoSorter reveals 158 novel conotoxins and 13 new gene superfamilies
Conopeptides, often generically referred to as conotoxins, are small neurotoxins found in the venom of predatory marine cone snails. These molecules are highly stable and are able to efficiently and selectivel...
