[Resistant hypertension - pheochromocytoma].

We report a case of a man with a 30-year history of treatment-resistant hypertension, hydropoiesis, tachycardic spells and dysgeusia. Despite repeated visits to the emergency department and work-up in an out-patient clinic, the diagnosis was unknown. Three years prior to remittance to an endocrinologist, the hypertension worsened, and he developed diabetes type-II.

Population-level deficit of homozygosity unveils CPSF3 as an intellectual disability syndrome gene.

Predicting the pathogenicity of biallelic missense variants can be challenging. Here, we use a deficit of observed homozygous carriers of missense variants, versus an expected number in a set of 153,054 chip-genotyped Icelanders, to identify potentially pathogenic genotypes. We follow three missense variants with a complete deficit of homozygosity and find that their pathogenic effect in homozygous state ranges from severe childhood disease to early embryonic lethality.

[Increased use of genetic health care in Iceland 2012-2017].

Introduction: A genetic counselling unit at Landspitali hospital (LSH) was established in 2006. Meanwhile, genetic testing has become an integral part of general health care. In this article we detail the outcome of genetic testing at the Department of Genetic and Molecular Medicine (DGM) at Landspitali over a five year period (2012-2017).

Molecular genetics of inherited retinal degenerations in Icelandic patients.

The study objective was to delineate the genetics of inherited retinal degenerations (IRDs) in Iceland, a small nation of 364.000 and a genetic isolate. Benefits include delineating novel pathogenic genetic variants and defining genetically homogenous patients as potential investigative molecular therapy candidates.

Web-based return of BRCA2 research results: one-year genetic counselling experience in Iceland.

There is an increased pressure to return results from research studies. In Iceland, deCODE Genetics has emphasised the importance of returning results to research participants, particularly the founder pathogenic BRCA2 variant; NM_000059.3:c.

Northern lights assay: a versatile method for comprehensive detection of DNA damage.

DNA damage assays have various limitations in types of lesions detected, sensitivity, specificity and samples that can be analyzed. The Northern Lights Assay (NLA) is based on 2D Strandness-Dependent Electrophoresis (2D-SDE), a technique that separates nucleic acids based on length, strandness, structure and conformation changes induced by damage. NLA is run on a microgel platform in 20-25 min.

Microgels and apparatus for PAGE of nucleic acids in one or two dimensions.

We describe a system for horizontal 1D or 2D PAGE comprising an apparatus and microgels. There is no buffer outside the gel, making handling and sample loading easy. Specially designed electrodes on all four sides allow 2D electrophoresis without gel rotation.

Counsellee's experience of cancer genetic counselling with pedigrees that automatically incorporate genealogical and cancer database information.

While pedigree drawing software is often utilised in genetic services, the use of genealogical databases in genetic counselling is unusual. This is mainly because of the unavailability of such databases in most countries. Electronically generated pedigrees used for cancer genetic counselling in Iceland create pedigrees that automatically incorporate information from a large, comprehensive genealogy database and nation-wide cancer registry.

Large-scale whole-genome sequencing of the Icelandic population.

Here we describe the insights gained from sequencing the whole genomes of 2,636 Icelanders to a median depth of 20×. We found 20 million SNPs and 1.5 million insertions-deletions (indels).

Variability of ethics education in laboratory medicine training programs: results of an international survey.

Background: Ethical considerations are increasingly important in medicine. We aimed to determine the mode and extent of teaching of ethics in training programs in clinical chemistry and laboratory medicine.

Methods: We developed an on-line survey of teaching in areas of ethics relevant to laboratory medicine.

Membrane transporters in a human genome-scale metabolic knowledgebase and their implications for disease.

Membrane transporters enable efficient cellular metabolism, aid in nutrient sensing, and have been associated with various diseases, such as obesity and cancer. Genome-scale metabolic network reconstructions capture genomic, physiological, and biochemical knowledge of a target organism, along with a detailed representation of the cellular metabolite transport mechanisms. Since the first reconstruction of human metabolism, Recon 1, published in 2007, progress has been made in the field of metabolite transport.

Impact of different ChIP-Seq protocols on DNA integrity and quality of bioinformatics analysis results.

Different ChIP-Seq protocols may have a significant impact on the final outcome in terms of quality, number and distribution of called peaks. Sample DNA undergoes a long procedure before the final sequencing step, and damaged DNA can result in excessive mismatches in the alignment with reference genome. In this letter, we present the effect of well-defined modifications (timing of formaldehyde crosslink reversal, brand of the sonicator) of standard ChIP-Seq protocol on parallel samples derived from the same cell line correlating the initial DNA quality control metrics to the final bioinformatics analysis results.

Iceland-genetic counseling services.

This brief report aims to give an overview of the history and current status of clinical genetics services in Iceland and specific genetic counseling considerations for Iceland's population. Presently, there are two part time medical geneticists and one full time genetic counselor with an MSc education from Cardiff, within the Department of Genetic and Molecular Medicine, based in Iceland's only tertiary healthcare facility, Landspitali, the National University Hospital. An oncologist (20 %) also contributes to the cancer genetic counseling service.

A community-driven global reconstruction of human metabolism.

Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven, consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared with its predecessors, the reconstruction has improved topological and functional features, including ∼2× more reactions and ∼1.

Importance of the efficiency of double-stranded DNA formation in cDNA synthesis for the imprecision of microarray expression analysis.

Background: The causes of imprecision in microarray expression analysis are poorly understood, limiting the use of this technology in molecular diagnostics. Two-dimensional strandness-dependent electrophoresis (2D-SDE) separates nucleic acid molecules on the basis of length and strandness, i.e.

The use of genealogy databases for risk assessment in genetic health service: a systematic review.

Unlabelled: The use of electronic genealogical databases facilitates the construction of accurate and extensive pedigrees for potential use in genetic services. Genealogy databases can be linked to specific disease databases, such as cancer registries, in order to increase the accuracy of pedigrees used, and inform the genetic risk assessment. To review the published literature on the use of genealogy databases to construct pedigrees for risk assessment in genetic health service, a systematic literature search was undertaken using 12 combined search terms to identify all relevant published articles.

A compendium of inborn errors of metabolism mapped onto the human metabolic network.

Inborn errors of metabolism (IEMs) are hereditary metabolic defects, which are encountered in almost all major metabolic pathways occurring in man. Many IEMs are screened for in neonates through metabolomic analysis of dried blood spot samples. To enable the mapping of these metabolomic data onto the published human metabolic reconstruction, we added missing reactions and pathways involved in acylcarnitine (AC) and fatty acid oxidation (FAO) metabolism.

A de novo 1.13 Mb microdeletion in 12q13.13 associated with congenital distal arthrogryposis, intellectual disability and mild dysmorphism.

A girl presented with congenital arthrogryposis, intellectual disability and mild bone-related dysmorphism. Molecular workup including the NimbleGen Human CGH 2.1M platform revealed a 1.

The distribution of a germline methylation marker suggests a regional mechanism of LINE-1 silencing by the piRNA-PIWI system.

Background: A defense system against transposon activity in the human germline based on PIWI proteins and piRNA has recently been discovered. It represses the activity of LINE-1 elements via DNA methylation by a largely unknown mechanism. Based on the dispersed distribution of clusters of piRNA genes in a strand-specific manner on all human chromosomes, we hypothesized that this system might work preferentially on local and proximal sequences.