REPORT Whole-Exome Sequencing Links a Variant in DHDDS to Retinitis Pigmentosa

Increasingly, mutations in genes causing Mendelian disease will be supported by individual and small families only; however, exome sequencing studies have thus far focused on syndromic phenotypes characterized by low locus heterogeneity. In contrast, retinitis pigmentosa (RP) is caused by >50 known genes, which still explain only half of the clinical cases. In a single, one-generation, nonsyndromic RP family, we have identified a gene, dehydrodolichol diphosphate synthase (DHDDS), demonstrating the power of combining whole-exome sequencing with rapid in vivo studies. DHDDS is a highly conserved essential enzyme for dolichol synthesis, permitting global N-linked glycosylation. Zebrafish studies showed virtually identical photoreceptor defects as observed with N-linked glycosylation-interfering mutations in the light-sensing protein rhodopsin. The identified Lys42Glu variant likely arose from an ancestral founder, because eight of the nine identified alleles in 27,174 control chromosomes were of confirmed Ashkenazi Jewish ethnicity. These findings demonstrate the power of exome sequencing linked to functional studies when faced with challenging study designs and, importantly, link RP to the pathways of N-linked glycosylation, which promise new avenues for therapeutic interventions. Retinitis pigmentosa (RP) refers to a large group of genetically heterogeneous retinal degenerative disorders characterized by early rod photoreceptor dysfunction followed by progressive rod and cone photoreceptor dysfunction and photoreceptor death (MIM 268000). Impaired night vision followed by impaired peripheral vision generally starts in adolescence to young adulthood, with subsequent impaired central vision in later life. We studied a family of Ashkenazi Jewish (AJ) origin in which three out of four siblings (two females and one male) were diagnosed with RP in their teenage years ( To identify the genetic cause of this likely recessive subtype of RP, we screened all genes known to harbor RP mutations and found that they were negative for mutations. Classic linkage approaches were not applicable because of the size of the nonconsanguineous family, so we performed whole-exome sequencing in the three affected siblings and one unaffected sibling (Whole Human Exome Capture kit, Roche). We produced approximately 10 gigabases (Gb) of paired-end 75 bp sequence reads per individual on the Illumina GAII platform. To test the overall quality of the sequence data, we compared the genotypes of variants found in the sequence data to variants derived from genotyping via a genome-wide SN

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Characterization and sorption ability of wool powder

This work focused on the characterisation of wool powders and their sorption capacity for dyes and metal ions. It provides new information to the field of wool and the potential use of wool to sorb contaminants from wastewater. It also suggests a new use for inferior and waste wool

Effect of Boric Acid on the Ionization Equilibrium of α-Hydroxy Carboxylic Acids and the Study of Its Applications

To investigate the synergistic catalytic effects of boric acid and α-hydroxycarboxylic acids (HCAs), we analyzed and measured the effects of the complexation reactions between boric acid and HCAs on the ionization equilibrium of the HCAs. Eight HCAs, glycolic acid, D-(−)-lactic acid, (R)-(−)-mandelic acid, D-gluconic acid, L-(−)-malic acid, L-(+)-tartaric acid, D-(−)-tartaric acid, and citric acid, were selected to measure the pH changes in aqueous HCA solutions after adding boric acid. The results showed that the pH values of the aqueous HCA solutions gradually decreased with an increase in the boric acid molar ratio, and the acidity coefficients when boric acid formed double-ligand complexes with HCAs were smaller than those of the single-ligand complexes. The more hydroxyl groups the HCA contained, the more types of complexes could be formed, and the greater the rate of change in the pH. The total rates of change in the pH of the HCA solutions were in the following order: citric acid > L-(−)-tartaric acid = D-(−)-tartaric acid > D-gluconic acid > (R)-(−)-mandelic acid > L-(−)-malic acid > D-(−)-lactic acid > glycolic acid. The composite catalyst of boric acid and tartaric acid had a high catalytic activity—the yield of methyl palmitate was 98%. After the reaction, the catalyst and methanol could be separated by standing stratification

Resonance Rayleigh Scattering and SERS Spectral Detection of Trace Hg(II) Based on the Gold Nanocatalysis

Mercury (Hg) is a heavy metal pollutant, there is an urgent need to develop simple and sensitive methods for Hg(II) in water. In this article, a simple and sensitive resonance Rayleigh scattering (RRS) method was developed for determination of 0.008–1.33 µmol/L Hg, with a detection limit of 0.003 μmol/L, based on the Hg(II) regulation of gold nanoenzyme catalysis on the HAuCl4-H2O2 to form gold nanoparticles (AuNPs) with an RRS peak at 370 nm. Upon addition of molecular probes of Victoria blue B (VBB), the surface-enhanced Raman scattering (SERS) peak linearly decreased at 1612 cm−1 with the Hg(II) concentration increasing in the range of 0.013–0.5 μmol/L. With its good selectivity and good accuracy, the RRS method is expected to be a promising candidate for determining mercury ions in water samples

A Dimode Scattering Method for Ultratrace Dinitrofuran Detection with Nanopalladium Molecularly Imprinted Polymer Nanocatalytic Probe

With four nanoparticles as the nanomatrix, dinotefuran (DNF) as the template molecule, N-isopropylacrylamide as the functional monomer, trimethylolpropane and trimethacrylate as the cross-linker, four nanosurface molecularly imprinted polymer (MIP) bifunctional probes were prepared by microwave synthesis. It was found that palladium nanosurface MIP (Pd@MIP) not only recognized DNF but also had the strongest catalytic effect on the new nanogold indicator reaction of acrylic acid-HAuCl4, which was evaluated quickly with the slope procedure developed by us. The generated gold nanoparticles (AuNPs) not only possessed the resonance Rayleigh scattering (RRS) effect but also strong surface-enhanced Raman scattering (SERS) activity. The combination of Pd@MIP with DNF enhanced the catalytic effect by coupling the nanosurface electrons with π-electrons, thus enhancing both scattering signals. A new Pd@MIP nanoprobe catalytic-SERS/RRS dual-mode analytical platform was developed for the specific and sensitive detection of DNF. The linear ranges of the SERS and RRS methods were 0.075–0.75 and 0.1–0.75 nmol/L, and the limits of detection were 0.03 and 0.06 nmol/L, respectively. The standard deviations were 0.54–2.39%, and the recoveries were 93–105%

A Highly Sensitive SERS and RRS Coupled Di-Mode Method for CO Detection Using Nanogolds as Catalysts and Bifunctional Probes

Carbon monoxide (CO) is a commonly poisonous gas. It is important to detect CO in daily life. Herein, a new and sensitive surface enhanced Raman scattering (SERS) and resonance Rayleigh scattering (RRS) coupled di-mode method was developed for CO, based on gold nano-enzyme catalysis and gold nanoprobes. CO can react with HAuCl4 to generate gold nanoparticles (AuNPs) in pH 5.2 HAc-NaAc buffer. The generated AuNPs exhibited SERS activity at 1620 cm−1 in the presence of Vitoria blue B (VBB) molecular probes, and an RRS peak at 290 nm. Based on the AuNP bifunctional probes, the increased SERS and RRS intensities respond linearly with the concentration of CO in the range of 100–1500 ng/mL and 30–5230 ng/mL, respectively. To improve the sensitivity, the produced AuNPs were used as nano-enzyme catalysts for the new indicator reaction of HAuCl4-ethanol (En) to amplify the signal. The sensitive SERS method was coupled with the accurate RRS method to develop a sensitive and accurate SERS/RRS di-mode method for determination of 3.0–413 ng/mL CO, based on the AuNP-HAuCl4-En nanocatalytic reaction and its product of AuNPs as SERS and RRS bifunctional probes

Wool powders used as sorbents to remove Co2+ ions from aqueous solution

The Co2+ sorption of two wool powders was investigated using its radioisotope 57Co (T1/2=271.8 days and &gamma;=122.1 and 136.5 keV) as a tracer. The effects of the type of buffer, the pH value, the contact time and the initial concentration of Co2+ on the sorption behaviour of wool powders were studied. The Co2+ releasing ability of wool powders and the re-use of wool powders to sorb Co2+ were also examined. The optimum sorption of Co2+ by the powders occurred at pH 8 in phosphate buffer and pH 10 in ammonium sulphate buffer. Fourier-transform infrared spectroscopy (FTIR) was used to study the changes in chemical structure of the wool after exposure to both buffer solutions. Compared to the untreated wool fibre, the fine wool powders showed rapid sorption rates and high sorption capacities for Co2+. Co2+ ions were recovered after exposing the Co2+ loaded wool to HCl (0.1 M) and buffer at pH 3 (glycine/sodium chloride). After releasing Co2+ ions from wool powders, the efficiency of wool powders re-used to sorb Co2+ was 80% of that of the fresh wool powders. It is concluded from this study that wool powder can be used as an efficient sorbent to remove and release Co2+ from solution.<br /