Early postzygotic mutations contribute to de novo variation in a healthy monozygotic twin pair

Cataloged from PDF version of article.Background: Human de novo single-nucleotide variation (SNV) rate is estimated to range between 0.82-1.70×10-8 mutations per base per generation. However, contribution of early postzygotic mutations to the overall human de novo SNV rate is unknown. Methods: We performed deep whole-genome sequencing (more than 30-fold coverage per individual) of the whole-blood-derived DNA samples of a healthy monozygotic twin pair and their parents. We examined the genotypes of each individual simultaneously for each of the SNVs and discovered de novo SNVs regarding the timing of mutagenesis. Putative de novo SNVs were validated using Sanger-based capillary sequencing. Results: We conservatively characterised 23 de novo SNVs shared by the twin pair, 8 de novo SNVs specific to twin I and 1 de novo SNV specific to twin II. Based on the number of de novo SNVs validated by Sanger sequencing and the number of callable bases of each twin, we calculated the overall de novo SNV rate of 1.31×10-8 and 1.01×10-8 for twin I and twin II, respectively. Of these, rates of the early postzygotic de novo SNVs were estimated to be 0.34×10-8 for twin I and 0.04×10-8 for twin II. Conclusions: Early postzygotic mutations constitute a substantial proportion of de novo mutations in humans. Therefore, genome mosaicism resulting from early mitotic events during embryogenesis is common and could substantially contribute to the development of diseases

A Survey of Bayesian Statistical Approaches for Big Data

The modern era is characterised as an era of information or Big Data. This has motivated a huge literature on new methods for extracting information and insights from these data. A natural question is how these approaches differ from those that were available prior to the advent of Big Data. We present a review of published studies that present Bayesian statistical approaches specifically for Big Data and discuss the reported and perceived benefits of these approaches. We conclude by addressing the question of whether focusing only on improving computational algorithms and infrastructure will be enough to face the challenges of Big Data

The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

Frequency of audiological complaints in patients with fibromyalgia syndrome and its relationship with oxidative stress

Aim: Central sensitization‑related neuroaudiological symptoms are frequently seen in patients with fibromyalgia syndrome (FMS). This study aimed to evaluate the audiological signs and symptoms in patients with FMS and explore their relationship with oxidative stress markers.Methods: This prospective controlled cross‑sectional study compared the serum myeloperoxidase, superoxide dismutase, glutathione peroxidase (GPx), nitric oxide (NO), and malondialdehyde (MDA) concentrations in 44 patients with FMS diagnosed according to the 2010 American College of Rheumatology criteria and 44healthy volunteers. FMS severity was assessed using the visual analog scale and Fibromyalgia Impact Questionnaire. An audiological assessment including vocalizations, vertigo, balance problems, and hearing problems was done to all participants.Results: The two groups were of similar age (P = 0.24), gender (P = 0.40), and weight distribution (P = 0.6). Vertigo, tinnitus, hearing, and balance complaints (P = 0.01/P = 0.00/P = 0.00/P = 0.01) were significantly higher in the FMS group. All subunits and total scores of dizziness handicap inventory were significantly higher (P = 0.00/P = 0.00/P = 0.01/P = 0.01) in the FMS group. An antioxidant GPx and oxidant parameters such as NO and MDA were found to be significantly higher (P = 0.00/P = 0.01/P = 0.02). The hearing assessments at frequencies between 250 and 12,000 Hz showed a significant difference between the two groups (high hearing frequencies in the FMS group) in audiometry. No significant difference was found between the two groups in terms of the presence of stabilo‑acoustic reflex, intraaural pressure, and compliance (P = 0.18/P = 0.33/P = 0.41) in tympanogram.Conclusions: Patients with FMS have high levels of oxidative stress markers (GPx, NO, and MDA), highly frequent audiological symptoms with high hearing frequencies in audiometry, independent of disease severity.Keywords: Audiologic disorders, fibromyalgia, oxidative stres

In vitro and in vivo Performance of Polyethyleneimine (PEI) Brushes Integrated on Polyurethane (PU) Ureteral Stents Against Biofilm Formation and Encrustation

4th TERMIS World Congress -- SEP 08-11, 2015 -- Boston, MAWOS: 000360205200068…TERMI

Flow Cytometric Evaluation of Pregnancy-Induced Anti-Donor Immunization

Background. Living donor kidneys from spouses and children (from offspring to parents) are currently considered to be important organ sources. However, pregnancy-induced alloimmunization may provoke acute rejection episodes after kidney transplantation, being flow cytometry cross-match (FCXM) we studied donor-specific antibodies (DSAs) in the sera of recipients planned for living kidney transplantation from their spouse or children. When the FCXM was positive, we confirmed the existence of anti-human leukocyte antigen (H LA) antibodies using flow cytometry panel-reactive antibody (flow-PRA)