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

The Presence of Donor-Specific Antibodies in Renal Transplantation

Determining the presence of anti-HLA antibodies before transplantation is an important factor to prevent loss of function among renal transplantations. In addition, recent studies have shown that not only the pretransplantation existence of anti-HLA antibody but also posttransplantation donor-specific antibodies (DSA) and non-donor-specific antibodies are significantly associated with allograft rejection or loss of graft function. This study presented DSA among patients after renal transplantation together with graft function and survival

Is Flow Cytometry Crossmatch Analysis Using Sera with Different Dilutions Important for Pretransplant Analysis? A Case Report

The most effective form of treatment for chronic renal failure is kidney transplantation from a cadaver or a living donor. For a kidney transplant to be successful, tissue compatibility and a lack of donor-specific anti-human leukocyte antigen (H LA) antibodies in the circulation of the patient are vital, in addition to ABO blood group compatibility. The presence of anti-HLA antibodies. is assayed before transplantation using various methods, but because organ rejections have been observed in previous studies, different techniques are required to detect anti-FILA antibodies. Today, flow cytometry crossmatching is one of the most important and effective techniques in testing for donor-specific anti-HLA antibodies (DSAs). If weakly positive serum is assayed after serial dilution, it can yield high positivity. Herein, we describe the differences between the results for diluted and undiluted weakly positive sera studied using the flow cytometry crossmatch (FCXM) technique. In a recent study, the sera of weakly FCXM-positive patients were diluted 1/50, and the FCXM test was repeated. The use of diluted serum eliminated the effect of the prozone so that the DSAs could be detected

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)

Comparison of the essential oils of Prangos turcica A. Duran, M. Sagiroglu et H. Duman fruits obtained by different isolation techniques

Baser, K. Husnu Can/0000-0003-2710-0231; Ozek, Temel/0000-0003-4251-8783WOS: 000240698400013The essential oils from fruits of Prangos turcica A. Duran, M. Sagiroglu et H. Duman were obtained by hydrodistillation (HD), microdistillation (MD), micro-steam distilled solid-phase microextraction (MSD-SPME) techniques and then analyzed by GC and GC/MS methods. The oils showed similar composition with some quantitative differences. The main components of the oils were found to be alpha-humulene, germacrene D, naphthalene, terpinolene, p-cymene, gamma-elemene and bornyl acetate

A further family of Stromme syndrome carrying CENPF mutation.

Stromme syndrome is a rare genetic disorder characterized by microcephaly, anterior ocular chamber anomalies, and "apple peel" type jejunal atresia. Here, we report a Stromme syndrome family with two affected siblings with a homozygous truncating frameshift mutation in CENPF. A 3-month-old girl was hospitalized due to prenatally diagnosed microcephaly, microphthalmia, and dysmorphological features. The history of a previous child with the same findings in addition to "apple peel" intestinal atresia had been noted. Regarding the clinical features of both affected siblings, a diagnosis of Stromme syndrome was established. Exome-sequencing of these two cases showed the homozygous mutation (c.5912_5913insA)/(p.T1974Nfs*9) in CENPF. While confirmation of this gene being responsible for Stromme syndrome was pending our results, Filges et al. reported that CENPF was indeed underlying the reason for Stromme syndrome. This is the second case report identifying CENPF mutation as the cause of Stromme syndrome

A further family of Stromme syndrome carrying CENPF mutation

Stromme syndrome is a rare genetic disorder characterized by microcephaly, anterior ocular chamber anomalies, and “apple peel” type jejunal atresia. Here, we report a Stromme syndrome family with two affected siblings with a homozygous truncating frameshift mutation in CENPF. A 3-month-old girl was hospitalized due to prenatally diagnosed microcephaly, microphthalmia, and dysmorphological features. The history of a previous child with the same findings in addition to “apple peel” intestinal atresia had been noted. Regarding the clinical features of both affected siblings, a diagnosis of Stromme syndrome was established. Exome-sequencing of these two cases showed the homozygous mutation (c.5912_5913insA)/(p.T1974Nfs*9) in CENPF. While confirmation of this gene being responsible for Stromme syndrome was pending our results, Filges et al. reported that CENPF was indeed underlying the reason for Stromme syndrome. This is the second case report identifying CENPF mutation as the cause of Stromme syndrome. © 2017 Wiley Periodicals, Inc