The Mutationathon highlights the importance of reaching standardization in estimates of pedigree-based germline mutation rates

In the past decade, several studies have estimated the human per-generation germline mutation rate using large pedigrees. More recently, estimates for various nonhuman species have been published. However, methodological differences among studies in detecting germline mutations and estimating mutation rates make direct comparisons difficult. Here, we describe the many different steps involved in estimating pedigree-based mutation rates, including sampling, sequencing, mapping, variant calling, filtering, and appropriately accounting for false-positive and false-negative rates. For each step, we review the different methods and parameter choices that have been used in the recent literature. Additionally, we present the results from a \u27Mutationathon,\u27 a competition organized among five research labs to compare germline mutation rate estimates for a single pedigree of rhesus macaques. We report almost a twofold variation in the final estimated rate among groups using different post-alignment processing, calling, and filtering criteria, and provide details into the sources of variation across studies. Though the difference among estimates is not statistically significant, this discrepancy emphasizes the need for standardized methods in mutation rate estimations and the difficulty in comparing rates from different studies. Finally, this work aims to provide guidelines for computational and statistical benchmarks for future studies interested in identifying germline mutations from pedigrees

Single-cell epigenomics reveals mechanisms of human cortical development

During mammalian development, differences in chromatin state coincide with cellular differentiation and reflect changes in the gene regulatory landscap

Preliminary Assessment of Microbial Community Structure of Wind-Tidal Flats in the Laguna Madre, Texas, USA

Aside from two samples collected nearly 50 years ago, little is known about the microbial composition of wind tidal flats in the hypersaline Laguna Madre, Texas. These mats account for ~42% of the lagoon’s area. These microbial communities were sampled at four locations that historically had mats in the Laguna Madre, including Laguna Madre Field Station (LMFS), Nighthawk Bay (NH), and two locations in Kenedy Ranch (KRN and KRS). Amplicon sequencing of 16S genes determined the presence of 51 prokaryotic phyla dominated by Bacteroidota, Chloroflexi, Cyanobacteria, Desulfobacteria, Firmicutes, Halobacteria, and Proteobacteria. The microbial community structure of NH and KR is significantly different to LMFS, in which Bacteroidota and Proteobacteria were most abundant. Twenty-three cyanobacterial taxa were identified via genomic analysis, whereas 45 cyanobacterial taxa were identified using morphological analysis, containing large filamentous forms on the surface, and smaller, motile filamentous and coccoid forms in subsurface mat layers. Sample sites were dominated by species in Oscillatoriaceae (i.e., Lyngbya) and Coleofasciculaceae (i.e., Coleofasciculus). Most cyanobacterial sequences (~35%) could not be assigned to any established taxa at the family/genus level, given the limited knowledge of hypersaline cyanobacteria. A total of 73 cyanobacterial bioactive metabolites were identified using ultra performance liquid chromatography-Orbitrap MS analysis from these commu nities. Laguna Madre seems unique compared to other sabkhas in terms of its microbiolog

Gravitational Wave Memory of Gamma-Ray Burst Jets

Gamma-Ray Bursts (GRBs) are now considered as relativistic jets. We analyze the gravitational waves from the acceleration stage of the GRB jets. We show that (i) the point mass approximation is not appropriate if the opening half-angle of the jet is larger than the inverse of the Lorentz factor of the jet, (ii) the gravitational waveform has many step function like jumps, and (iii) the practical DECIGO and BBO may detect such an event if the GRBs occur in Local group of galaxy. We found that the light curve of GRBs and the gravitational waveform are anti-correlated so that the detection of the gravitational wave is indispensable to determine the structure of GRB jets.Comment: Revtex4, 10 pages, 6 figures, Fig.2 and Fig.3 replaced, minor changes to text in Sec.I and Sec.V, typos corrected, some reference added, Version to be published in PR

Coding and noncoding variants in EBF3 are involved in HADDS and simplex autism

BACKGROUND: Previous research in autism and other neurodevelopmental disorders (NDDs) has indicated an important contribution of protein-coding (coding) de novo variants (DNVs) within specific genes. The role of de novo noncoding variation has been observable as a general increase in genetic burden but has yet to be resolved to individual functional elements. In this study, we assessed whole-genome sequencing data in 2671 families with autism (discovery cohort of 516 families, replication cohort of 2155 families). We focused on DNVs in enhancers with characterized in vivo activity in the brain and identified an excess of DNVs in an enhancer named hs737. RESULTS: We adapted the fitDNM statistical model to work in noncoding regions and tested enhancers for excess of DNVs in families with autism. We found only one enhancer (hs737) with nominal significance in the discovery (p = 0.0172), replication (p = 2.5 × 10 CONCLUSIONS: In this study, we identify DNVs in the hs737 enhancer in individuals with autism. Through multiple approaches, we find hs737 targets the gene EBF3 that is genome-wide significant in NDDs. By assessment of noncoding variation and the genes they affect, we are beginning to understand their impact on gene regulatory networks in NDDs

Applying shari'a in the West : facts, fears and the future of Islamic rules on family relations in the West

This volume provides new insights in the concept of shari’a in the West, and sets out a framework of how shari’a in the West can be studied. The premise of this volume is that one needs to focus on the question ‘What do Muslims do in terms of shari’a?’ rather than ‘What is shari’a?’. This perspective shows that the practice of Sharia is restricted to a limited set of rules that mainly relate to religious rituals, family law and social interaction. The framework of this volume then continues to explore two more interactions: the Western responses to these practices of shari’a and, in turn, the Muslim legal reaction to these responses.9789400601055 (pdf); 9789400601062 (epub)Wetensch. publicati