Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

We systematically analyzed postzygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous PZMs within critical exons of prenatally expressed genes were more common in ASD probands than controls (P < 1 Ã 10-6), and genes carrying these PZMs were enriched for expression in the amygdala (P = 5.4 Ã 10-3). Two genes (KLF16 and MSANTD2) were significantly enriched for PZMs genome-wide, and other PZMs involved genes (SCN2A, HNRNPU and SMARCA4) whose mutation is known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk

The Androchair : Performing Gynaecology through the Practice of Gender Critical Design

This paper highlights the important role that design plays when it comes to women’s overall experi- ences of ther gynaecological examination. It exempli es how the examination can become renegotiable through the practice of a critical design. We will re ect this in the design of the contemporary gynaecological examination chair (GEC). We used women’s experiences as a starting point for the design of an Androchair (a conceptual male equivalent of the GEC), in order to make the experiences critically visible. Inspired by the view of the gynaecolog- ical examination as a performance where the Androchair is represented as a prop and was placed on a stage as a discussion object during a public seminar. The Androchair allowed for both critical and multiple readings of the GEC and through that, the gynaecology examination at large. Moreover, it stimulated a discussion about alternative ideas towards achieving a more positive experience. QC 20170224</p

Episignatures Stratifying Helsmoortel-Van Der Aa Syndrome Show Modest Correlation with Phenotype

Helsmoortel-Van der Aa syndrome (HVDAS) is a neurodevelopmental condition associated with intellectual disability/developmental delay, autism spectrum disorder, and multiple medical comorbidities. HVDAS is caused by mutations in activity-dependent neuroprotective protein (ADNP). A recent study identified genome-wide DNA methylation changes in 22 individuals with HVDAS, adding to the group of neurodevelopmental disorders with an epigenetic signature. This methylation signature segregated those with HVDAS into two groups based on the location of the mutations. Here, we conducted an independent study on 24 individuals with HVDAS and replicated the existence of the two mutation-dependent episignatures. To probe whether the two distinct episignatures correlate with clinical outcomes, we used deep behavioral and neurobiological data from two prospective cohorts of individuals with a genetic diagnosis of HVDAS. We found limited phenotypic differences between the two HVDAS-affected groups and no evidence that individuals with more widespread methylation changes are more severely affected. Moreover, in spite of the methylation changes, we observed no profound alterations in the blood transcriptome of individuals with HVDAS. Our data warrant caution in harnessing methylation signatures in HVDAS as a tool for clinical stratification, at least with regard to behavioral phenotypes

Regional and sociodemographic differences in average BMI among US children in the ECHO program

OBJECTIVE: The aim of this study was to describe the association of individual-level characteristics (sex, race/ethnicity, birth weight, maternal education) with child BMI within each US Census region and variation in child BMI by region. METHODS: This study used pooled data from 25 prospective cohort studies. Region of residence (Northeast, Midwest, South, West) was based on residential zip codes. Age- and sex-specific BMI z scores were the outcome. RESULTS: The final sample included 14,313 children with 85,428 BMI measurements, 49% female and 51% non-Hispanic White. Males had a lower average BMI z score compared with females in the Midwest (β = -0.12, 95% CI: -0.19 to -0.05) and West (β = -0.12, 95% CI: -0.20 to -0.04). Compared with non-Hispanic White children, BMI z score was generally higher among children who were Hispanic and Black but not across all regions. Compared with the Northeast, average BMI z score was significantly higher in the Midwest (β = 0.09, 95% CI: 0.05-0.14) and lower in the South (β = -0.12, 95% CI: -0.16 to -0.08) and West (β = -0.14, 95% CI: -0.19 to -0.09) after adjustment for age, sex, race/ethnicity, and birth weight. CONCLUSIONS: Region of residence was associated with child BMI z scores, even after adjustment for sociodemographic characteristics. Understanding regional influences can inform targeted efforts to mitigate BMI-related disparities among children

Maternal tobacco smoking and offspring autism spectrum disorder or traits in ECHO cohorts

Given inconsistent evidence on preconception or prenatal tobacco use and offspring autism spectrum disorder (ASD), this study assessed associations of maternal smoking with ASD and ASD-related traits. Among 72 cohorts in the Environmental Influences on Child Health Outcomes consortium, 11 had ASD diagnosis and prenatal tobaccosmoking (n&nbsp;=&nbsp;8648). and 7 had Social Responsiveness Scale (SRS) scores of ASD traits (n&nbsp;=&nbsp;2399). Cohorts had diagnoses alone (6), traits alone (2), or both (5). Diagnoses drew from parent/caregiver report, review of records, or standardized instruments. Regression models estimated smoking-related odds ratios (ORs) for diagnoses and standardized mean differences for SRS scores. Cohort-specific ORs were meta-analyzed. Overall, maternal smoking was unassociated with child ASD (adjusted OR, 1.08; 95% confidence interval [CI], 0.72-1.61). However, heterogeneity across studies was strong: preterm cohorts showed reduced ASD risk for exposed children. After excluding preterm cohorts (biased by restrictions on causal intermediate and exposure opportunity) and small cohorts (very few ASD cases in either smoking category), the adjusted OR for ASD from maternal smoking was 1.44 (95% CI, 1.02-2.03). Children of smoking (versus non-smoking) mothers had more ASD traits (SRS T-score + 2.37 points, 95% CI, 0.73-4.01 points), with results homogeneous across cohorts. Maternal preconception/prenatal smoking was consistently associated with quantitative ASD traits and modestly associated with ASD diagnosis among sufficiently powered United States cohorts of non-preterm children. Limitations resulting from self-reported smoking and unmeasured confounders preclude definitive conclusions. Nevertheless, counseling on potential and known risks to the child from maternal smoking is warranted for pregnant women and pregnancy planners. LAY SUMMARY: Evidence on the association between maternal prenatal smoking and the child's risk for autism spectrum disorder has been conflicting, with some studies reporting harmful effects, and others finding reduced risks. Our analysis of children in the ECHO consortium found that maternal prenatal tobacco smoking is consistently associated with an increase in autism-related symptoms in the general population and modestly associated with elevated risk for a diagnosis of autism spectrum disorder when looking at a combined analysis from multiple studies that each included both pre- and full-term births. However, this study is not proof of a causal connection. Future studies to clarify the role of smoking in autism-like behaviors or autism diagnoses should collect more reliable data on smoking and measure other exposures or lifestyle factors that might have confounded our results

Regional and sociodemographic differences in average BMI among US children in the ECHO program

ObjectiveThe aim of this study was to describe the association of individual-level characteristics (sex, race/ethnicity, birth weight, maternal education) with child BMI within each US Census region and variation in child BMI by region.MethodsThis study used pooled data from 25 prospective cohort studies. Region of residence (Northeast, Midwest, South, West) was based on residential zip codes. Age- and sex-specific BMI z scores were the outcome.ResultsThe final sample included 14,313 children with 85,428 BMI measurements, 49% female and 51% non-Hispanic White. Males had a lower average BMI z score compared with females in the Midwest (β&nbsp;=&nbsp;-0.12, 95% CI: -0.19 to -0.05) and West (β&nbsp;=&nbsp;-0.12, 95% CI: -0.20 to -0.04). Compared with non-Hispanic White children, BMI z score was generally higher among children who were Hispanic and Black but not across all regions. Compared with the Northeast, average BMI z score was significantly higher in the Midwest (β&nbsp;=&nbsp;0.09, 95% CI: 0.05 to 0.14) and lower in the South (β&nbsp;=&nbsp;-0.12, 95% CI: -0.16 to -0.08) and West (β&nbsp;=&nbsp;-0.14, 95% CI: -0.19 to -0.09) after adjustment for age, sex, race/ethnicity, and birth weight.ConclusionsRegion of residence was associated with child BMI z scores, even after adjustment for sociodemographic characteristics. Understanding regional influences can inform targeted efforts to mitigate BMI-related disparities among children

2015 Atomic Spectrometry Update – a review of advances in X-ray fluorescence spectrometry and their applications

This review describes advances in the X-ray fluorescence (XRF) group of techniques published approximately between April 2014 and March 2015 and is therefore restricted to a selection of papers featuring developments in the XRF armoury. An active topic during this review period was that of imaging techniques and, more particularly of micro XRF spectrometry. Silicon-based semiconductor X-ray detectors such as SDD and Si(PIN) continue to reflect the maturity and widespread routine use of such devices. The significant expansion in studies evaluating the field use of portable XRF instrumentation in geological applications, often still proving the quality of the data, rather than adopting the technique in routine applications. New synchrotron beamlines offer previously unavailable spatial resolution and throughput for the characterisation of advanced energy materials and devices under varying temperatures and gas atmospheres. Nanomaterials feature extensively this year such as the use of nanoparticles in cancer imaging and therapy. Synchrotron radiation has become a preferred technique for the analysis of a wide range of archeological samples, artwork, museum specimens and environmental studies. There has been a substantial rise in the number of Chinese researchers investigating objects of cultural heritage, especially porcelain, glazes and glass. Advances in TXRF and related techniques continue to feature with studies on thin films and nanomaterials. Feedback on this review is most welcome and the review coordinator can be contacted using the email address provided

Enabling the genomic revolution in Africa

H3Africa is developing capacity for health-related genomics research in Afric