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Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity. In this study, we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD, including de novo mutations, inherited variants, copy number variants (CNVs) and genomic structural variants. A higher mutation rate (Poisson test, P

Genetic alterations, together with environmental risk factors during infancy and childhood, contribute significantly to the etiology of autism spectrum disorder (ASD), a heterogeneous neurodevelopmental condition characterized by impairments in social interaction and restricted, repetitive behaviors. Mounting evidence points to a critical contribution of immunological risk factors to the development of ASD. By affecting multiple neurodevelopmental processes, immune system dysfunction could act as a point of convergence between genetics and environmental factors in ASD. Previous studies have shown altered cytokine levels in individuals with ASD, but research in Asian populations are limited. Here, we measured the plasma levels of 11 candidate cytokines in ASD and typically developing (TD) children. The cohort included 41 TD children and 87 children with ASD, aged 1-6 years. We found that as compared to the TD group, children with ASD had higher plasma levels of Eotaxin, TGF-β1 and TNF-α. The increase in TGF-β1 level was most significant in males, while the increase in Eotaxin was most significant in females. Eotaxin level negatively correlated with the social affect score (SA) in ADOS, while TNF-α level positively correlated with total development quotient (DQ), measured using GMDS. These pilot findings suggest potentially important roles of Eotaxin, TGF-β1 and TNF-α in ASD in the Chinese population. Autism Res 2018, 11: 989-999. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. Lay summary Alteration of immune system function is an important risk factor for autism spectrum disorder (ASD). Here we found that the levels of cytokines, including Eotaxin, TGF-β1 and TNF-α, are elevated in Chinese children with ASD, as compared to typically developing children. The change in TGF-β1 level was most prominent in boys, while that of Eotaxin was more significant in girls. These results provide evidence for changes in cytokine profile in Chinese children with ASD.

This study aims to explore prevalence and dissemination of antibiotic resistance genes (ARGs) in dairy farms. A variety of ARGs conferring resistance to most classes of antibiotics were detected in feces and soil samples obtained from dairy farms, using a high-throughput metagenomic sequencing approach. The ARGs observed in the feces and the soil samples were significantly correlated (p

SHANK3 deficiency represents one of the most replicated monogenic risk factors for autism spectrum disorder (ASD) and SHANK3 caused ASD presents a unique opportunity to understand the underlying neuropathological mechanisms of ASD. In this study, genetic tests, comprehensive clinical and neurobehavioral evaluations, as well as multimodal structural MRI using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were conducted in SHANK3 group (N = 14 with SHANK3 defects), ASD controls (N = 26 with idiopathic ASD without SHANK3 defects) and typically developing (TD) controls (N = 32). Phenotypically, we reported several new features in Chinese SHANK3 deficient children including anteverted nares, sensory stimulation seeking, dental abnormalities and hematological problems. In SHANK3 group, VBM revealed decreased grey matter volumes mainly in dorsal striatum, amygdala, hippocampus and parahippocampal gyrus; TBSS demonstrated decreased fractional anisotropy in multiple tracts involving projection, association and commissural fibers, including middle cerebral peduncle, corpus callosum, superior longitudinal fasciculus, corona radiata, external and internal capsule, and posterior thalamic radiation, etc. We report that the disrupted striatum centered brain structures are associated with SHANK3 deficient children. Study of subjects with monogenic cause offer specific insights into the neuroimaging studies of ASD. The discovery may support a path for future functional connectivity studies to allow for more in-depth understandings of the abnormal neural circuits and the underlying neuropathological mechanisms for ASD.

Bisphenol A (BPA) is a commonly used endocrine-disrupting chemical used as a component of polycarbonates plastics that has potential adverse effects on human health. Exposure to BPA during development has been implicated in memory deficits, but the mechanism of action underlying the effect is not fully understood. In this study, we investigated the effect of maternal exposure to BPA on object recognition memory and the expressions of proteins important for memory, especially focusing on the ERK/CREB/BDNF pathway. Pregnant Sprague-Dawley female rats were orally treated with either vehicle or BPA (0.05, 0.5, 5 or 50 mg/kg BW/day) during days 9-20 of gestation. Male offspring were tested on postnatal day 21 with the object recognition task. Recognition memory was assessed using the object recognition index (index=the time spent exploring the novel object/(the time spent exploring the novel object+the time spent exploring the familiar object)). In the test session performed 90 min after the training session, BPA-exposed male offspring not only spent more time in exploring the familiar object at the highest dose than the control, but also displayed a significantly decreased the object recognition index at the doses of 0.5, 5 and 50 mg/kg BW/day. During the test session performed 24h after the training session, BPA-treated males did not change the time spent exploring the familiar object, but had a decreased object recognition index at 5 and 50 mg/kg BW/day, when compared to control group. These findings indicate that object recognition memory was susceptible to maternal BPA exposure. Western blot analysis of hippocampi from BPA-treated male offspring revealed a decrease in Akt, phospho-Akt, p44/42 MAPK and phospho-p44/42 MAPK protein levels, compared to controls. In addition, BPA significantly inhibited the levels of phosphorylation of CREB and BDNF in the hippocampus. Our results show that maternal BPA exposure may full impair object recognition memory, and that impairment may be related to a decrease in Akt activation and an inhibition of the ERK/CREB/BDNF pathway in the hippocampus. This study also adds new evidence that suggests BPA has an antagonistic effect on the action of estrogen in the brain.

Excessive fluoride in natural water ecosystem has been demonstrated to have adverse effects on reproductive system in humans and mammals, while the most vulnerable aquatic organisms were ignored. In this study, the effects of waterborne fluoride on growth performance, sex steroid hormone, histological structure, and the transcriptional profiles of sex steroid related genes were examined in both female and male zebrafish exposed to different concentrations of 0.79, 18.60, 36.83 mg L(-1) of fluoride for 30 and 60 d to investigate the effects of fluoride on reproductive system and the underlying toxic mechanisms caused by fluoride. The results showed that the body weight was remarkably decreased, the structure of ovary and testis were serious injured, and the T and E2 levels were significantly reduced in male zebrafish. The transcriptional profiles of steroidogenic related genes displayed phenomenal alterations, the expressions of pgr and cyp19a1a were significantly up-regulated, while the transcriptional levels of er, ar and hsd3β were decreased both in the ovary and testis, and hsd17β8 were down-regulated just in males. Taken together, these results demonstrated that fluoride could significantly inhibit the growth of zebrafish, and notably affect the reproductive system in both sex zebrafish by impairing the structure of ovary and testis, altering steroid hormone levels and steroidogenic genes expression related to the synthesis of sex hormones in zebrafish.

Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which genetics plays a key aetiological role. The gene encoding NAD(P)H steroid dehydrogenase-like protein (NSDHL) is expressed in developing cortical neurons and glia, and its mutation may result in intellectual disability or congenital hemidysplasia. Case presentation An 8-year-old boy presented with a 260-kb NSDHL-containing duplication at Xq28 (151,868,909 – 152,129,300) inherited from his mother. His clinical features included defects in social communication and interaction, restricted interests, attention deficit, impulsive behaviour, minor facial anomalies and serum free fatty acid abnormality. Conclusion This is the first report of an ASD patient with a related NSDHL-containing duplication at Xq28. Further studies and case reports are required for genetic research to demonstrate that duplication as well as mutation can cause neurodevelopmental diseases. Electronic supplementary material The online version of this article (10.1186/s12881-018-0705-7) contains supplementary material, which is available to authorized users.

Florfenicol is extensively used in livestock to prevent or cure bacterial infections. However, it is not known whether the administration of florfenicol has resulted in the emergence and dissemination of florfenicol resistance genes (FRGs, including fexA, fexB, cfr, optrA, floR and pexA) in microbial populations in surrounding farm environments. Here we collected soil samples for the detection of FRGs and the residue of florfenicol from six swine farms with the record of florfenicol usage. Quantitative polymerase chain reaction and metagenomic sequencing revealed a significantly higher relative abundance of FRGs in the soils adjacent to the three swine farms where florfenicol was heavily used compared with the other sites. Meanwhile, the detectable levels of florfenicol were also identified in soils from two of these three farms using ultra-performance liquid chromatography tandem mass spectrometry. It appears that amount of florfenicol used on swine farms and the spreading of soils with swine waste could promote the prevalence and abundance of FRGs, including the linezolid resistance genes cfr and optrA, in adjacent soils and agricultural application of swine manure with florfenicol may have caused a residual level of florfenicol in the soils.

Background The cell adhesion molecule L1-like (CHL1 or CALL) gene is located on chromosome 3p26.3, and it is highly expressed in the central and peripheral nervous systems. The protein encoded by this gene is a member of the L1 family of neural cell adhesion molecules, and it plays a role in nervous system development and synaptic plasticity. Moreover, studies of mice have revealed that CHL1 is a prime candidate gene for a dosage-sensitive autosomal form of mental retardation. To date, four patients with a microdeletion and two with a microduplication of 3p26.3 encompassing only the CHL1 gene have been reported in literature. Case presentation In the present study, we have described a 16-month-old boy with autism spectrum disorder (ASD), developmental delay and minor dysmorphic facial features. This is the first report of a duplication of 3p26.3 including only the CHL1 gene in an ASD patient, and this duplication is the smallest reported to date in this gene. We also reviewed CHL1 gene mutation cases and examined whether this gene has an important role in cognitive function. Conclusions We conclude that both CHL1 deletions and duplications are likely responsible for the patient’s impaired cognitive function, and CHL1 may be an intriguing ASD candidate gene.