Characterization of a Mixed Methanotrophic Culture Capable of Chloroethylene Degradation

A consortium of methanotrophs cultured from the St. Joseph's aquifer in Schoolcraft, MI, was found to exhibit similar methane consumption rates as pure cultures of methanotrophs. The methanotrophic consortium resides within a portion of the aquifer contaminated with a mixed waste plume of perchloroethylene (PCE) and its reductive dechlorination products from natural attenuation, trichloroethylene (TCE), cis-dichloroethylene (c-DCE), and vinyl chloride (VC). Oxidation kinetics for TCE, c-DCE, and VC were measured for the mixed methanotroph consortium and compared to reported rate parameters for degradation of these chloroethylene compounds by pure methanotrophic cultures. The results demonstrate that the kinetics of chloroethylene oxidation by the Schoolcraft methanotroph population mimic the degradation rates of pure methanotrophic cultures that primarily express particulate methane monooxygenase (pMMO). Molecular and biochemical analyses confirmed that sMMO was not being expressed by these cells. Rather, using competitive reverse transcriptionpolymerase chain reaction, pmoA, a gene encoding one of the polypeptides of the pMMO was found at a level of (1.57 ± 0.10) × 10–17 mol pmoA mRNA/g wet soil in soil slurries and (2.65 ± 0.43) × 10–17 mol pmoA mRNA/μl in groundwater. No expression of mmoX, a gene encoding one of the polypeptides of the sMMO, was detected.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63398/1/ees.2005.22.177.pd

Meta-analysis of genome-wide association studies of anxiety disorders.

Anxiety disorders (ADs), namely generalized AD, panic disorder and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based on clinical presentation, ADs likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based ADs, we applied two phenotypic approaches: (1) comparisons between categorical AD cases and supernormal controls, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65 × 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86 × 10(-9)). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of ADs.Molecular Psychiatry advance online publication, 12 January 2016; doi:10.1038/mp.2015.197

A genome-wide association study of total child psychiatric problems scores

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits.</p

A powerful phenotype for gene-finding studies derived from trajectory analyses of symptoms of anxiety and depression between age seven and 18

To investigate the utility of longitudinal data in genetic analyses of symptoms of anxiety and depression, we assessed individual differences between age 7 and 18 using growth mixture models, and investigated the genetic and non-genetic factors contributing to the trajectories. Mothers of 7,706 girl and 7,418 boy twins from the Netherlands Twin Register rated the anxious depression scale (SxAnxDep) of the Child Behavior Check List (CBCL) at age 7, 10, and 12 years. Two thousand seven hundred and six girl and 1,856 boy twins completed the Youth Self Report (YSR) at age 14, 16, and 18. While individual trajectories varied considerably, these differences were largely idiosyncratic and could not be grouped into separate latent classes with class-specific average growth curves. The intercept, which reflects the individuals' baseline level of SxAnxDep across time, explained 55–58% of the total phenotypic variance. The slope factor, which captures a common average trend over time, did not explain variance in the phenotype. This finding also underlines the high level of idiosyncrasy of trajectories that lack a common longitudinal structure. The analyses of twin data showed that the random intercept factor of SxAnxDep during childhood and during adolescence is considerably more heritable than the observations at any single age, namely between 60% and 84%. One explanation is that different factors contribute to the level of symptoms of anxiety and depression at any given time point, including temporary events and emotions. When considering baseline stability, these temporary influences average out, with the result of a more reliable and more heritable phenotype. © 2015 Wiley Periodicals, Inc

Epstein-Barr Virus Serology as a Potential Screening Marker for Nasopharyngeal Carcinoma among High-Risk Individuals from Multiplex Families in Taiwan

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an EBV associated cancer that is highly treatable when diagnosed early, with 5-year disease-free survival of ~90%. However, NPC is typically diagnosed at advanced stages, where disease-free survival is <50%. There is therefore a need for clinical tools to assist in early NPC detection, particularly in high-risk individuals. METHODS: We evaluated the ability of anti-EBV IgA antibodies to detect incident NPC among high-risk Taiwanese individuals. NPC cases (N=21) and age and sex-matched controls (N=84) were selected. Serum collected prior to NPC diagnosis was tested for ELISA-based IgA markers against the following EBV peptides: EBNA1, VCAp18, EAp138, Ead_p47, and VCAp18 + EBNA1 peptide mixture. The sensitivity, specificity, and screening program parameters were calculated. RESULTS: EBNA1 IgA had the best performance characteristics. At an optimized threshold value, EBNA1 IgA measured at baseline identified 80% of the high-risk individuals who developed NPC during follow-up (80% sensitivity). However, approximately 40% of high-risk individuals who did not develop NPC also tested positive (false positives). Application of EBNA1 IgA as a biomarker to detect incident NPC in a previously unscreened, high-risk population revealed that 164 individuals needed to be screened to detect 1 NPC and that 69 individuals tested positive per case detected. CONCLUSIONS: EBNA1 IgA proved to be a sensitive biomarker for identifying incident NPC, but future work is warranted to develop more specific screening tools to decrease the number of false positives. IMPACT: Results from this study could inform decisions regarding screening biomarkers and referral thresholds for future NPC early-detection program evaluations

Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis

BACKGROUND: Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia. METHODS: We analysed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33,332 cases and 27,888 controls of European ancestory. To characterise allelic effects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fitting model of relations between genotype and phenotype. We examined cross-disorder effects of genome-wide significant loci previously identified for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such effects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the five disorders. We used enrichment analysis of expression quantitative trait loci (eQTL) data to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples. FINDINGS: SNPs at four loci surpassed the cutoff for genome-wide significance (p<5×10(-8)) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2. Model selection analysis supported effects of these loci for several disorders. Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specificity. Polygenic risk scores showed cross-disorder associations, notably between adult-onset disorders. Pathway analysis supported a role for calcium channel signalling genes for all five disorders. Finally, SNPs with evidence of cross-disorder association were enriched for brain eQTL markers. INTERPRETATION: Our findings show that specific SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic effects on psychopathology. These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause. FUNDING: National Institute of Mental Health