A five-gene molecular phylogeny reveals Parapanteles Ashmead (Hymenoptera: Braconidae) to be polyphyletic as currently composed.

Parapanteles Ashmead (Braconidae: Microgastrinae) is a medium-sized genus of microgastrine wasps that was erected over a century ago and lacks a unique synapomorphic character, and its monophyly has not been tested by any means. Parapanteles usually are parasitoids of large, unconcealed caterpillars (macrolepidoptera) and have been reared from an unusually large diversity of hosts for a relatively small microgastrine genus. We used Cytochrome Oxidase I sequences ("DNA barcodes") available for Parapanteles and other microgastrines to sample the generic diversity of described and undescribed species currently placed in Parapanteles, and then sequenced four additional genes for this subsample (wingless, elongation factor 1-alpha, ribosomal subunit 28s, and NADH dehydrogenase subunit 1). We constructed individual gene trees and concatenated Bayesian and maximum-likelihood phylogenies for this 5-gene subsample. In these phylogenies, most Parapanteles species formed a monophyletic clade within another genus, Dolichogenidea, while the remaining Parapanteles species were recovered polyphyletically within several other genera. The latter likely represent misidentified members of other morphologically similar genera. Species in the monophyletic clade containing most Parapanteles parasitized caterpillars from only five families - Erebidae (Arctiinae), Geometridae, Saturniidae, Notodontidae, and Crambidae. We do not make any formal taxonomic decisions here because we were not able to include representatives of type species for Parapanteles or other relevant genera, and because we feel such decisions should be reserved until a comprehensive morphological analysis of the boundaries of these genera is accomplished.

Genome-wide association study identifies a novel locus for cannabis dependence.

Despite moderate heritability, only one study has identified genome-wide significant loci for cannabis-related phenotypes. We conducted meta-analyses of genome-wide association study data on 2080 cannabis-dependent cases and 6435 cannabis-exposed controls of European descent. A cluster of correlated single-nucleotide polymorphisms (SNPs) in a novel region on chromosome 10 was genome-wide significant (lowest P=1.3E-8). Among the SNPs, rs1409568 showed enrichment for H3K4me1 and H3K427ac marks, suggesting its role as an enhancer in addiction-relevant brain regions, such as the dorsolateral prefrontal cortex and the angular and cingulate gyri. This SNP is also predicted to modify binding scores for several transcription factors. We found modest evidence for replication for rs1409568 in an independent cohort of African American (896 cases and 1591 controls; P=0.03) but not European American (EA; 781 cases and 1905 controls) participants. The combined meta-analysis (3757 cases and 9931 controls) indicated trend-level significance for rs1409568 (P=2.85E-7). No genome-wide significant loci emerged for cannabis dependence criterion count (n=8050). There was also evidence that the minor allele of rs1409568 was associated with a 2.1% increase in right hippocampal volume in an independent sample of 430 EA college students (fwe-P=0.008). The identification and characterization of genome-wide significant loci for cannabis dependence is among the first steps toward understanding the biological contributions to the etiology of this psychiatric disorder, which appears to be rising in some developed nations.

Taxonomic review of the genus Hypomicrogaster Ashmead (Hymenoptera: Braconidae: Microgastrinae), with descriptions of 40 new species.

A taxonomic review of the genus Hypomicrogaster Ashmead is presented with the redescription and redelimitation of the already named species Hypomicrogaster ecus Nixon, H. imitator (Ashmead), H. tydeus Nixon and H. zonaria (Say). The review also implies eleven new synonymies, and a new combination for the species H. areolaris (Blanchard). Also, the present revision identified 40 new Hypomicrogaster species: Hypomicrogaster aodous n. sp., H. aplebis n. sp., H. cernus n. sp., H. crocinus n. sp., H. daktulios n. sp., H. deltis n. sp., H. duo n. sp., H. epipagis n. sp., H. espera n. sp., H. evrys n. sp., H. guille n. sp., H. hektos n. sp., H. hupsos n. sp., H. ingensis n. sp., H. insolitus n. sp., H. inversalis n. sp., H. koinos n. sp., H. largus n. sp., H. laxus n. sp., H. linearis n. sp., H. lineatus n. sp., H. luisi n. sp., H. masoni n. sp., H. mesos n. sp., H. mikrosus n. sp., H. multus n. sp., H. pectinatus n. sp., H. plagios n. sp., H. pollex n. sp., H. rugosus n. sp., H. scindus n. sp., H. sicingens n. sp., H. sicpollex n. sp., H. sicscindus n. sp., H. siderion n. sp., H. spatulae n. sp., H. specialis n. sp., H. tantillus n. sp., H. tetra n. sp., H. zan n. sp. The Hypomicrogaster species are using as hosts 11 families of Lepidoptera, and 52 confirmed lepidopteran species feeding on 34 families of plants. Additionally, a fully illustrated key to all known described species of Hypomicrogaster is presented.

A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53.

Several studies have identified genes associated with alcohol-use disorders (AUDs), but the variation in each of these genes explains only a small portion of the genetic vulnerability. The goal of the present study was to perform a genome-wide association study (GWAS) in extended families from the Collaborative Study on the Genetics of Alcoholism to identify novel genes affecting risk for alcohol dependence (AD). To maximize the power of the extended family design, we used a quantitative endophenotype, measured in all individuals: number of alcohol-dependence symptoms endorsed (symptom count (SC)). Secondary analyses were performed to determine if the single nucleotide polymorphisms (SNPs) associated with SC were also associated with the dichotomous phenotype, DSM-IV AD. This family-based GWAS identified SNPs in C15orf53 that are strongly associated with DSM-IV alcohol-dependence symptom counts (P=4.5 × 10(-8), inflation-corrected P=9.4 × 10(-7)). Results with DSM-IV AD in the regions of interest support our findings with SC, although the associations were less significant. Attempted replications of the most promising association results were conducted in two independent samples: nonoverlapping subjects from the Study of Addiction: Genes and Environment (SAGE) and the Australian Twin Family Study of AUDs (OZALC). Nominal association of C15orf53 with SC was observed in SAGE. The variant that showed strongest association with SC, rs12912251 and its highly correlated variants (D'=1, r(2) 0.95), have previously been associated with risk for bipolar disorder.

Host conservatism, host shifts and diversification across three trophic levels in two Neotropical forests.

Host-parasite systems have been models for understanding the connection between shifts in resource use and diversification. Despite theoretical expectations, ambiguity remains regarding the frequency and importance of host switches as drivers of speciation in herbivorous insects and their parasitoids. We examine phylogenetic patterns with multiple genetic markers across three trophic levels using a diverse lineage of geometrid moths (Eois), specialist braconid parasitoids (Parapanteles) and plants in the genus Piper. Host-parasite associations are mapped onto phylogenies, and levels of cospeciation are assessed. We find nonrandom patterns of host use within both the moth and wasp phylogenies. The moth-plant associations in particular are characterized by small radiations of moths associated with unique host plants in the same geographic area (i.e. closely related moths using the same host plant species). We suggest a model of diversification that emphasizes an interplay of factors including host shifts, vicariance and adaptation to intraspecific variation within hosts.

Family-based mitochondrial association study of traits related to type 2 diabetes and the metabolic syndrome in adolescents.

AIMS/HYPOTHESIS: There has been much focus on the potential role of mitochondria in the aetiology of type 2 diabetes and the metabolic syndrome, and many case-control mitochondrial association studies have been undertaken for these conditions. We tested for a potential association between common mitochondrial variants and a number of quantitative traits related to type 2 diabetes in a large sample of >2,000 healthy Australian adolescent twins and their siblings, many of whom were measured on more than one occasion. METHODS: To the best of our knowledge, this is the first mitochondrial association study of quantitative traits undertaken using family data. The maternal inheritance pattern of mitochondria means established association methodologies are unsuitable for analysis of mitochondrial data in families. We present a methodology, implemented in the freely available program Sib-Pair for performing such an analysis. RESULTS: Despite our study having the power to detect variants with modest effects on these phenotypes, only one significant association was found after correction for multiple testing in any of four age groups. This was for mt14365 with triacylglycerol levels (unadjusted p = 0.0006). This association was not replicated in other age groups. CONCLUSIONS/INTERPRETATION: We find little evidence in our sample to suggest that common European mitochondrial variants contribute to variation in quantitative phenotypes related to diabetes. Only one variant showed a significant association in our sample, and this association will need to be replicated in a larger cohort. Such replication studies or future meta-analyses may reveal more subtle effects that could not be detected here because of limitations of sample size.

Ancestral state reconstruction analysis of hymenopteran sex determination mechanisms.

We provide the first phylogenetic evidence supporting complementary sex determination (CSD) as the ancestral mechanism for haplodiploidy in the Hymenoptera. It is currently not possible, however, to distinguish the evolutionary polarity of single locus (sl) CSD and multiple-locus (ml) CSD given the available data. In this light, we discuss the seemingly maladaptive hypothesis of ml-CSD ancestry, suggesting that collapse from ml-CSD to sl-CSD should remain a viable evolutionary hypothesis based on (i) likely weakening of frequency-dependent selection on sex alleles under ml-CSD and (ii) recent findings with respect to the evolutionary novelty of the complementary sex determiner gene in honeybees. Our findings help provide a phylogenetically informed blueprint for future sampling of sex determination mechanisms in the Hymenoptera, as they yield hypotheses for many unsampled or ambiguous taxa and highlight taxa whose further sampling will influence reconstruction of the evolutionary polarity of sex determination mechanisms in major clades.

The cholinesterases: analysis by pharmacogenomics in man.

We have undertaken a study on variations in cholinesterase (ChE) genes in relation to cardiovascular (CV) function and the metabolic syndrome. Peripheral and central nervous system control of cardiovascular (CV) function mediated through cholinergic pathways is critical in homeostatic maintenance of blood pressure and responsiveness to stress. For acetylcholinesterase (AChE; EC 3.1.1.7) our focus is to identify single nucleotide polymorphisms (SNPs) in the gene that are linked to cardiovascular function. For butyrylcholinesterase (BChE; EC 3.1.1.8) we examined whether BChE activity correlated with parameters of the metabolic syndrome and cardiovascular function. ChE can be found in whole blood enabling a characterization of biochemical phenotype in addition to correlating genotype with phenotypic physiologic responses. Analysis of enzymatic activity was determined spectrophotometrically in blood samples from twin and other subject registries. Correlation analysis revealed significant relationships between enzyme activity and certain CV endpoints. Linkage analysis with data from a dizygotic (DZ) twin set showed a suggestive linkage at the BChE locus, and statistical analysis revealed a high correlation between BChE activity and variables associated with cardiovascular risk and the metabolic syndrome. Pattern of within-pair twin correlations by zygosity and the ACE model-fitting findings suggest the major source of this variation (65%) is attributable to an additive genetic component. To date 19 SNPs have been identified by the re-sequencing of AChE including four nonsynonymous coding SNPs (cSNPs).

Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures.

Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples-the Study of Addictions: Genes and Environment (SAGE; n=2336) and an Australian sample (OZ-ALC; n=5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement.

Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.

Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.

Plasma lipids in twins. Environmental and genetic influences.

A study on 205 pairs of male and females twins, aged from 18 to 34 years. showed significant heritabilities for total and high density lipoprotein cholesterol and for triglycerides. Significant effects of shared environment were also found for total and HDL cholesterol, possibly to a greater extent in women than in men. Triglycerides showed greater variance in men but a model specifying different sized environmental and genetic parameters in the two sexes gave a good fit and indicated that the factors influencing plasma triglycerides are the same in men and women although the effects they produce are scaled differently.

Genetic covariation of neuroticism with monoamine oxidase activity and smoking.

Variation in the personality trait of neuroticism is known to be affected by genetic influences, but despite a number of association studies, the genes involved have not yet been characterized. In a recent study of platelet monoamine oxidase in 1,551 twin subjects, we found a significant association between monoamine oxidase activity and scores on the Eysenck Personality Questionnaire neuroticism scale. Further analyses presented here indicate that both neuroticism and monoamine oxidase activity are associated with variation in smoking habits, and that adjusting for the effect of smoking strengthens the association between MAO and neuroticism. Analysis of the genetic and environmental sources of covariation between neuroticism, smoking, and monoamine oxidase activity show that approximately 8% of the genetic variance in neuroticism is due to the same additive genetic effects that contribute to variation in monoamine oxidase activity, suggesting that variation in neuroticism is associated in part with aspects of serotonin metabolism.

A multivariate assessment of alcohol consumption.

Subjects attending a large, multiphasic health screening centre in Sydney, Australia estimated their alcohol consumption and specimens of their blood were analysed. The most useful univariate estimates of alcohol consumption were erythrocyte mean corpuscular volume and plasma aspartate-aminotransferase, gamma-glutamyl-transpeptidase, triglycerides and uric acid. The most statistically significant of these tests have been combined to form a multivariate predictor of alcohol intake which is more successful in identifying heavy-drinkers than single tests. To describe this population further, and to aid comparisons between populations, information about non-drinkers has also been provided.

Spurious hyperkalaemia and hyponatraemia in a patient with thrombocythaemia.

Changes in serum potassium and sodium during blood clotting in a patient with thrombocythaemia are described. In such patients falsely high results for potassium and falsely low results for sodium may be obtained.

PHYLOGENY OF THE SUBFAMILIES OF THE FAMILY BRACONIDAE (HYMENOPTERA: ICHNEUMONOIDEA): A REASSESSMENT.

Abstract- The recently published phylogeny of Braconidae by Quicke and van Achterberg is reassessed. Character-state definitions and character polarities are evaluated, and more rigorous methods are suggested. Our results indicate that there are many more parsimonious solutions to their data set, the consensus of which differs substantially from their results. Based on our reassessment, little can be said about the relationships among braconid subfamilies. Consensus trees show the cyclostomes as a largely unresolved basal grade. The two other major lineages which have been proposed, the helconoids and microgastroids, are somewhat better resolved, but not consistently so. Relationships among the helconoids vary considerably depending on the parameters used for parsimony analysis.

The effects of diphenylhydantoin on the relationship between high-density lipoprotein cholesterol and several biochemical assays.

Correlations have been calculated between high-density lipoprotein cholesterol and total plasma cholesterol, albumin, gamma-glutamyl transpeptidase, aspartate aminotransferase, alkaline phosphatase, triglyceride, urea, creatinine and uric acid for diphenylhydantoin (DPH) users and for subjects attending a multiphasic health screening centre. For women DPH users, high-density lipoprotein levels correlated significantly with gamma glutamyl transpeptidase, cholesterol and alkaline phosphatase. These correlations were significantly different from those found for male DPH users and from subjects attending the health screening centre. In male DPH users, high-density lipoprotein cholesterol correlates negatively with urea and uric acid levels, a relationship which is found neither in women DPH users nor in the health screening centre population.

Blood pressure and chemistry: some correlations and apparent correlations.

The reported correlation between plasma calcium and blood pressure has been investigated in 412 young men and women. In this sample, it seemed to be due to a stronger correlation between blood pressure and plasma albumin. Blood pressures were also significantly correlated with plasma high-density lipoprotein in men and with plasma uric acid in women.

The effects of inheritance on constituents of plasma: a twin study on some biochemical variables.

Heritability and within-person repeatability of thirteen constituents of plasma were assessed in a study of 206 pairs of male and female twins. Repeat measurements were available on 44 pairs. For bilirubin, calcium, creatinine, phosphate and potassium, the individuality of these characteristics was genetic in origin. Total protein, albumin and globulin showed significant heritability but considerable variation between occasions, while bicarbonate, chloride, iron, sodium and urea showed mainly environmental effects.

Some laboratory correlates of drinking habits.

The effect of drinking habits on the frequency distributions of eight biochemical or haematological test results was studied in 7915 patients attending a multiphasic health testing centre. Increasing incidences of abnormal results with increasing alcohol intake, at levels of alcohol intake habitual for a large proportion of the population, were found for plasma gamma-glutamyl transpeptidase, triglycerides and uric acid, and for erythrocyte mean corpuscular volume. Of four frequently used liver function tests, aspartate aminotransferase, alkaline phosphatase, bilirubin, and albumin, only aspartate aminotransferase was strongly affected by drinking habits. These findings have relevance for the detection of individuals whose drinking habits are harmful to them, and for the interpretation of 'profile' results.

Estimation of alcohol intake from laboratory results.

Subjects with abnormalities in a number of laboratory tests were shown to have higher than usual probabilities of being heavy drinkers. Quantitative estimates have been made of the probabilities of heavy drinking from the results of the following tests: gamma-glutamyl transpeptidase, mean corpuscular volume, uric acid, triglyceride, and aspartate aminotransferase. In men, but not in women, there was a clear increase in this probability with increasing test results for these five tests, which may prove useful in the detection of individuals who are at risk from their drinking habits.