RESUMO
Age estimation based on DNA methylation (DNAm) can be applied to children, adolescents and adults, but many CG dinucleotides (CpGs) exhibit different kinetics of age-associated DNAm across these age ranges. Furthermore, it is still unclear how growth disorders impact epigenetic age predictions, and this may be particularly relevant for a forensic application. In this study, we analyzed buccal mucosa samples from 95 healthy children and 104 children with different growth disorders. DNAm was analysed by pyrosequencing for 22 CpGs in the genes PDE4C, ELOVL2, RPA2, EDARADD and DDO. The relationship between DNAm and age in healthy children was tested by Spearman's rank correlation. Differences in DNAm between the groups "healthy children" and the (sub-)groups of children with growth disorders were tested by ANCOVA. Models for age estimation were trained (1) based on the data from 11 CpGs with a close correlation between DNAm and age (R ≥ 0.75) and (2) on five CpGs that also did not present significant differences in DNAm between healthy and diseased children. Statistical analysis revealed significant differences between the healthy group and the group with growth disorders (11 CpGs), the subgroup with a short stature (12 CpGs) and the non-short stature subgroup (three CpGs). The results are in line with the assumption of an epigenetic regulation of height-influencing genes. Age predictors trained on 11 CpGs with high correlations between DNAm and age revealed higher mean absolute errors (MAEs) in the group of growth disorders (mean MAE 2.21 years versus MAE 1.79 in the healthy group) as well as in the short stature (sub-)groups; furthermore, there was a clear tendency for overestimation of ages in all growth disorder groups (mean age deviations: total growth disorder group 1.85 years, short stature group 1.99 years). Age estimates on samples from children with growth disorders were more precise when using a model containing only the five CpGs that did not present significant differences in DNAm between healthy and diseased children (mean age deviations: total growth disorder group 1.45 years, short stature group 1.66 years). The results suggest that CpGs in genes involved in processes relevant for growth and development should be avoided in age prediction models for children since they may be sensitive for alterations in the DNAm pattern in cases of growth disorders.
Assuntos
Metilação de DNA , Epigênese Genética , Adolescente , Adulto , Criança , Pré-Escolar , Ilhas de CpG/genética , Transtornos do Crescimento/genética , Humanos , Lactente , Mucosa BucalRESUMO
As a contribution to the discussion about the possible effects of ethnicity/ancestry on age estimation based on DNA methylation (DNAm) patterns, we directly compared age-associated DNAm in German and Japanese donors in one laboratory under identical conditions. DNAm was analyzed by pyrosequencing for 22 CpG sites (CpGs) in the genes PDE4C, RPA2, ELOVL2, DDO, and EDARADD in buccal mucosa samples from German and Japanese donors (N = 368 and N = 89, respectively).Twenty of these CpGs revealed a very high correlation with age and were subsequently tested for differences between German and Japanese donors aged between 10 and 65 years (N = 287 and N = 83, respectively). ANCOVA was performed by testing the Japanese samples against age- and sex-matched German subsamples (N = 83 each; extracted 500 times from the German total sample). The median p values suggest a strong evidence for significant differences (p < 0.05) at least for two CpGs (EDARADD, CpG 2, and PDE4C, CpG 2) and no differences for 11 CpGs (p > 0.3).Age prediction models based on DNAm data from all 20 CpGs from German training data did not reveal relevant differences between the Japanese test samples and German subsamples. Obviously, the high number of included "robust CpGs" prevented relevant effects of differences in DNAm at two CpGs.Nevertheless, the presented data demonstrates the need for further research regarding the impact of confounding factors on DNAm in the context of ethnicity/ancestry to ensure a high quality of age estimation. One approach may be the search for "robust" CpG markers-which requires the targeted investigation of different populations, at best by collaborative research with coordinated research strategies.
Assuntos
Metilação de DNA , Mucosa Bucal , Adolescente , Adulto , Idoso , Biomarcadores , Criança , Ilhas de CpG , Humanos , Japão , Pessoa de Meia-Idade , Adulto JovemRESUMO
Animal domestication and artificial selection give rise to gradual changes at the genomic level in populations. Subsequent footprints of selection, known as selection signatures or selective sweeps, have been traced in the genomes of many animal livestock species by exploiting variation in linkage disequilibrium patterns and/or reduction of genetic diversity. Domestication of most aquatic species is recent in comparison with land animals, and salmonids are one of the most important fish species in aquaculture. Coho salmon (Oncorhynchus kisutch), cultivated primarily in Chile, has been subjected to breeding programs to improve growth, disease resistance traits, and flesh color. This study aimed to identify selection signatures that may be involved in adaptation to culture conditions and traits of productive interest. To do so, individuals of two domestic populations cultured in Chile were genotyped with 200 thousand SNPs, and analyses were conducted using iHS, XP-EHH and CLR. Several signatures of selection on different chromosomal regions were detected across both populations. Some of the identified regions under selection contained genes such anapc2, alad, chp2 and myn, which have been previously associated with body weight in Atlantic salmon, or sec24d and robo1, which have been associated with resistance to Piscirickettsia salmonis in coho salmon. Findings in our study can contribute to an integrated genome-wide map of selection signatures, to help identify the genetic mechanisms of phenotypic diversity in coho salmon.
Assuntos
Aquicultura , Estudo de Associação Genômica Ampla , Oncorhynchus kisutch/genética , Animais , Doenças dos Peixes/microbiologia , Genótipo , Humanos , Oncorhynchus kisutch/microbiologia , Fenótipo , Piscirickettsia/patogenicidade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Carotenoids are primarily responsible for the characteristic red flesh coloration of salmon. Flesh coloration is an economically and evolutionarily significant trait that varies inter- and intra-specifically, yet the underlying genetic mechanism is unknown. Chinook salmon (Oncorhynchus tshawytscha) represents an ideal system to study carotenoid variation as, unlike other salmonids, they exhibit extreme differences in carotenoid utilization due to genetic polymorphisms. Here, we crossed populations of Chinook salmon with fixed differences in flesh coloration (red versus white) for a genome-wide association study to identify loci associated with pigmentation. Here, the beta-carotene oxygenase 2-like (BCO2-l) gene was significantly associated with flesh colour, with the most significant single nucleotide polymorphism explaining 66% of the variation in colour. BCO2 gene disruption is linked to carotenoid accumulation in other taxa, therefore we hypothesize that an ancestral mutation partially disrupting BCO2-l activity (i.e. hypomorphic mutation) allowed the deposition and accumulation of carotenoids within Salmonidae. Indeed, we found elevated transcript levels of BCO2-l in white Chinook salmon relative to red. The long-standing mystery of why salmon are red, while no other fishes are, is thus probably explained by a hypomorphic mutation in the proto-salmonid at the time of divergence of red-fleshed salmonid genera (approx. 30 Ma).
Assuntos
Carotenoides/metabolismo , Pigmentação/genética , Salmão/fisiologia , Animais , Aptidão Genética , Polimorfismo GenéticoRESUMO
Cardiac implantable electronic devices have been successfully treating patients with brady- and tachyarrhythmias for decades. However, there are still significant complications related to this therapy modality, many related to the transvenous lead. Paradigm-shifting technologies, such as the subcutaneous implantable cardioverter-defibrillator (S-ICD) and leadless cardiac pacemakers (LCP), have emerged to address these complications. The novel modular cardiac rhythm management (mCRM) system, consisting of a communicating antitachycardia pacing-enabled LCP and SICD, is the first system to integrate wireless intrabody communication between devices to allow for coordination of leadless pacing and defibrillator therapy delivery. In this review, the design and concept of the mCRM system are presented and available evidence is summarized.
Assuntos
Desfibriladores Implantáveis , Marca-Passo Artificial , Humanos , TaquicardiaRESUMO
A fundamental component of any magnetically confined fusion experiment is a firm understanding of the magnetic field. The increased complexity of the C-2W machine warrants an equally enhanced diagnostic capability. C-2W is outfitted with over 700 magnetic field probes of various types. They are both internal and external to the vacuum vessel. Inside, a linear array of innovative in-vacuum annular flux loop/B-dot combination probes provide information about plasma shape, size, pressure, energy, temperature, and trapped flux when coupled with established theoretical interpretations. A linear array of B-dot probes complement the azimuthally averaged measurements. A Mirnov array of 64 3D probes, with both low and high frequency resolution, detail plasma motion and MHD modal content via singular value decomposition analysis. Internal Rogowski probes measure axial currents flowing in the plasma jet. Outside, every feed-through for an internal probe has an external axial field probe. There are many external loops that measure the plasma formation dynamics and the total external magnetic flux. The external measurements are primarily used to characterize eddy currents in the vessel during a plasma shot. Details of these probes and the data derived from their signals are described.
RESUMO
A suite of diagnostics was developed to measure particle and heat fluxes arriving at the divertor electrodes of the C-2W experiment at TAE Technologies. The divertor electrodes consist of 4 concentric rings, each equipped with a bolometer, electrostatic energy analyzer, and thermocouple mounted at two opposing azimuthal locations. These probes provide measurements of the power flux to the divertor electrodes as well as measurements of the ion current density, ion energy distribution, and total energy deposition. The thermocouples also provide calibration points for inferring the heat deposition profile via thermographic imaging of the electrodes with a fast infrared camera. The combined measurements enable the calculation of the energy lost per escaping electron/ion pair, which is an important metric for understanding electron heat transport in the open field lines that surround the field-reversed configuration plasma in C-2W.
RESUMO
The endoplasmic reticulum (ER) serves as the major intracellular Ca(2+) store and has a role in the synthesis and folding of proteins. BAX (BCL2-associated X protein) inhibitor-1 (BI-1) is a Ca(2+) leak channel also implicated in the response against protein misfolding, thereby connecting the Ca(2+) store and protein-folding functions of the ER. We found that BI-1-deficient mice suffer from leukopenia and erythrocytosis, have an increased number of splenic marginal zone B cells and higher abundance and nuclear translocation of NF-κB (nuclear factor-κ light-chain enhancer of activated B cells) proteins, correlating with increased cytosolic and ER Ca(2+) levels. When put into culture, purified knockout T cells and even more so B cells die spontaneously. This is preceded by increased activity of the mitochondrial initiator caspase-9 and correlated with a significant surge in mitochondrial Ca(2+) levels, suggesting an exhausted mitochondrial Ca(2+) buffer capacity as the underlying cause for cell death in vitro. In vivo, T-cell-dependent experimental autoimmune encephalomyelitis and B-cell-dependent antibody production are attenuated, corroborating the ex vivo results. These results suggest that BI-1 has a major role in the functioning of the adaptive immune system by regulating intracellular Ca(2+) homeostasis in lymphocytes.
Assuntos
Linfócitos B/imunologia , Proteínas de Membrana/fisiologia , Linfócitos T/imunologia , Transporte Ativo do Núcleo Celular , Animais , Apoptose , Linfócitos B/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio , Caspases/metabolismo , Sobrevivência Celular , Citoplasma/metabolismo , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Retículo Endoplasmático/metabolismo , Ativação Enzimática , Feminino , Leucopenia/genética , Leucopenia/imunologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Obesidade/genética , Obesidade/imunologia , Baço/imunologia , Baço/patologia , Linfócitos T/metabolismoRESUMO
We investigate nanopillars in which two thin ferromagnetic particles are separated by a nanometer thin nonmagnetic spacer and can be set into stable spin vortex-pair configurations. We find that the previously unexplored limit of strong vortex core-core coupling can dominate the spin dynamics in the system. We observe experimentally and explain analytically and numerically how the 0.2 GHz gyrational resonance modes of the individual vortices are transformed into a 2 GHz collective rotational resonance mode in the configurations where the two cores form a bound pair.
RESUMO
It has been hypothesized that salmonids use olfactory cues to return to their natal rivers and streams. The key components of the molecular pathways involved in imprinting and homing, however, are still unknown. Aquatic chemical cues are received through the nares and into the nasal cavity that contains a single olfactory organ, the olfactory rosette. The olfactory rosette contains sensory neurons, each of which is thought to express only one olfactory receptor. If odorants are involved in salmonid homing migration then olfactory receptors should play a critical role in the dissipation of information from the environment to the fish. Therefore, to understand the molecular basis for imprinting and homing in Atlantic salmon Salmo salar it is important to identify and characterize the repertoire of olfactory receptors in this species. The first public assembly of the S. salar genome was searched for genes encoding three of the superfamilies of fish olfactory receptors: V2R-like (olfc), V1R-like (ora) and main olfactory receptor (mor). A further six ora genes were added to ora1 and ora2, which had been described previously. In addition, 48 putative mors were identified, 24 of which appear to be functional based on their gene structures and predicted amino-acid sequences. Phylogenetic analyses were then used to compare these S. salar olfactory receptor genes with those of zebrafish Danio rerio, two pufferfish species Takifugu rubripes and Tetraodon nigroviridis, medaka Oryzias latipes and three-spined stickleback Gasterosteus aculeatus.
Assuntos
Proteínas de Peixes/genética , Receptores Odorantes/genética , Salmo salar/genética , Animais , Mapeamento Cromossômico , Bases de Dados Genéticas , Filogenia , Análise de Sequência de ProteínaRESUMO
The magnetic decay time of a synthetic antiferromagnet comprised of two closely spaced magnetic dipoles is measured in the presence of microwave excitation. The system is known to be highly stable with respect to switching between its two antiparallel ground states under quasistatic magnetic fields. We show that an order of magnitude lower field can switch the pair, provided the field is applied in resonance with the optical eigenmode of the collective spin dynamics in the system. We furthermore show that thermal agitation can play an essential role in spin-flop switching for resonant excitations of near- or subcritical amplitude.
RESUMO
It has been hypothesized that salmonids use olfactory cues to return to their natal rivers and streams. However, the key components of the molecular pathway involved in imprinting and homing are still unknown. If odorants are involved in salmon homing migration, then olfactory receptors should play a critical role in the dissipation of information from the environment to the fish. Therefore, we examined the expression profiles of a suite of genes encoding olfactory receptors and other olfactory-related genes in the olfactory rosettes of different life stages in two anadromous and one non-anadromous wild Atlantic salmon populations from Newfoundland, Canada. We identified seven differentially expressed OlfC genes in juvenile anadromous salmon compared to returning adults in both populations of anadromous Atlantic salmon. The salmon from the Campbellton River had an additional 10 genes that were differentially expressed in juveniles compared to returning adults. There was no statistically significant difference in gene expression of any of the genes in the non-anadromous population (P < 0.01). The function of the OlfC gene products is not clear, but they are predicted to be amino acid receptors. Other studies have suggested that salmon use amino acids for imprinting and homing. This study, the first to examine the expression of olfactory-related genes in wild North American Atlantic salmon, has identified seven OlfC genes that may be involved in the imprinting and homeward migration of anadromous Atlantic salmon.
Assuntos
Proteínas de Peixes/metabolismo , Receptores Odorantes/metabolismo , Salmo salar/metabolismo , Migração Animal , Animais , Proteínas de Peixes/genética , Comportamento de Retorno ao Território Vital , Fixação Psicológica Instintiva/fisiologia , Terra Nova e Labrador , Salmo salar/crescimento & desenvolvimento , Salmo salar/fisiologiaRESUMO
The ability of rainbow trout (Oncorhynchus mykiss) to respond successfully to infection by viral hemorrhagic septicaemia virus (VHSV) is expected to involve a large number of biochemical processes. We hypothesized that this would be reflected at the gene expression level in infected fish, and we tested it by examining gene expression levels in the head kidney of trout at a genome-wide scale with a 16K cDNA microarray for salmonids. Expression levels were recorded during 16 days following bath challenge. The challenge experiment included a relatively low susceptibility (32% survival following challenge) and a relatively high susceptibility (18% survival following challenge) trout family that were both split into a group exposed to virus and a non-exposed control group. In total, 939 genes were differentially expressed between infected and non-infected fish (FDR p=0.05). Five groups of Gene Ontology categories were involved in immune-related processes and over-represented in infected fish: (i) stress and defense response, (ii) NFkappaB signal transduction, (iii) response to non-self, (iv) antigen processing and presentation, and (v) proteasome complexes. The first four categories were also over-represented among the 642 differentially expressed genes in the low-susceptibility trout family but not among the 556 differentially expressed genes in the high-susceptibility trout family. Expression profiles for most immune genes discussed showed increased transcription from day 3 post-challenge. The results suggest that the innate immune system may play an important role in the successful response to VHSV in rainbow trout. In addition, the results indicate that a superior regulation of the transcription of several key innate immune-related genes contribute to the increased survival in resistant fish.
Assuntos
Perfilação da Expressão Gênica , Novirhabdovirus/fisiologia , Oncorhynchus mykiss/genética , Oncorhynchus mykiss/virologia , Animais , Interações Hospedeiro-Patógeno , Imunidade Inata/genética , Rim/metabolismo , Rim/virologia , Análise de Sequência com Séries de Oligonucleotídeos , Fatores de TempoRESUMO
Males are the heterogametic sex in salmonid fishes. In brown trout (Salmo trutta) the sex-determining locus, SEX, has been mapped to the end of linkage group BT-28, which corresponds to linkage group AS-8 and chromosome SSA15 in Atlantic salmon (Salmo salar). We set out to identify the sex chromosomes in brown trout. We isolated Atlantic salmon BAC clones containing microsatellite markers that are on BT-28 and also on AS-8, and used these BACs as probes for fluorescent in situ hybridization (FISH) analysis. SEX is located on the short arm of a small subtelocentric/acrocentric chromosome in brown trout, which is consistent with linkage analysis. The acrocentric chromosome SSA15 in Atlantic salmon appears to have arisen by a centric fusion of 2 small acrocentric chromosomes in the common ancestor of Salmo sp. We speculate that the fusion process that produced Atlantic salmon chromosome SSA15 disrupted the ancestral sex-determining locus in the Atlantic salmon lineage, providing the impetus either for the relocation of SEX or selection pressure for a novel sex-determining gene to arise in this species. Thus, the sex-determining genes may differ in Atlantic salmon and brown trout.
Assuntos
Oncorhynchus mykiss/genética , Salmo salar/genética , Salmonidae/genética , Cromossomos Sexuais , Animais , Feminino , MasculinoRESUMO
The phylogenetic relationships among the three subfamilies (Salmoninae, Coregoninae and Thymallinae) in the Salmonidae have not been addressed extensively at the molecular level. In this study, the whole mitochondrial genomes of two Thymallinae species, Thymallus arcticus and Thymallus thymallus were sequenced, and the published mitochondrial genome sequences of other salmonids were used for Bayesian and maximum-likelihood phylogenetic analyses. These results support an ancestral Coregoninae, branching within the Salmonidae, with Thymallinae as the sister group to Salmoninae.
Assuntos
Genoma Mitocondrial/genética , Filogenia , Salmonidae/classificação , Salmonidae/genética , Animais , Dados de Sequência MolecularRESUMO
Salmonids are descended from a common ancestor that underwent an autotetraploidization event. After a whole genome duplication species could deal with sex determination by deleting one copy of SEX, the sex determining locus, or by recruiting a duplicated transcription factor to become a novel sex determining gene. It is not known which if any of these strategies salmonids adopted, but it appears that they all have primarily a genetic mechanism of sex determination with male heterogamety. The sharing of sex-linked markers on the X and Y chromosomes and the difficulty in identifying Y-specific markers indicate that X and Y chromosomes in salmonids have a large pseudoautosomal region and a small sex determining region. Linkage analyses suggest that either SEX differs in different lineages or else has remained the same and moved by transposition to different chromosomes. The identification of the sex chromosomes in salmonid species has not resolved this issue. It is clear that salmonids are at an early stage in sex chromosome differentiation and therefore provide a wonderful opportunity to study the evolution of sex determination. The availability of a reference salmonid genome sequence would provide an important resource for research in this area.
Assuntos
Salmonidae/genética , Cromossomos Sexuais/genética , Processos de Determinação Sexual , Animais , Mapeamento Cromossômico , Duplicação Gênica , Hibridização in Situ FluorescenteRESUMO
Genomic resources in rainbow smelt (Osmerus mordax) enable us to examine the genome duplication process in salmonids and test hypotheses relating to the fate of duplicated genes. They further enable us to pursue physiological and ecological studies in smelt. A bacterial artificial chromosome library containing 52,410 clones with an average insert size of 146 kb was constructed. This library represents an 11-fold average coverage of the rainbow smelt (O. mordax) genome. In addition, several complementary deoxyribonucleic acid libraries were constructed, and 36,758 sequences were obtained and combined into 12,159 transcripts. Over half of these transcripts have been identified, several of which have been associated with cold adaptation. These basic resources show high levels of similarity (86%) to salmonid genes and provide initial support for genome duplication in the salmonid ancestor. They also facilitate identification of genes important to fish and direct us toward new technologies for other studies in fish biology.
Assuntos
Etiquetas de Sequências Expressas , Biblioteca Genômica , Osmeriformes/genética , Animais , Cromossomos Artificiais Bacterianos/genética , Temperatura Baixa , Bases de Dados Genéticas , Proteínas de Peixes/genética , Biblioteca Gênica , Dados de Sequência MolecularRESUMO
Several important cultured marine fish are highly susceptible to an ectoparasitic condition known as amoebic gill disease (AGD). In AGD-affected fish, modulation of IL-1beta, p53 and p53-regulated transcripts is restricted to the (multi)focal AGD-associated gill lesions. To determine whether this lesion-restricted modulation of transcripts occurs on a transcriptome-wide scale and to identify mechanisms that underpin the susceptibility of fish to AGD, we compared the transcriptome of AGD lesions with "normal" tissue from AGD-affected and healthy individuals. Global gene expression profiling using a 16K salmonid microarray, revealed a total of 176 significantly regulated annotated features and of those, the modulation of 99 (56%) was lesion-restricted. Annotated transcripts were classified according to functional gene ontology. Within the immune response category, transcripts were almost universally down-regulated. In AGD-affected tissue, significant, coordinated down-regulation of the major histocompatibility complex class I (MHC I) pathway-related genes occurred during the later stages of infection and appeared to be mediated by down-regulation of interferon-regulatory factor (IRF)-1, independent of interferon-alpha, interferon-gamma and IRF-2 expression. Within this micro-environment, suppression of the MHC I and possibly the MHC II pathways may inhibit the development of acquired immunity and could explain the unusually high susceptibility of Atlantic salmon to AGD.
Assuntos
Amebíase/veterinária , Amébidos , Apresentação de Antígeno/genética , Doenças dos Peixes/imunologia , Brânquias/imunologia , Salmo salar , Amebíase/genética , Amebíase/imunologia , Amebíase/parasitologia , Animais , Regulação para Baixo , Doenças dos Peixes/genética , Doenças dos Peixes/parasitologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/metabolismo , Perfilação da Expressão Gênica , Genes MHC Classe I , Genes MHC da Classe II , Brânquias/metabolismo , Brânquias/parasitologia , Fator Regulador 1 de Interferon/metabolismo , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Salmo salar/genética , Salmo salar/imunologia , Salmo salar/parasitologia , Proteína Supressora de Tumor p53/metabolismoRESUMO
As more salmon gene expression data has become available, the cDNA microarray platform has emerged as an appealing alternative in ecotoxicological screening of single chemicals and environmental samples relevant to the aquatic environment. This study was performed to validate biomarker gene responses of in vitro cultured rainbow trout (Oncorhynchus mykiss) hepatocytes exposed to model chemicals, and to investigate effects of mixture toxicity in a synthetic mixture. Chemicals used for 24h single chemical- and mixture exposures were 10 nM 17alpha-ethinylestradiol (EE2), 0.75 nM 2,3,7,8-tetrachloro-di-benzodioxin (TCDD), 100 microM paraquat (PQ) and 0.75 microM 4-nitroquinoline-1-oxide (NQO). RNA was isolated from exposed cells, DNAse treated and quality controlled before cDNA synthesis, fluorescent labelling and hybridisation to a 16k salmonid microarray. The salmonid 16k cDNA array identified differential gene expression predictive of exposure, which could be verified by quantitative real time PCR. More precisely, the responses of biomarker genes such as cytochrome p4501A and UDP-glucuronosyl transferase to TCDD exposure, glutathione reductase and gammaglutamyl cysteine synthetase to paraquat exposure, as well as vitellogenin and vitelline envelope protein to EE2 exposure validated the use of microarray applied to RNA extracted from in vitro exposed hepatocytes. The mutagenic compound NQO did not result in any change in gene expression. Results from exposure to a synthetic mixture of the same four chemicals, using identical concentrations as for single chemical exposures, revealed combined effects that were not predicted by results for individual chemicals alone. In general, the response of exposure to this mixture led to an average loss of approximately 60% of the transcriptomic signature found for single chemical exposure. The present findings show that microarray analyses may contribute to our mechanistic understanding of single contaminant mode of action as well as mixture effects, but that its use in screening of complex environmental samples will need to be further evaluated.