Genetic variants in or near miRNA genes can have profound effects on miRNA expression and targeting. As user-friendly software for the impact prediction of miRNA variants on a large scale is still lacking, we created a tool called miRVaS.... more
Genetic variants in or near miRNA genes can have profound effects on miRNA expression and targeting. As user-friendly software for the impact prediction of miRNA variants on a large scale is still lacking, we created a tool called miRVaS. miRVaS automates this prediction by annotating the location of the variant relative to functional regions within the miRNA hairpin (seed, mature, loop, hairpin arm, flanks) and by annotating all predicted structural changes within the miRNA due to the variant. In addition, the tool defines the most important region that is predicted to have structural changes and calculates a conservation score that is indicative of the reliability of the structure prediction. The output is presented in a tab-separated file, which enables fast screening, and in an html file, which allows visual comparison between wild-type and variant structures. All separate images are provided for downstream use. Finally, we tested two different approaches on a small test set of ...
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miRNAs are small (~22 nt) noncoding RNAs that are important regulators of gene expression. The latest release of miRBase (15.0) contains 940 human miRNA sequences of which several are already implicated in human diseases such as... more
miRNAs are small (~22 nt) noncoding RNAs that are important regulators of gene expression. The latest release of miRBase (15.0) contains 940 human miRNA sequences of which several are already implicated in human diseases such as Tourette's symdrome, autism, schizophrenia, .... Materials and Methods We developed a miRNA prediction pipeline that integrates different programs to predict novel miRNAs in genomic regions associated with psychiatric diseases. In total we used 8 different miRNA prediction programs for the construction of our miRNA prediction pipeline. Predictions of all programs were clustered to form consensus predictions and a score was allocated to each prediction based on the number of different programs supporting the prediction. We used available Next Generation Sequencing data to validate the obtained predictions. Results We ran our pipeline on 15 genomic regions, all of which are associated or linked to psychiatric diseases. The total size of these regions is ap...
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Research Interests: Genetics, Psychology, Medicine, Psychiatric Genetics, Humans, and 12 moreChild, Vasopressin, Female, Male, Clinical Sciences, Single Nucleotide Polymorphism, Arginine, Neurosciences, HUMAN MEDICINE, Attention deficit disorder with hyperactivity, Attention deficit hyperactivity disorder, and Arginine Vasopressin
Research Interests: Microbiology, Biology, Quantification, Medicine, Food Microbiology, and 15 moreEscherichia coli, Animals, Listeria monocytogenes, Polymerase Chain Reaction, multiplex PCR, Cattle, Farm, Isolation, Feces, Dairying, E Coli, Predictive value of tests, Escherichia Coli Infections, cattle diseases, and Enterohemorrhagic Escherichia coli
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Caspase-14, an important proteinase involved in filaggrin catabolism, is mainly active in terminally differentiating keratinocytes, where it is required for the generation of skin natural moisturizing factors (NMFs). Consequently,... more
Caspase-14, an important proteinase involved in filaggrin catabolism, is mainly active in terminally differentiating keratinocytes, where it is required for the generation of skin natural moisturizing factors (NMFs). Consequently, caspase-14 deficient epidermis is characterized by reduced levels of NMFs such as urocanic acid and 2-pyrrolidone-5-carboxylic acid. Patients suffering from filaggrin deficiency are prone to develop atopic dermatitis, which is accompanied with increased microbial burden. Among several reasons, this effect could be due to a decrease in filaggrin breakdown products. In this study, we found that caspase-14(-/-) mice show enhanced antibacterial response compared to wild-type mice when challenged with bacteria. Therefore, we compared the microbial communities between wild-type and caspase-14(-/-) mice by sequencing of bacterial 16S ribosomal RNA genes. We observed that caspase-14 ablation leads to an increase in bacterial richness and diversity during steady-state conditions. Although both wild-type and caspase-14(-/-) skin were dominated by the Firmicutes phylum, the Staphylococcaceae family was reduced in caspase-14(-/-) mice. Altogether, our data demonstrated that caspase-14 deficiency causes the imbalance of the skin-resident bacterial communities.
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The accessibility of genome-wide screening technologies considerably facilitated the identification and characterization of copy number variations (CNVs). The increasing amount of available data describing these variants, clearly... more
The accessibility of genome-wide screening technologies considerably facilitated the identification and characterization of copy number variations (CNVs). The increasing amount of available data describing these variants, clearly demonstrates their abundance in the human genome. This observation shows that not only SNPs, but also CNVs and other structural variants strongly contribute to genetic variation. Even though not all structural variants have an obvious phenotypic effect, there is evidence that CNVs influence gene dosage and hence can have profound effects on human disease susceptibility, disease manifestation, and disease severity. Therefore, CNV screening and analysis methodologies, specifically focusing on disease-related CNVs are actively progressing. This chapter specifically describes different techniques currently available for the targeted screening and validation of CNVs. We not only provide an overview of all these CNV analysis methods, but also address their strong and weak points. Methods covered include fluorescence in situ hybridization (FISH), quantitative real-time PCR (qPCR), paralogue ratio test (PRT), molecular copy-number counting (MCC), and multiplex PCR-based approaches, such as multiplex amplifiable probe hybridization (MAPH), multiplex ligation-dependent probe amplification (MLPA), multiplex PCR-based real-time invader assay (mPCR-RETINA), quantitative multiplex PCR of short fluorescent fragments (QMPSF), and multiplex amplicon quantification (MAQ). We end with some general remarks and conclusions, furthermore briefly addressing the future perspectives.
Research Interests: Genetics, Computational Biology, Biology, Medicine, Humans, and 13 moreFluorescence in situ hybridization, Nucleic acid hybridization, Gene Dosage, Human Genome, Copy Number Variation, Single Nucleotide Polymorphism, Multiplex, Amplicon, HUMAN MEDICINE, Biochemistry and cell biology, Validation Studies as Topic, real time polymerase chain reaction, and multiplex polymerase chain reaction
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Research Interests: Genetics, Depression, Biology, Humans, Major Depressive Disorder, and 15 moreHaplotypes, Female, Male, Enzyme, Major Depression, Immune system, Adult, Linkage Disequilibrium, Kynurenine pathway, HUMAN MEDICINE, Haplotype, Association Analysis, Gene frequency, Kynurenic acid, and Major Depressive Episode
Corticotropin-releasing factor-binding protein regulates the availability of free corticotropin-releasing factor and is a functional candidate gene for affective disorders. The aim of this study was to examine the association between... more
Corticotropin-releasing factor-binding protein regulates the availability of free corticotropin-releasing factor and is a functional candidate gene for affective disorders. The aim of this study was to examine the association between polymorphisms in CRF-BP gene and bipolar disorder in an isolated Swedish population. One hundred and eighty-two patients with bipolar I disorder and 333 controls from Northern Sweden were included in the study. Five single nucleotide polymorphisms and a deletion polymorphism in the CRF-BP gene were genotyped. The haplotype block structure of the gene was considered and the expectation maximization algorithm was adopted to estimate the haplotype frequencies. As a result, there were no significant associations of the different polymorphisms in the CRF-BP gene with bipolar disorder. In conclusion, this study in an isolated Swedish population does not support a role for the CRF-BP gene in the vulnerability for bipolar disorder.
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The co-segregation in one pedigree of bipolar affective disorder with... more
The co-segregation in one pedigree of bipolar affective disorder with Darier's disease whose gene is on chromosome 12q23-q24.1, and findings from linkage and association studies with the neighbouring gene of phospholipase A2 (PLA2) indicate that PLA2 may be considered as a candidate gene for affective disorders. All relevant genetic association studies, however, were conducted on bipolar patients. In the present study, the possible association between the PLA2 gene and unipolar affective disorder was examined on 321 unipolar patients and 604 controls (all personally interviewed), recruited from six countries (Belgium, Bulgaria, Croatia, Germany, Greece, and Italy) participating in the European Collaborative Project on Affective Disorders. After controlling for population group and gender, one of the eight alleles of the investigated marker (allele 7) was found to be more frequent among unipolar patients with more than three major depressive episodes than among controls (P<0.01); genotypic association was also observed, under the dominant model of genetic transmission (P<0.02). In addition, presence of allele 7 was correlated with a higher frequency of depressive episodes (P<0.02). These findings suggest that structural variations at the PLA2 gene or the chromosomal region around it may confer susceptibility for unipolar affective disorder.
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Research Interests: Genetics, Bipolar Disorder, Biology, Medicine, Psychiatric Genetics, and 15 moreMood, Humans, Europe, Clinical Sciences, Mood Disorders, Genetic Polymorphism, Psychiatric, Genetic Association, Case Control Study, Allele, Mood Disorder, Neurosciences, Case Control Studies, Gene frequency, and population stratification
... Han Asard Corresponding Author Contact Information , E-mail The Corresponding Author , a , Javier Terol-Alcayde b , Valeria Preger c , Jurgen Del Favero d , Wim Verelst a , Francesca Sparla c , Manuel Pérez-Alonso b and Paolo Trost c.... more
... Han Asard Corresponding Author Contact Information , E-mail The Corresponding Author , a , Javier Terol-Alcayde b , Valeria Preger c , Jurgen Del Favero d , Wim Verelst a , Francesca Sparla c , Manuel Pérez-Alonso b and Paolo Trost c. ... On the other hand, Perin et al. ...
Research Interests: Biochemistry, Plant Biology, Biology, Arabidopsis thaliana, Homology Modeling, and 15 moreGenome Analysis, Electron Transport, Arabidopsis, Animal Protein, Cytochrome B, Ascorbic Acid, Amino Acid Sequence, Open Reading Frame, In Silico, Membrane Protein, Higher Plants, Ascorbate, B, Binding Site, and DNA sequence
Research Interests: Computer Science, Biology, Medicine, Annotation, Biological Sciences, and 15 moreSoftware, Environmental Sciences, Primer design, Polymerase Chain Reaction, Genome, Nucleic Acids, Computer User Interface Design, Web Service, Very high throughput, Large Scale, Web Server, Amplicon, Internet, Software Package, and Failure rate
Research Interests: Genetics, Immunology, Complement activation, Inflammation, Adolescent, and 15 moreMedicine, Complement System, Humans, Child, Endothelial Cells, Mutation, Hemolytic Uremic Syndrome, Middle Aged, Myocardial Infarction, Adult, New England, HUMAN MEDICINE, Atypical Hemolytic Uremic Syndrome, DNA mutational analysis, and Medical and Health Sciences
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Research Interests: Cognitive Science, Functional Analysis, Biology, Motor neuron, Medicine, and 15 moreGene expression, In Situ Hybridization, Molecular and cellular biology, Mice, Animals, Peripheral Nervous System, Gene, Gene Structure, Genomic Library, Cellular and Molecular Neuroscience, Genetic Markers, Neurosciences, Differential Gene Expression, Gene expression profiling, and Expression pattern
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Severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) is a rare disorder occurring in young children often without a family history of a similar disorder. The earliest disease manifestations are usually fever-associated seizures.... more
Severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) is a rare disorder occurring in young children often without a family history of a similar disorder. The earliest disease manifestations are usually fever-associated seizures. Later in life, patients display different types of afebrile seizures including myoclonic seizures. Arrest of psychomotor development occurs in the second year of life and most patients become ataxic. Patients are resistant to antiepileptic drug therapy. Recently, we described de novo mutations of the neuronal sodium channel alpha-subunit gene SCN1A in seven isolated SMEI patients. To investigate the contribution of SCN1A mutations to the etiology of SMEI, we examined nine additional SMEI patients. We observed eight coding and one noncoding mutation. In contrast to our previous study, most mutations are missense mutations clustering in the S4-S6 region of SCN1A. These findings demonstrate that de novo mutations in SCN1A are a major cause of isolated SMEI.
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For more than 20 years already, researchers from all over the world have tried to get insight into the genetic basis of psychiatric disorders such as schizophrenia (SZ) and bipolar (BP) disorder. Linkage and candidate gene association... more
For more than 20 years already, researchers from all over the world have tried to get insight into the genetic basis of psychiatric disorders such as schizophrenia (SZ) and bipolar (BP) disorder. Linkage and candidate gene association study results have led to a range of hypotheses about the pathogenesis of the disorders, but overall genetic findings have been inconsistent and not a single functional risk causing variant has yet been identified. Even genomewide association (GWA) studies in large samples, the most extensive and systematic interrogation of the genome thus far, seemingly have not brought the expected answers. A reasonable interpretation is that multiple rare variants, inherently linked with locus and allelic heterogeneity, confer a substantial proportion of susceptibility to the disorders. Also, structural variation might be an important factor and promising results are arising from copy-number variation (CNV) analyses. In this review we shortly touch on "old" results from linkage and association studies and critically review the design and "new" results of GWA and CNV studies. We discuss what can be learned from the past and how this knowledge can be used in future study designs.
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The TNFRSF6 gene is not implicated in familial early-onset Alzheimer's disease. ... Theuns J, Feuk L, Dermaut B, Del-Favero J, Roks G, Van den Bossche D, Corsmit E, Van den Broeck M, van Duijn... more
The TNFRSF6 gene is not implicated in familial early-onset Alzheimer's disease. ... Theuns J, Feuk L, Dermaut B, Del-Favero J, Roks G, Van den Bossche D, Corsmit E, Van den Broeck M, van Duijn CM, Cruts M, Brookes AJ, Van Broeckhoven C. ... Department of Molecular ...
Research Interests: Genetics, Human Genetics, Polymorphism, Complementary and Alternative Medicine, Biology, and 14 moreApoptosis, Human, Humans, Disease, Gene, Phenotype, Apoptose, Family Health, Genotype, Presenilin-2, Medicine and Health Sciences, Alzheimer Disease, Age of Onset, and Paediatrics and reproductive medicine
Research Interests: Genetics, Human Genetics, Polymorphism, Complementary and Alternative Medicine, Biology, and 15 moreMedicine, Humans, Polymerase Chain Reaction, Cerebellar ataxia, Gene, Introns, Intron, Ataxia, Base Sequence, Exon, Long Distance, Molecular Sequence Data, Autosomal Dominant, Neurodegenerative disorder, and Paediatrics and reproductive medicine
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Technological improvements shifted sequencing from low-throughput, work-intensive, gel-based systems to high-throughput capillary systems. This resulted in a broad use of genomic resequencing to identify sequence variations in genes and... more
Technological improvements shifted sequencing from low-throughput, work-intensive, gel-based systems to high-throughput capillary systems. This resulted in a broad use of genomic resequencing to identify sequence variations in genes and regulatory, as well as extended genomic regions. We describe a software package, novoSNP, that conscientiously discovers single nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms (INDELs) in sequence trace files in a fast, reliable, and user-friendly way. We compared the performance of novoSNP with that of PolyPhred and PolyBayes on two data sets. The first data set comprised 1028 sequence trace files obtained from diagnostic mutation analyses of SCN1A (neuronal voltage-gated sodium channel α-subunit type I gene). The second data set comprised 9062 sequence trace files from a genomic resequencing project aiming at the construction of a high-density SNP map of MAPT (microtubule-associated protein tau gene). Visual inspection of these...
Research Interests: Genetics, Chemistry, Genomics, Polymorphism, Computational Biology, and 15 moreBiology, Medicine, Sequence Analysis, Biological Sciences, DNA, Humans, Animals, Genome, Single Nucleotide Polymorphism, Genetic Polymorphism, Genetic variation, Base Sequence, HUMAN MEDICINE, High density, and Medical and Health Sciences
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Aims:Prenatal stress has been associated with lifelong disturbances in stress response systems and with an increased vulnerability for psychiatric disorders. However, the effect of prenatal stress is at least partially determined by... more
Aims:Prenatal stress has been associated with lifelong disturbances in stress response systems and with an increased vulnerability for psychiatric disorders. However, the effect of prenatal stress is at least partially determined by individual genetic makeup. Recent data confim the potential role of the glucocorticoid receptor (GR) gene in modulating stress response and in the liability to develop mood disorders. In genetic association studies, single nucleotide polymorphisms (SNPs) in the GR gene were linked to variation in stress response systems (1). In a preliminary investigation, we studied 106 prepubertal children to estimate the impact of four GR gene polymorphisms on cortisol responses after a psychosocial stress test.Results:Carriers of the ER22/23EK mutation displayed significant lower cortisol responses to psychosocial stress compared to noncarriers. This particular polymorphism has earlier been associated to the vulnerability to develop MDD by our own research group (2) ...
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HPA axis dysfunction is a key neurobiological finding in major depression (MDD) and in a number of other stress related psychiatric disorders. Hyperdrive of corticotropin releasing hormone (CRH) is at the core of HPA axis dysregulation in... more
HPA axis dysfunction is a key neurobiological finding in major depression (MDD) and in a number of other stress related psychiatric disorders. Hyperdrive of corticotropin releasing hormone (CRH) is at the core of HPA axis dysregulation in MDD. The liability to develop CRH hyperdrive is a complex trait, partially determined by genetic factors. A main functional candidate gene for the regulation of the HPA axis is the gene encoding for the glucocorticoid receptor (GR). Transgenic mice with functional GR gene impairment show profound behavioral changes and elevated plasma corticotropin responses to stress. In humans, several GR polymorphisms were shown to influence HPA axis function. Recently, our group published a positive association finding between polymorphisms in the 5' region of the GR gene and recurrent MDD in two separate populations [1]. The action of the glucocorticoid receptor is tightly regulated by a number of co-chaperones. Binder et al. [2] found significant associations of response to antidepressants and polymorphisms in the FKBP5 gene, a glucocorticoid receptor−regulating co-chaperone of hsp-90. Several other candidate genes are of interest, such as the CRH receptor 1 and CRH receptor 2 genes, the CRH binding protein gene [3], the AVP receptor gene and the mineralocorticoid receptor gene. These and other genetic determinants of HPA axis function, from our own studies and from the literature, will be discussed.
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We report here a case-control association study with T102C polymorphism in the serotonin 2A receptor gene (HTR2A) in patients affected by unipolar affective disorder (UPAD) and in controls. A total of 284 subjects were genotyped (142 UPAD... more
We report here a case-control association study with T102C polymorphism in the serotonin 2A receptor gene (HTR2A) in patients affected by unipolar affective disorder (UPAD) and in controls. A total of 284 subjects were genotyped (142 UPAD and 142 controls). All subjects were interviewed using standard diagnostic interviews and matched. A homogenous population of unipolar patients with suicidal attempt was identified. Conditional logistic regression was applied. No association of the HTR2A polymorphism was found in the overall sample of 142 UPAD-control pairs regarding allele and genotype frequencies (P=0.36 and P=0.52 respectively) and homo-heterozygote distributions (P=0.91). This study confirms, in a multicentric European sample, the earlier observations that the T102C HTR2A polymorphism is not associated with UPAD. Nevertheless, a type 2 statistical error cannot be excluded. Therefore, to exclude the implication of HTR2A in UPAD, this result must be replicated in larger samples and in other populations using the transmission disequilibrium test and different polymorphisms around HTR2A.
Research Interests: Polymorphism, Medicine, Association study, Humans, Internal Medicine, and 15 moreEurope, Confidence intervals, Depressive Disorder, Disequilibrium, European, Mood Disorders, Genotype, Odds ratio, Genetic Polymorphism, Chi Square Distribution, Logistic Models, Affective Disorder, Case Control Studies, Gene frequency, and Medical and Health Sciences
Research Interests: Psychology, Polymorphism, Medicine, Belgium, Humans, and 15 moreFemale, Male, Depressive Disorder, Gene, Middle Aged, Gene Polymorphism, Genotype, Adult, Neurotrophic Factors, Affective Disorder, Haplotype, Case Control Studies, Psychology and Cognitive Sciences, Gene frequency, and Medical and Health Sciences
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Research Interests: Cognitive Science, Pediatrics, Magnetic Resonance Imaging, Epilepsy, Electroencephalography, and 15 moreMedicine, Humans, Genetic Testing, Mutation, Female, Male, Infant, Epilepsia, Clinical Sciences, Newborn Infant, Valproic Acid, Carbamazepine, X ray Computed Tomography, Neurosciences, and DNA mutational analysis
Page 1. Current Pharmacogenomics, 2006, 4, 191-208 191 1570-1603/06 $50.00+.00 ©2006 Bentham Science Publishers Ltd. Pharmacogenetics in Affective Disorders: A Drug Response Approach Robin Lefebvre and Jurgen Del-Favero* ...
