JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p?=?1.25×10(-8)), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genome-wide significant associations with hyperopia. These regions overlapped with loci on 15q14 (minimum p value?=?9.11×10(-11)) and 8q12 (minimum p value 1.82×10(-11)) previously reported for MSE and myopia age at onset. We also used an intermarker linkage- disequilibrium-based method for calculating the effective number of tests in targeted regional replication analyses. We analyzed myopia (which represents the closest phenotype in our data to the one used by Kiefer et al.) and showed replication of 10 additional loci associated with myopia previously reported by Kiefer et al. This is the first replication of these loci using myopia as the trait under analysis. "Replication-level" association was also seen between hyperopia and 12 of Kiefer et al.'s published loci. For the loci that show evidence of association to both myopia and hyperopia, the estimated effect of the risk alleles were in opposite directions for the two traits. This suggests that these loci are important contributors to variation of refractive error across the distribution.
Related JoVE Video
Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.
Ching-Yu Cheng, Maria Schache, M Kamran Ikram, Terri L Young, Jeremy A Guggenheim, Veronique Vitart, Stuart MacGregor, Virginie J M Verhoeven, Veluchamy A Barathi, Jiemin Liao, Pirro G Hysi, Joan E Bailey-Wilson, Beate St Pourcain, John P Kemp, George McMahon, Nicholas J Timpson, David M Evans, Grant W Montgomery, Aniket Mishra, Ya Xing Wang, Jie Jin Wang, Elena Rochtchina, Ozren Polašek, Alan F Wright, Najaf Amin, Elisabeth M van Leeuwen, James F Wilson, Craig E Pennell, Cornelia M van Duijn, Paulus T V M de Jong, Johannes R Vingerling, Xin Zhou, Peng Chen, Ruoying Li, Wan-Ting Tay, Yingfeng Zheng, Merwyn Chew, , Kathryn P Burdon, Jamie E Craig, Sudha K Iyengar, Robert P Igo, Jonathan H Lass, Emily Y Chew, Toomas Haller, Evelin Mihailov, Andres Metspalu, Juho Wedenoja, Claire L Simpson, Robert Wojciechowski, René Höhn, Alireza Mirshahi, Tanja Zeller, Norbert Pfeiffer, Karl J Lackner, Thomas Bettecken, Thomas Meitinger, Konrad Oexle, Mario Pirastu, Laura Portas, Abhishek Nag, Katie M Williams, Ekaterina Yonova-Doing, Ronald Klein, Barbara E Klein, S Mohsen Hosseini, Andrew D Paterson, Kari-Matti Mäkelä, Terho Lehtimäki, Mika Kähönen, Olli Raitakari, Nagahisa Yoshimura, Fumihiko Matsuda, Li Jia Chen, Chi Pui Pang, Shea Ping Yip, Maurice K H Yap, Akira Meguro, Nobuhisa Mizuki, Hidetoshi Inoko, Paul J Foster, Jing Hua Zhao, Eranga Vithana, E-Shyong Tai, Qiao Fan, Liang Xu, Harry Campbell, Brian Fleck, Igor Rudan, Tin Aung, Albert Hofman, André G Uitterlinden, Goran Bencic, Chiea-Chuen Khor, Hannah Forward, Olavi Pärssinen, Paul Mitchell, Fernando Rivadeneira, Alex W Hewitt, Cathy Williams, Ben A Oostra, Yik-Ying Teo, Christopher J Hammond, Dwight Stambolian, David A Mackey, Caroline C W Klaver, Tien-Yin Wong, Seang-Mei Saw, Paul N Baird.
Am. J. Hum. Genet.
PUBLISHED: 03-15-2013
Show Abstract
Hide Abstract
Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.
Related JoVE Video
Meta-analysis of genome-wide association studies in five cohorts reveals common variants in RBFOX1, a regulator of tissue-specific splicing, associated with refractive error.
Hum. Mol. Genet.
PUBLISHED: 03-07-2013
Show Abstract
Hide Abstract
Visual refractive errors (REs) are complex genetic traits with a largely unknown etiology. To date, genome-wide association studies (GWASs) of moderate size have identified several novel risk markers for RE, measured here as mean spherical equivalent (MSE). We performed a GWAS using a total of 7280 samples from five cohorts: the Age-Related Eye Disease Study (AREDS); the KORA study (Cooperative Health Research in the Region of Augsburg); the Framingham Eye Study (FES); the Ogliastra Genetic Park-Talana (OGP-Talana) Study and the Multiethnic Study of Atherosclerosis (MESA). Genotyping was performed on Illumina and Affymetrix platforms with additional markers imputed to the HapMap II reference panel. We identified a new genome-wide significant locus on chromosome 16 (rs10500355, P = 3.9 × 10(-9)) in a combined discovery and replication set (26 953 samples). This single nucleotide polymorphism (SNP) is located within the RBFOX1 gene which is a neuron-specific splicing factor regulating a wide range of alternative splicing events implicated in neuronal development and maturation, including transcription factors, other splicing factors and synaptic proteins.
Related JoVE Video
Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.
, S Hong Lee, Stephan Ripke, Benjamin M Neale, Stephen V Faraone, Shaun M Purcell, Roy H Perlis, Bryan J Mowry, Anita Thapar, Michael E Goddard, John S Witte, Devin Absher, Ingrid Agartz, Huda Akil, Farooq Amin, Ole A Andreassen, Adebayo Anjorin, Richard Anney, Verneri Anttila, Dan E Arking, Philip Asherson, Maria H Azevedo, Lena Backlund, Judith A Badner, Anthony J Bailey, Tobias Banaschewski, Jack D Barchas, Michael R Barnes, Thomas B Barrett, Nicholas Bass, Agatino Battaglia, Michael Bauer, Mònica Bayés, Frank Bellivier, Sarah E Bergen, Wade Berrettini, Catalina Betancur, Thomas Bettecken, Joseph Biederman, Elisabeth B Binder, Donald W Black, Douglas H R Blackwood, Cinnamon S Bloss, Michael Boehnke, Dorret I Boomsma, Gerome Breen, René Breuer, Richard Bruggeman, Paul Cormican, Nancy G Buccola, Jan K Buitelaar, William E Bunney, Joseph D Buxbaum, William F Byerley, Enda M Byrne, Sian Caesar, Wiepke Cahn, Rita M Cantor, Miguel Casas, Aravinda Chakravarti, Kimberly Chambert, Khalid Choudhury, Sven Cichon, C Robert Cloninger, David A Collier, Edwin H Cook, Hilary Coon, Bru Cormand, Aiden Corvin, William H Coryell, David W Craig, Ian W Craig, Jennifer Crosbie, Michael L Cuccaro, David Curtis, Darina Czamara, Susmita Datta, Geraldine Dawson, Richard Day, Eco J De Geus, Franziska Degenhardt, Srdjan Djurovic, Gary J Donohoe, Alysa E Doyle, Jubao Duan, Frank Dudbridge, Eftichia Duketis, Richard P Ebstein, Howard J Edenberg, Josephine Elia, Sean Ennis, Bruno Etain, Ayman Fanous, Anne E Farmer, I Nicol Ferrier, Matthew Flickinger, Eric Fombonne, Tatiana Foroud, Josef Frank, Barbara Franke, Christine Fraser, Robert Freedman, Nelson B Freimer, Christine M Freitag, Marion Friedl, Louise Frisén, Louise Gallagher, Pablo V Gejman, Lyudmila Georgieva, Elliot S Gershon, Daniel H Geschwind, Ina Giegling, Michael Gill, Scott D Gordon, Katherine Gordon-Smith, Elaine K Green, Tiffany A Greenwood, Dorothy E Grice, Magdalena Gross, Detelina Grozeva, Weihua Guan, Hugh Gurling, Lieuwe de Haan, Jonathan L Haines, Hakon Hakonarson, Joachim Hallmayer, Steven P Hamilton, Marian L Hamshere, Thomas F Hansen, Annette M Hartmann, Martin Hautzinger, Andrew C Heath, Anjali K Henders, Stefan Herms, Ian B Hickie, Maria Hipolito, Susanne Hoefels, Peter A Holmans, Florian Holsboer, Witte J Hoogendijk, Jouke-Jan Hottenga, Christina M Hultman, Vanessa Hus, Andrés Ingason, Marcus Ising, Stéphane Jamain, Edward G Jones, Ian Jones, Lisa Jones, Jung-Ying Tzeng, Anna K Kähler, René S Kahn, Radhika Kandaswamy, Matthew C Keller, James L Kennedy, Elaine Kenny, Lindsey Kent, Yunjung Kim, George K Kirov, Sabine M Klauck, Lambertus Klei, James A Knowles, Martin A Kohli, Daniel L Koller, Bettina Konte, Ania Korszun, Lydia Krabbendam, Robert Krasucki, Jonna Kuntsi, Phoenix Kwan, Mikael Landén, Niklas Långström, Mark Lathrop, Jacob Lawrence, William B Lawson, Marion Leboyer, David H Ledbetter, Phil H Lee, Todd Lencz, Klaus-Peter Lesch, Douglas F Levinson, Cathryn M Lewis, Jun Li, Paul Lichtenstein, Jeffrey A Lieberman, Dan-Yu Lin, Don H Linszen, Chunyu Liu, Falk W Lohoff, Sandra K Loo, Catherine Lord, Jennifer K Lowe, Susanne Lucae, Donald J MacIntyre, Pamela A F Madden, Elena Maestrini, Patrik K E Magnusson, Pamela B Mahon, Wolfgang Maier, Anil K Malhotra, Shrikant M Mane, Christa L Martin, Nicholas G Martin, Manuel Mattheisen, Keith Matthews, Morten Mattingsdal, Steven A McCarroll, Kevin A McGhee, James J McGough, Patrick J McGrath, Peter McGuffin, Melvin G McInnis, Andrew McIntosh, Rebecca McKinney, Alan W McLean, Francis J McMahon, William M McMahon, Andrew McQuillin, Helena Medeiros, Sarah E Medland, Sandra Meier, Ingrid Melle, Fan Meng, Jobst Meyer, Christel M Middeldorp, Lefkos Middleton, Vihra Milanova, Ana Miranda, Anthony P Monaco, Grant W Montgomery, Jennifer L Moran, Daniel Moreno-De-Luca, Gunnar Morken, Derek W Morris, Eric M Morrow, Valentina Moskvina, Pierandrea Muglia, Thomas W Mühleisen, Walter J Muir, Bertram Müller-Myhsok, Michael Murtha, Richard M Myers, Inez Myin-Germeys, Michael C Neale, Stan F Nelson, Caroline M Nievergelt, Ivan Nikolov, Vishwajit Nimgaonkar, Willem A Nolen, Markus M Nöthen, John I Nurnberger, Evaristus A Nwulia, Dale R Nyholt, Colm O'Dushlaine, Robert D Oades, Ann Olincy, Guiomar Oliveira, Line Olsen, Roel A Ophoff, Urban Osby, Michael J Owen, Aarno Palotie, Jeremy R Parr, Andrew D Paterson, Carlos N Pato, Michele T Pato, Brenda W Penninx, Michele L Pergadia, Margaret A Pericak-Vance, Benjamin S Pickard, Jonathan Pimm, Joseph Piven, Danielle Posthuma, James B Potash, Fritz Poustka, Peter Propping, Vinay Puri, Digby J Quested, Emma M Quinn, Josep Antoni Ramos-Quiroga, Henrik B Rasmussen, Soumya Raychaudhuri, Karola Rehnström, Andreas Reif, Marta Ribasés, John P Rice, Marcella Rietschel, Kathryn Roeder, Herbert Roeyers, Lizzy Rossin, Aribert Rothenberger, Guy Rouleau, Douglas Ruderfer, Dan Rujescu, Alan R Sanders, Stephan J Sanders, Susan L Santangelo, Joseph A Sergeant, Russell Schachar, Martin Schalling, Alan F Schatzberg, William A Scheftner, Gerard D Schellenberg, Stephen W Scherer, Nicholas J Schork, Thomas G Schulze, Johannes Schumacher, Markus Schwarz, Edward Scolnick, Laura J Scott, Jianxin Shi, Paul D Shilling, Stanley I Shyn, Jeremy M Silverman, Susan L Slager, Susan L Smalley, Johannes H Smit, Erin N Smith, Edmund J S Sonuga-Barke, David St Clair, Matthew State, Michael Steffens, Hans-Christoph Steinhausen, John S Strauss, Jana Strohmaier, T Scott Stroup, James S Sutcliffe, Peter Szatmari, Szabocls Szelinger, Srinivasa Thirumalai, Robert C Thompson, Alexandre A Todorov, Federica Tozzi, Jens Treutlein, Manfred Uhr, Edwin J C G van den Oord, Gerard van Grootheest, Jim van Os, Astrid M Vicente, Veronica J Vieland, John B Vincent, Peter M Visscher, Christopher A Walsh, Thomas H Wassink, Stanley J Watson, Myrna M Weissman, Thomas Werge, Thomas F Wienker, Ellen M Wijsman, Gonneke Willemsen, Nigel Williams, A Jeremy Willsey, Stephanie H Witt, Wei Xu, Allan H Young, Timothy W Yu, Stanley Zammit, Peter P Zandi, Peng Zhang, Frans G Zitman, Sebastian Zöllner, Bernie Devlin, John R Kelsoe, Pamela Sklar, Mark J Daly, Michael C O'Donovan, Nicholas Craddock, Patrick F Sullivan, Jordan W Smoller, Kenneth S Kendler, Naomi R Wray.
Nat. Genet.
PUBLISHED: 02-10-2013
Show Abstract
Hide Abstract
Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohns disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Related JoVE Video
Nucleosome positioning patterns derived from human apoptotic nucleosomes.
J. Biomol. Struct. Dyn.
PUBLISHED: 11-10-2011
Show Abstract
Hide Abstract
This communication reports on the nucleosome positioning patterns (bendability matrices) for the human genome, derived from over 8_million nucleosome DNA sequences obtained from apoptotically digested lymphocytes. This digestion procedure is used here for the first time for the purpose of extraction and sequencing of the nucleosome DNA fragments. The dominant motifs suggested by the matrices of DNA bendability calculated for light and heavy isochores are significantly different. Both, however, are in full agreement with the linear description YRRRRRYYYYYR, and with earlier derivations by N-gram extensions. Thus, the choice of the nucleosome positioning patterns crucially depends on the G + C composition of the analyzed sequences.
Related JoVE Video
Human nucleosomes: special role of CG dinucleotides and Alu-nucleosomes.
BMC Genomics
PUBLISHED: 05-31-2011
Show Abstract
Hide Abstract
The periodical occurrence of dinucleotides with a period of 10.4 bases now is undeniably a hallmark of nucleosome positioning. Whereas many eukaryotic genomes contain visible and even strong signals for periodic distribution of dinucleotides, the human genome is rather featureless in this respect. The exact sequence features in the human genome that govern the nucleosome positioning remain largely unknown.
Related JoVE Video
Nucleosome DNA sequence structure of isochores.
BMC Genomics
PUBLISHED: 04-21-2011
Show Abstract
Hide Abstract
Significant differences in G+C content between different isochore types suggest that the nucleosome positioning patterns in DNA of the isochores should be different as well.
Related JoVE Video
The neuronal transporter gene SLC6A15 confers risk to major depression.
Neuron
PUBLISHED: 03-18-2011
Show Abstract
Hide Abstract
Major depression (MD) is one of the most prevalent psychiatric disorders and a leading cause of loss in work productivity. A combination of genetic and environmental risk factors probably contributes to MD. We present data from a genome-wide association study revealing a neuron-specific neutral amino acid transporter (SLC6A15) as a susceptibility gene for MD. Risk allele carrier status in humans and chronic stress in mice were associated with a downregulation of the expression of this gene in the hippocampus, a brain region implicated in the pathophysiology of MD. The same polymorphisms also showed associations with alterations in hippocampal volume and neuronal integrity. Thus, decreased SLC6A15 expression, due to genetic or environmental factors, might alter neuronal circuits related to the susceptibility for MD. Our convergent data from human genetics, expression studies, brain imaging, and animal models suggest a pathophysiological mechanism for MD that may be accessible to drug targeting.
Related JoVE Video
SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype.
Nat. Genet.
PUBLISHED: 01-16-2011
Show Abstract
Hide Abstract
DNA interstrand crosslink repair requires several classes of proteins, including structure-specific endonucleases and Fanconi anemia proteins. SLX4, which coordinates three separate endonucleases, was recently recognized as an important regulator of DNA repair. Here we report the first human individuals found to have biallelic mutations in SLX4. These individuals, who were previously diagnosed as having Fanconi anemia, add SLX4 as an essential component to the FA-BRCA genome maintenance pathway.
Related JoVE Video
Evidence for VAV2 and ZNF433 as susceptibility genes for multiple sclerosis.
J. Neuroimmunol.
PUBLISHED: 06-01-2010
Show Abstract
Hide Abstract
In a genome wide association study consisting of 592 German multiple sclerosis (MS) patients and 825 controls we were able to replicate the association of the HLA region with MS independently of previous case control studies. No SNPs outside the HLA region reached a genome wide level of significance. Nevertheless, we found suggestive evidence for an association of MS with variants in two new genes, the VAV2 gene and the gene for ZNF433.
Related JoVE Video
A genomewide association study points to multiple loci that predict antidepressant drug treatment outcome in depression.
Arch. Gen. Psychiatry
PUBLISHED: 09-09-2009
Show Abstract
Hide Abstract
The efficacy of antidepressant drug treatment in depression is unsatisfactory; 1 in 3 patients does not fully recover even after several treatment trials. Genetic factors and clinical characteristics contribute to the failure of a favorable treatment outcome.
Related JoVE Video
Repertoires of the nucleosome-positioning dinucleotides.
PLoS ONE
PUBLISHED: 06-01-2009
Show Abstract
Hide Abstract
It is generally accepted that the organization of eukaryotic DNA into chromatin is strongly governed by a code inherent in the genomic DNA sequence. This code, as well as other codes, is superposed on the triplets coding for amino acids. The history of the chromatin code started three decades ago with the discovery of the periodic appearance of certain dinucleotides, with AA/TT and RR/YY giving the strongest signals, all with a period of 10.4 bases. Every base-pair stack in the DNA duplex has specific deformation properties, thus favoring DNA bending in a specific direction. The appearance of the corresponding dinucleotide at the distance 10.4 xn bases will facilitate DNA bending in that direction, which corresponds to the minimum energy of DNA folding in the nucleosome. We have analyzed the periodic appearances of all 16 dinucleotides in the genomes of thirteen different eukaryotic organisms. Our data show that a large variety of dinucleotides (if not all) are, apparently, contributing to the nucleosome positioning code. The choice of the periodical dinucleotides differs considerably from one organism to another. Among other 10.4 base periodicities, a strong and very regular 10.4 base signal was observed for CG dinucleotides in the genome of the honey bee A. mellifera. Also, the dinucleotide CG appears as the only periodical component in the human genome. This observation seems especially relevant since CpG methylation is well known to modulate chromatin packing and regularity. Thus, the selection of the dinucleotides contributing to the chromatin code is species specific, and may differ from region to region, depending on the sequence context.
Related JoVE Video
Age-related macular degeneration and functional promoter and coding variants of the apolipoprotein E gene.
Hum. Mutat.
PUBLISHED: 04-23-2009
Show Abstract
Hide Abstract
Age-related macular degeneration (AMD) is a frequent, multifactorial disease of the central retina and a major cause of irreversible vision loss in industrialized countries. Apolipoprotein E (APOE) has been consistently associated with AMD, particularly its two functional isoforms E2 (predisposing) and E4 (protective). The biological correlate of this association, however, is still unclear. In this study, we have defined an extended haplotype block encompassing the entire APOE gene locus, including known coding as well as cis-regulatory promoter variants. Of the five extended APOE haplotypes common in the general population, two were found to be significantly associated with AMD, namely G-G-G-G-epsilon2 (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.19-2.12) and T-G-A-G-epsilon4 (OR, 0.76; 95% CI, 0.58-0.99). When analyzing common extended haplotype combinations, T-C-G-G-epsilon3/T-G-A-G-epsilon4 exhibited the most prominent effect (OR, 0.32; 95% CI, 0.20-0.51). Intriguingly, we also found one extended epsilon3-haplotype, G-G-G-A-epsilon3, to be protective in the homozygous state (OR, 0.65; 95% CI, 0.49-0.87). Since single nucleotide polymorphism (SNP) rs405509:G>T is a constituent of the extended epsilon-haplotype block and is known to significantly influence APOE promoter activity, we hypothesize that both the relative rate of APOE isoform expression in conjunction with established functional differences of the respective isoforms may be crucial in mediating AMD pathology. This would also imply that genotyping of the core epsilon-haplotypes alone is not sufficient to estimate AMD risk, but that determination of extended haplotype combinations, including the functional promoter SNP rs405509, is required instead.
Related JoVE Video
Polymorphisms in the angiotensin-converting enzyme gene region predict coping styles in healthy adults and depressed patients.
Am. J. Med. Genet. B Neuropsychiatr. Genet.
PUBLISHED: 03-11-2009
Show Abstract
Hide Abstract
Dispositional coping styles are important moderators of the stress reaction and are altered in stress-related disorders like cardiovascular diseases and affective disorders. Heritability studies suggest a considerable genetic contribution to the interindividual variability in coping styles. Since the angiotensin-converting enzyme (ACE) gene has been described to be associated with the vulnerability for stress-related disorders and with altered stress hormone regulation, we investigated the ACE gene as potential candidate gene for coping styles. Five hundred forty one mentally healthy subjects and 194 patients suffering from depression participating in the Munich Antidepressant Response Signature (MARS) project were examined. Coping styles were assessed with a self-report questionnaire (German Stress Coping Questionnaire SVF78) measuring the individual coping style pattern in response to stressful situations. We genotyped 15 single nucleotide polymorphisms (SNPs) and the insertion/Deletion (I/D)-polymorphism in the ACE gene region and investigated their associations with coping styles. In healthy subjects, the highest association was observed between rs8066276, an intronic SNP of the ACE gene, and the coping factor Distraction. A further intronic SNP rs4305, not in linkage disequilibrium with rs8066276, showed an association with Devaluation/Defense. All associated copying styles can be categorized as potentially stress reducing factors (positive coping). Both SNPs were also found to be associated with positive coping styles in the patient sample; rs8066276 was associated with Devaluation/Defense, and rs4305 showed associations with Control. These results suggest that the ACE gene is involved in the development of coping strategies.
Related JoVE Video
A hypomorphic vasopressin allele prevents anxiety-related behavior.
PLoS ONE
PUBLISHED: 01-10-2009
Show Abstract
Hide Abstract
To investigate neurobiological correlates of trait anxiety, CD1 mice were selectively bred for extremes in anxiety-related behavior, with high (HAB) and low (LAB) anxiety-related behavior mice additionally differing in behavioral tests reflecting depression-like behavior.
Related JoVE Video
Genotyping of fanconi anemia patients by whole exome sequencing: advantages and challenges.
PLoS ONE
Show Abstract
Hide Abstract
Fanconi anemia (FA) is a rare genomic instability syndrome. Disease-causing are biallelic mutations in any one of at least 15 genes encoding members of the FA/BRCA pathway of DNA-interstrand crosslink repair. Patients are diagnosed based upon phenotypical manifestations and the diagnosis of FA is confirmed by the hypersensitivity of cells to DNA interstrand crosslinking agents. Customary molecular diagnostics has become increasingly cumbersome, time-consuming and expensive the more FA genes have been identified. We performed Whole Exome Sequencing (WES) in four FA patients in order to investigate the potential of this method for FA genotyping. In search of an optimal WES methodology we explored different enrichment and sequencing techniques. In each case we were able to identify the pathogenic mutations so that WES provided both, complementation group assignment and mutation detection in a single approach. The mutations included homozygous and heterozygous single base pair substitutions and a two-base-pair duplication in FANCJ, -D1, or -D2. Different WES strategies had no critical influence on the individual outcome. However, database errors and in particular pseudogenes impose obstacles that may prevent correct data perception and interpretation, and thus cause pitfalls. With these difficulties in mind, our results show that WES is a valuable tool for the molecular diagnosis of FA and a sufficiently safe technique, capable of engaging increasingly in competition with classical genetic approaches.
Related JoVE Video
The endocrine stress response is linked to one specific locus on chromosome 3 in a mouse model based on extremes in trait anxiety.
BMC Genomics
Show Abstract
Hide Abstract
The hypothalamic-pituitary-adrenal (HPA) axis is essential to control physiological stress responses in mammals. Its dysfunction is related to several mental disorders, including anxiety and depression. The aim of this study was to identify genetic loci underlying the endocrine regulation of the HPA axis.
Related JoVE Video
Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels.
Eur Neuropsychopharmacol
Show Abstract
Hide Abstract
Leptin, a peptide hormone from adipose tissue and key player in weight regulation, has been suggested to be involved in sleep and cognition and to exert antidepressant-like effects, presumably via its action on the HPA-axis and hippocampal function. This led us to investigate whether genetic variants in the leptin gene, the level of leptin mRNA-expression and leptin serum concentrations are associated with response to antidepressant treatment. Our sample consisted of inpatients from the Munich Antidepressant Response Signature (MARS) project with weekly Hamilton Depression ratings, divided into two subsamples. In the exploratory sample (n=251) 17 single nucleotide polymorphisms (SNPs) covering the leptin gene region were genotyped. We found significant associations of several SNPs with impaired antidepressant treatment outcome and impaired cognitive performance after correction for multiple testing. The SNP (rs10487506) showing the highest association with treatment response (p=3.9×10(-5)) was analyzed in the replication sample (n=358) and the association could be verified (p=0.021) with response to tricyclic antidepressants. In an additional meta-analysis combining results from the MARS study with data from the Genome-based Therapeutic Drugs for Depression (GENDEP) and the Sequenced Treatment Alternatives to Relieve Depression (STAR(?)D) studies, nominal associations of several polymorphisms in the upstream vicinity of rs10487506 with treatment outcome were detected (p=0.001). In addition, we determined leptin mRNA expression in lymphocytes and leptin serum levels in subsamples of the MARS study. Unfavorable treatment outcome was accompanied with decreased leptin mRNA and leptin serum levels. Our results suggest an involvement of leptin in antidepressant action and cognitive function in depression with genetic polymorphisms in the leptin gene, decreased leptin gene expression and leptin deficiency in serum being risk factors for resistance to antidepressant therapy in depressed patients.
Related JoVE Video
Apoptotic cleavage of DNA in human lymphocyte chromatin shows high sequence specificity.
J. Biomol. Struct. Dyn.
Show Abstract
Hide Abstract
Apoptotic digestion of human lymphocyte chromatin results in the appearance of large amounts of nucleosome size DNA fragments. Sequencing of these fragments and analysis of the distribution of bases around the apoptotic nucleases cutting sites revealed a rather strong consensus sequence, not observed earlier. The consensus TAAAgTAcTTTA is characterized by complementary symmetry, resembling prokaryotic restriction sites. This consensus also possesses three TA dinucleotide steps, separated by five bases (corresponding to a half-period of the DNA double helix), suggesting strong bending of the DNA at the cut sites which is perhaps required for cutting.
Related JoVE Video
Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium.
Virginie J M Verhoeven, Pirro G Hysi, Seang-Mei Saw, Veronique Vitart, Alireza Mirshahi, Jeremy A Guggenheim, Mary Frances Cotch, Kenji Yamashiro, Paul N Baird, David A Mackey, Robert Wojciechowski, M Kamran Ikram, Alex W Hewitt, Priya Duggal, Sarayut Janmahasatian, Chiea-Chuen Khor, Qiao Fan, Xin Zhou, Terri L Young, E-Shyong Tai, Liang-Kee Goh, Yi-Ju Li, Tin Aung, Eranga Vithana, Yik-Ying Teo, Wanting Tay, Xueling Sim, Igor Rudan, Caroline Hayward, Alan F Wright, Ozren Polašek, Harry Campbell, James F Wilson, Brian W Fleck, Isao Nakata, Nagahisa Yoshimura, Ryo Yamada, Fumihiko Matsuda, Kyoko Ohno-Matsui, Abhishek Nag, George McMahon, Beate St Pourcain, Yi Lu, Jugnoo S Rahi, Phillippa M Cumberland, Shomi Bhattacharya, Claire L Simpson, Larry D Atwood, Xiaohui Li, Leslie J Raffel, Federico Murgia, Laura Portas, Dominiek D G Despriet, Leonieke M E van Koolwijk, Christian Wolfram, Karl J Lackner, Anke Tönjes, Reedik Mägi, Terho Lehtimäki, Mika Kähönen, Tonu Esko, Andres Metspalu, Taina Rantanen, Olavi Pärssinen, Barbara E Klein, Thomas Meitinger, Timothy D Spector, Ben A Oostra, Albert V Smith, Paulus T V M de Jong, Albert Hofman, Najaf Amin, Lennart C Karssen, Fernando Rivadeneira, Johannes R Vingerling, Guðný Eiríksdóttir, Vilmundur Gudnason, Angela Döring, Thomas Bettecken, André G Uitterlinden, Cathy Williams, Tanja Zeller, Raphaele Castagné, Konrad Oexle, Cornelia M van Duijn, Sudha K Iyengar, Paul Mitchell, Jie Jin Wang, René Höhn, Norbert Pfeiffer, Joan E Bailey-Wilson, Dwight Stambolian, Tien-Yin Wong, Christopher J Hammond, Caroline C W Klaver.
Hum. Genet.
Show Abstract
Hide Abstract
Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 × 10(-12) for SNP rs634990 in Caucasians, and 9.65 × 10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 × 10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 × 10(-2) for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.
Related JoVE Video
A mega-analysis of genome-wide association studies for major depressive disorder.
, Stephan Ripke, Naomi R Wray, Cathryn M Lewis, Steven P Hamilton, Myrna M Weissman, Gerome Breen, Enda M Byrne, Douglas H R Blackwood, Dorret I Boomsma, Sven Cichon, Andrew C Heath, Florian Holsboer, Susanne Lucae, Pamela A F Madden, Nicholas G Martin, Peter McGuffin, Pierandrea Muglia, Markus M Noethen, Brenda P Penninx, Michele L Pergadia, James B Potash, Marcella Rietschel, Danyu Lin, Bertram Müller-Myhsok, Jianxin Shi, Stacy Steinberg, Hans J Grabe, Paul Lichtenstein, Patrik Magnusson, Roy H Perlis, Martin Preisig, Jordan W Smoller, Kari Stefansson, Rudolf Uher, Zoltan Kutalik, Katherine E Tansey, Alexander Teumer, Alexander Viktorin, Michael R Barnes, Thomas Bettecken, Elisabeth B Binder, René Breuer, Victor M Castro, Susanne E Churchill, William H Coryell, Nick Craddock, Ian W Craig, Darina Czamara, Eco J De Geus, Franziska Degenhardt, Anne E Farmer, Maurizio Fava, Josef Frank, Vivian S Gainer, Patience J Gallagher, Scott D Gordon, Sergey Goryachev, Magdalena Gross, Michel Guipponi, Anjali K Henders, Stefan Herms, Ian B Hickie, Susanne Hoefels, Witte Hoogendijk, Jouke Jan Hottenga, Dan V Iosifescu, Marcus Ising, Ian Jones, Lisa Jones, Tzeng Jung-Ying, James A Knowles, Isaac S Kohane, Martin A Kohli, Ania Korszun, Mikael Landén, William B Lawson, Glyn Lewis, Donald Macintyre, Wolfgang Maier, Manuel Mattheisen, Patrick J McGrath, Andrew McIntosh, Alan McLean, Christel M Middeldorp, Lefkos Middleton, Grant M Montgomery, Shawn N Murphy, Matthias Nauck, Willem A Nolen, Dale R Nyholt, Michael O'Donovan, Högni Oskarsson, Nancy Pedersen, William A Scheftner, Andrea Schulz, Thomas G Schulze, Stanley I Shyn, Engilbert Sigurdsson, Susan L Slager, Johannes H Smit, Hreinn Stefansson, Michael Steffens, Thorgeir Thorgeirsson, Federica Tozzi, Jens Treutlein, Manfred Uhr, Edwin J C G van den Oord, Gerard van Grootheest, Henry Völzke, Jeffrey B Weilburg, Gonneke Willemsen, Frans G Zitman, Benjamin Neale, Mark Daly, Douglas F Levinson, Patrick F Sullivan.
Mol. Psychiatry
Show Abstract
Hide Abstract
Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18?759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50?695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10(-8)), and all were in a 248?kb interval of high LD on 3p21.1 (chr3:52?425?083-53?822?102, minimum P=5.9 × 10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.