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See detailThe genome of cyprinid herpesvirus 3 encodes 40 proteins incorporated in mature virions
Michel, Benjamin ULg; Leroy, B.; Victor, Stalinraj ULg et al

in Journal of General Virology (The) (2010)

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See detailA genome scan conducted in a multigenerational pedigree with convergent strabismus supports a complex genetic determinism.
GEORGES, Anouk ULg; Cambisano, Nadine ULg; Ahariz, Naïma ULg et al

in PloS one (2013), 8(12), 83574

A genome-wide linkage scan was conducted in a Northern-European multigenerational pedigree with nine of 40 related members affected with concomitant strabismus. Twenty-seven members of the pedigree ... [more ▼]

A genome-wide linkage scan was conducted in a Northern-European multigenerational pedigree with nine of 40 related members affected with concomitant strabismus. Twenty-seven members of the pedigree including all affected individuals were genotyped using a SNP array interrogating > 300,000 common SNPs. We conducted parametric and non-parametric linkage analyses assuming segregation of an autosomal dominant mutation, yet allowing for incomplete penetrance and phenocopies. We detected two chromosome regions with near-suggestive evidence for linkage, respectively on chromosomes 8 and 18. The chromosome 8 linkage implied a penetrance of 0.80 and a rate of phenocopy of 0.11, while the chromosome 18 linkage implied a penetrance of 0.64 and a rate of phenocopy of 0. Our analysis excludes a simple genetic determinism of strabismus in this pedigree. [less ▲]

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See detailA genome scan for athletic performance in the thoroughbred.
Durkin, Keith ULg; Raudsepp, T; Skow, L.C. et al

Poster (2008, July)

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See detailGenome scan for familial abdominal aortic aneurysm using sex and family history as covariates suggests genetic heterogeneity and identifies linkage to chromosome 19q13.
Shibamura, Hidenori; Olson, Jane M; van Vlijmen-Van Keulen, Clarissa et al

in Circulation (2004), 109(17), 2103-8

BACKGROUND: Abdominal aortic aneurysm (AAA) is a relatively common disease, with 1% to 2% of the population harboring aneurysms. Genetic risk factors are likely to contribute to the development of AAAs ... [more ▼]

BACKGROUND: Abdominal aortic aneurysm (AAA) is a relatively common disease, with 1% to 2% of the population harboring aneurysms. Genetic risk factors are likely to contribute to the development of AAAs, although no such risk factors have been identified. METHODS AND RESULTS: We performed a whole-genome scan of AAA using affected-relative-pair (ARP) linkage analysis that includes covariates to allow for genetic heterogeneity. We found strong evidence of linkage (logarithm of odds [LOD] score=4.64) to a region near marker D19S433 at 51.88 centimorgans (cM) on chromosome 19 with 36 families (75 ARPs) when including sex and the number of affected first-degree relatives of the proband (N(aff)) as covariates. We then genotyped 83 additional families for the same markers and typed additional markers for all families and obtained a LOD score of 4.75 (P=0.00014) with sex, N(aff), and their interaction as covariates near marker D19S416 (58.69 cM). We also identified a region on chromosome 4 with a LOD score of 3.73 (P=0.0012) near marker D4S1644 using the same covariate model as for chromosome 19. CONCLUSIONS: Our results provide evidence for genetic heterogeneity and the presence of susceptibility loci for AAA on chromosomes 19q13 and 4q31. [less ▲]

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See detailGenome Sequence of the Edible Cyanobacterium Arthrospira sp. PCC 8005
Janssen, Paul; Morin, Nicolas; Mergeay, Max et al

in Journal of Bacteriology (2010), 192(9), 24652466

We determined the genome sequence of Arthrospira sp. PCC 8005, a cyanobacterial strain of great interest to the European Space Agency for its nutritive value and oxygenic properties in the Micro ... [more ▼]

We determined the genome sequence of Arthrospira sp. PCC 8005, a cyanobacterial strain of great interest to the European Space Agency for its nutritive value and oxygenic properties in the Micro-Ecological Life Support System Alternative (MELiSSA) biological life support system for long-term manned missions into space. [less ▲]

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See detailGenome wide scan in a Flemish inflammatory bowel disease population: support for the IBD4 locus, population heterogeneity, and epistasis
Vermeire, S.; Rutgeerts, P.; Van Steen, Kristel ULg et al

in Gut (2004), 53(7), 980-986

Background and aims: Genome wide scans in inflammatory bowel disease (IBD) have indicated various susceptibility regions with replication of 16cen (IBD1), 12q (IBD2), 6p (IBD3), 14q11 (IBD4), and 3p21. As ... [more ▼]

Background and aims: Genome wide scans in inflammatory bowel disease (IBD) have indicated various susceptibility regions with replication of 16cen (IBD1), 12q (IBD2), 6p (IBD3), 14q11 (IBD4), and 3p21. As no linkage was previously found on IBD regions 3, 7, 12, and 16 in Flemish IBD families, a genome wide scan was performed to detect other susceptibility regions in this population. Methods: A cohort of 149 IBD affected relative pairs, all recruited from the Northern Flemish part of Belgium, were genotyped using microsatellite markers at 12 cM intervals, and analysed by Genehunter non-parametric linkage software. All families were further genotyped for the three main Crohn's disease associated variants in the NOD2/CARD15 gene. Results: Nominal evidence for linkage was observed on chromosomes 1 (D1S197: multipoint nonparametric linkage (NPL) score 2.57, p = 0.004; and at D1S305-D1S252: NPL 2.97, p = 0.001), 4q (D4S406: NPL 1.95, p = 0.03), 6q16 (D6S314: NPL 2.44, p = 0.007), 10p12 (D10S197: NPL 2.05, p = 0.02), 11q22 (D11S35-D11S927: NPL 1.95, p = 0.02) 14q11-12 (D14S80: NPL 2.41, p = 0.008), 20p12 (D20S192: NPL 2.7, p = 0.003), and Xq (DXS990: NPL 1.70, p = 0.04). A total of 51.4% of patients carried at least one NOD2/CARD15 variant. Furthermore, epistasis was observed between susceptibility regions 6q/10p and 20p/10p. Conclusion: Genome scanning in a Flemish IBD population found nominal evidence for linkage on 1p, 4q, 10p12, and 14q11, overlapping with other genome scan results, with linkage on 14q11-12 supporting the IBD4 locus. The results further show that epistasis is contributing to the complex model of IBD and indicate that population heterogeneity is not to be underestimated. Finally, NOD2/CARD15 is clearly implicated in the Flemish IBD population. [less ▲]

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See detailGenome-wide analysis of the effect of heavy ions bombardment on gene expression and alternative splicing by neuronal cells.
Lambert, Charles ULg; Ernst, Eric; Quintens, R et al

Conference (2012, June 18)

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See detailGenome-wide association analysis identifies susceptibility loci for migraine without aura.
Freilinger, Tobias; Anttila, Verneri; de Vries, Boukje et al

in Nature Genetics (2012), 44(7), 777-82

Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this ... [more ▼]

Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 x 10(-5) for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 x 10(-4); combined P = 7.06 x 10(-11)) and at 3p24 (near TGFBR2; replication P = 1.0 x 10(-4); combined P = 1.17 x 10(-9)). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 x 10(-8) and P = 0.02; combined P = 3.86 x 10(-8), respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder. [less ▲]

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See detailGenome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease
Barrett, Jeffrey C.; Hansoul, Sarah ULg; Nicolae, Dan L. et al

in Nature Genetics (2008), 40(8), 955-62

Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total ... [more ▼]

Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls. The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development. [less ▲]

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See detailGenome-Wide Association Interaction Analysis for Alzheimer’s Disease
Gusareva, Elena ULg; Carrasquillo, Minerva M.; Bellenguez, Céline et al

in Neurobiology of Aging (2014)

We propose a minimal protocol for exhaustive genome-wide association interaction analysis that involves screening for epistasis over large-scale genomic data combining strengths of different methods and ... [more ▼]

We propose a minimal protocol for exhaustive genome-wide association interaction analysis that involves screening for epistasis over large-scale genomic data combining strengths of different methods and statistical tools. The different steps of this protocol are illustrated on a real-life data application for Alzheimer's disease (AD) (2259 patients and 6017 controls from France). Particularly, in the exhaustive genome-wide epistasis screening we identified AD-associated interacting SNPs-pair from chromosome 6q11.1 (rs6455128, the KHDRBS2 gene) and 13q12.11 (rs7989332, the CRYL1 gene) (p = 0.006, corrected for multiple testing). A replication analysis in the independent AD cohort from Germany (555 patients and 824 controls) confirmed the discovered epistasis signal (p = 0.036). This signal was also supported by a meta-analysis approach in 5 independent AD cohorts that was applied in the context of epistasis for the first time. Transcriptome analysis revealed negative correlation between expression levels of KHDRBS2 and CRYL1 in both the temporal cortex (β = -0.19, p = 0.0006) and cerebellum (β = -0.23, p < 0.0001) brain regions. This is the first time a replicable epistasis associated with AD was identified using a hypothesis free screening approach. [less ▲]

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See detailGenome-wide association interaction analysis for Alzheimer’s disease.
Gusareva, Elena ULg; Bellenguez, C; Cuyvers, E et al

Poster (2014, January 27)

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See detailGenome-wide association interaction analysis for Alzheimer’s disease.
Gusareva, Elena ULg; Bellenguez, C; Cuyvers, E et al

Poster (2013, October)

Identification of epistasis is a challenging task that when successful gives new clues to systems-level genetics where the complexity of underling biology of human disease can be better understood. Though ... [more ▼]

Identification of epistasis is a challenging task that when successful gives new clues to systems-level genetics where the complexity of underling biology of human disease can be better understood. Though many novel methods for detecting epistasis have been proposed and many studies for epistasis detection have been conducted, so far few studies can demonstrate replicable epistasis. In the present work, we propose a minimal protocol for exhaustive genome-wide association interaction (GWAI) analysis that involves screening for epistasis over large-scale genomic data combining strengths of different methods and statistical tools. The different steps of this protocol are illustrated on a real-life data application for Alzheimer’s disease (a large cohort of 2259 patients and 6017 controls from France). Using this protocol, we identified AD-associated interacting SNPs-pair from chromosome 6q11.1 (rs6455128, the KHDRBS2 gene) and 13q12.11 (rs7989332, the CRYL1 gene) and male-specific epistasis between SNPs from chromosome 5q34 (rs729149 and rs3733980, the WWC1 gene) and 15q22.2 (rs9806612, rs9302230 and rs7175766, the TLN2 gene). The transcriptome analysis revealed negative correlation between expression levels of KHDRBS2 and CRYL1 in both the temporal cortex and cerebellum brain regions and positive correlation between the expression levels of CRYL1 and WWC1 in the temporal cortex brain region. A replication analysis strategy and a meta-analysis approach in independent data confirmed effects of some of the discovered interactions. [less ▲]

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See detailGenome-wide association interaction analysis for complex diseases: an example on Alzheimer’s disease.
Gusareva, Elena ULg; Cuyvers, E; Colon, S et al

Poster (2013, April)

Objectives: Common genetic mutations that can be detected via a genome-wide association (GWA) study and at the same time have a strong contribution to disease risk are fairly limited. Some of the genetic ... [more ▼]

Objectives: Common genetic mutations that can be detected via a genome-wide association (GWA) study and at the same time have a strong contribution to disease risk are fairly limited. Some of the genetic variants in humans are either rare, thus more difficult to be identified, or they are common, but exert relatively small or even no individual effects that are masked or enhanced by one or several genes. The discovery of interacting genetic variants, possibly explaining part of the hidden genetic heritability, requires the development of sophisticated strategies and bioinformatics tools. Methods: In the present study, we propose a minimal protocol for genome-wide association interaction (GWAI) analysis that involves screening over large-scale genomic data in the search for epistatic or synergetic effects. The different steps of this minimal protocol are illustrated on a real-life data application for Alzheimer disease (AlzD) (large human cohort of 2,259 cases and 6,017 controls from France) and the pros and cons of the approaches are discussed. Results: Using the protocol, we identified two pairs of AlzD-associated interacting SNPs: from chromosome 6q11.1 and 13q12.11 and male-specific epistasis between SNPs from chromosome 5q34 and 15q22.2. Conclusion: In the present work we developed and applied an epistasis detection protocol to perform a comprehensive genome-wide search for AlzD-associated epistatic effects, hereby combining the strengths of different strategies, methods and statistical tools. It is the first time an epistasis study of this magnitude has been conducted in the context of AlzD. We show the advantages of viewing and analyzing data from different angles. A replication analysis strategy adapted to the epistasis detection context, as well as a meta-analytic approach confirmed effects of the discovered interactions. Apart from the biological and clinical importance, the present work offers a roadmap for future investigations in the field of epistasis detection and interpretation. [less ▲]

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See detailGenome-wide association study for milk fatty acid composition using cow versus bull data
Bastin, Catherine ULg; Gengler, Nicolas ULg; Soyeurt, Hélène ULg et al

in Book of Astracts of the 63rd Annual Meeting of the European Federation of Animal Science (2012)

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See detailGenome-wide association study identifies sequence variants within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm.
Gretarsdottir, Solveig; Baas, Annette F.; Thorleifsson, G. et al

in Nature Genetics (2010)

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See detailGenome-wide association study of migraine implicates a common susceptibility variant on 8q22.1.
Anttila, Verneri; Stefansson, Hreinn; Kallela, Mikko et al

in Nature Genetics (2010), 42(10), 869-73

Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular ... [more ▼]

Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 x 10, odds ratio = 1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis P value of 1.69 x 10(1)(1) (odds ratio = 1.18, 95% CI 1.127-1.244). rs1835740 is located between MTDH (astrocyte elevated gene 1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In an expression quantitative trait study in lymphoblastoid cell lines, transcript levels of the MTDH were found to have a significant correlation to rs1835740 (P = 3.96 x 10, permuted threshold for genome-wide significance 7.7 x 10. To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine. [less ▲]

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See detailGenome-wide Determinants of Proviral Targeting, Clonal Abundance and Expression in Natural HTLV-1 Infection.
Melamed, Anat; Laydon, Daniel J.; Gillet, Nicolas ULg et al

in PLoS Pathogens (2013), 9(3), 1003271

The regulation of proviral latency is a central problem in retrovirology. We postulate that the genomic integration site of human T lymphotropic virus type 1 (HTLV-1) determines the pattern of expression ... [more ▼]

The regulation of proviral latency is a central problem in retrovirology. We postulate that the genomic integration site of human T lymphotropic virus type 1 (HTLV-1) determines the pattern of expression of the provirus, which in turn determines the abundance and pathogenic potential of infected T cell clones in vivo. We recently developed a high-throughput method for the genome-wide amplification, identification and quantification of proviral integration sites. Here, we used this protocol to test two hypotheses. First, that binding sites for transcription factors and chromatin remodelling factors in the genome flanking the proviral integration site of HTLV-1 are associated with integration targeting, spontaneous proviral expression, and in vivo clonal abundance. Second, that the transcriptional orientation of the HTLV-1 provirus relative to that of the nearest host gene determines spontaneous proviral expression and in vivo clonal abundance. Integration targeting was strongly associated with the presence of a binding site for specific host transcription factors, especially STAT1 and p53. The presence of the chromatin remodelling factors BRG1 and INI1 and certain host transcription factors either upstream or downstream of the provirus was associated respectively with silencing or spontaneous expression of the provirus. Cells expressing HTLV-1 Tax protein were significantly more frequent in clones of low abundance in vivo. We conclude that transcriptional interference and chromatin remodelling are critical determinants of proviral latency in natural HTLV-1 infection. [less ▲]

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See detailGenome-wide environmental interaction analysis using multidimensional data reduction principles to identify asthma pharmacogenetic loci in relation to corticosteroid therapy
Van Lishout, François ULg; Bessonov, Kyrylo ULg; Duan, Quingling et al

Poster (2013, October 25)

Genome-wide gene-environment (GxE) and gene-gene (GxG) interaction studies share a lot of challenges via the common genetic component they involve. GWEI studies may therefore benefit from the abundance of ... [more ▼]

Genome-wide gene-environment (GxE) and gene-gene (GxG) interaction studies share a lot of challenges via the common genetic component they involve. GWEI studies may therefore benefit from the abundance of methodologies that are available in the context of genome-wide epistasis detection methods. One of these is Model-Based Multifactor Dimensionality Reduction (MB-MDR), which does not make any assumption about the genetic inheritance model. MB-MDR involves reducing a high-dimensional GxE space to GxE factor levels that either exhibit high or low or no evidence for their association to disease outcome. In contrast to logistic regression and random forests, MB-MDR can be used to detect GxE interactions in the absence of any main effects or when sample sizes are too small to be able to model all main and GxE interaction effects. In this ongoing study, we demonstrate the opportunities and challenges of MB-MDR for genome-wide GxE interaction analysis and analyzed the difference in prebronchodilator FEV1 following 8 weeks of inhaled corticosteroid therapy, for 565 pediatric Caucasian CAMP (ages 5-12) from the SHARE project. [less ▲]

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See detailGenome-wide Epistasis Screening for Alzheimer‘s Disease
Gusareva, Elena ULg; Bellenguez, C; Sleegers, K et al

Poster (2013, March)

Objectives: Alzheimer disease (AlzD) is a complex, progressive neurodegenerative disease where dementia symptoms (memory and other intellectual abilities loss) gradually worsen over a number of years. The ... [more ▼]

Objectives: Alzheimer disease (AlzD) is a complex, progressive neurodegenerative disease where dementia symptoms (memory and other intellectual abilities loss) gradually worsen over a number of years. The disease is characterized by the neuropathologic findings of neurofibrillary tangles and amyloid plaques that accumulate in vulnerable brain regions. AlzD is inherited as complex trait and appears to be highly heritable with 58-79 percent attributable to genetic factors. So far, although a number of main-effect genes have been identified, only a fraction of AlzD cases can be explained by specific gene mutations. In our study we performed an exhaustive and selective genome-wide screening for SNP-SNP interactions associated with AlzD in a large case/control cohort to reveal hidden heritability that can be accounted for by epistasis. Methods: We developed a minimal protocol for genome-wide association interaction (GWAI) analysis that involves screening over large-scale genomic data in the search for epistatic or synergetic effects. The protocol was applied on a large human cohort of 2,259 cases AlzD cases and 6,017 healthy controls from France to search for AlzD-associated epistasic effects. Results: In the exhaustive genome-wide screening, we identified two pairs of AlzD-associated interacting SNPs from chromosomes 6q11.1 and 13q12.11, and male-specific epistasis between SNPs from chromosomes 5q34 and 15q22.2. In the selective epistasis search, screening over the candidate genes for AlzD previously reported to be in interaction, we replicated seven out of twelve AlzD-associated gene pairs (INS / PPARA, IL1A / PPARA, IL10 / PPARA, TF / HFE, MTHFR / IL6, ABCA1 / NPC1, LRP1 / MAPT). Conclusion: It is the first time an epistasis study of this magnitude has been conducted in the context of AlzD. We show the advantages of viewing and analyzing data from different angles. A replication analysis strategy adapted to the epistasis detection context, as well as a meta-analytic approach confirmed effects of the discovered interactions. Apart from the biological and clinical importance, the present work offers a roadmap for future investigations in the field of epistasis detection and interpretation. [less ▲]

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