Search results for " loci"
showing 10 items of 227 documents
Localization of quantitative trait loci for diapause and other photoperiodically regulated life history traits important in adaptation to seasonally …
2015
Seasonally changing environments at high latitudes present great challenges for the reproduction and survival of insects, and photoperiodic cues play an important role in helping them to synchronize their life cycle with prevalent and forthcoming conditions. We have mapped quantitative trait loci (QTL) responsible for the photoperiodic regulation of four life history traits, female reproductive diapause, cold tolerance, egg-to-eclosion development time and juvenile body weight in Drosophila montana strains from different latitudes in Canada and Finland. The F2 progeny of the cross was reared under a single photoperiod (LD cycle 16:8), which the flies from the Canadian population interpret a…
X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis
2021
Background & aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds…
MLL-Rearranged Leukemia Is Dependent on Aberrant H3K79 Methylation by DOT1L
2011
SummaryThe histone 3 lysine 79 (H3K79) methyltransferase Dot1l has been implicated in the development of leukemias bearing translocations of the Mixed Lineage Leukemia (MLL) gene. We identified the MLL-fusion targets in an MLL-AF9 leukemia model, and conducted epigenetic profiling for H3K79me2, H3K4me3, H3K27me3, and H3K36me3 in hematopoietic progenitor and leukemia stem cells (LSCs). We found abnormal profiles only for H3K79me2 on MLL-AF9 fusion target loci in LSCs. Inactivation of Dot1l led to downregulation of direct MLL-AF9 targets and an MLL translocation-associated gene expression signature, whereas global gene expression remained largely unaffected. Suppression of MLL translocation-a…
Genome-Wide Haplotype Analysis of Cis Expression Quantitative Trait Loci in Monocytes
2013
In order to assess whether gene expression variability could be influenced by several SNPs acting in cis, either through additive or more complex haplotype effects, a systematic genome-wide search for cis haplotype expression quantitative trait loci (eQTL) was conducted in a sample of 758 individuals, part of the Cardiogenics Transcriptomic Study, for which genome-wide monocyte expression and GWAS data were available. 19,805 RNA probes were assessed for cis haplotypic regulation through investigation of ∼2,1×109 haplotypic combinations. 2,650 probes demonstrated haplotypic p-values >104-fold smaller than the best single SNP p-value. Replication of significant haplotype effects were tested f…
Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort
2013
The work conducted at the WTCHG was supported by Wellcome Trust grants [076566/Z/05/Z] and [075491/Z/04]; the work in Zurich partly by an SNSF grant [32-108130]. We also thank MAF (Mutation Analysis core Facility) at the Karolinska Institute, Novum, Huddinge. The French part of the project was funded by Agence Nationale de la Recherche (ANR-06-NEURO-019-01 GENEDYS) and Ville de Paris. S Paracchini is a Royal Society University Research Fellow. D Czamara was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) within the framework of the Munich Cluster for Systems Neurology (EXC 1010 SyNergy). Dyslexia is one of the most common childhood disorders with a prevalence o…
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
2010
We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 x 10(-8)). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with gen…
Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
2013
Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional…
Long-range DNA looping and gene expression analyses identify DEXI as an autoimmune disease candidate gene
2011
The chromosome 16p13 region has been associated with several autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). CLEC16A has been reported as the most likely candidate gene in the region, since it contains the most disease-associated single-nucleotide polymorphisms (SNPs), as well as an imunoreceptor tyrosine-based activation motif. However, here we report that intron 19 of CLEC16A, containing the most autoimmune disease-associated SNPs, appears to behave as a regulatory sequence, affecting the expression of a neighbouring gene, DEXI. The CLEC16A alleles that are protective from T1D and MS are associated with increased expression of DEXI, and no other genes in …
Heterozygote Advantage Probably Maintains Rhesus Factor Blood Group Polymorphism: Ecological Regression Study
2016
Rhesus factor polymorphism has been an evolutionary enigma since its discovery in 1939. Carriers of the rarer allele should be eliminated by selection against Rhesus positive children born to Rhesus negative mothers. Here I used an ecologic regression study to test the hypothesis that Rhesus factor polymorphism is stabilized by heterozygote advantage. The study was performed in 65 countries for which the frequencies of RhD phenotypes and specific disease burden data were available. I performed multiple multivariate covariance analysis with five potential confounding variables: GDP, latitude (distance from the equator), humidity, medical care expenditure per capita and frequencies of smokers…
Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci
2011
Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4-7.5% of individuals with inflammatory bowel disease. We performed a genome-wide association analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 x 10(-16) and P = 4.1 x 10(-8), respectively).