Search results for "LOCUS"
showing 10 items of 632 documents
Resolving the locus of cAsE aLtErNaTiOn effects in visual word recognition: Evidence from masked priming.
2015
Determining the factors that modulate the early access of abstract lexical representations is imperative for the formulation of a comprehensive neural account of visual-word identification. There is a current debate on whether the effects of case alternation (e.g., tRaIn vs. train) have an early or late locus in the word-processing stream. Here we report a lexical decision experiment using a technique that taps the early stages of visual-word recognition (i.e., masked priming). In the design, uppercase targets could be preceded by an identity/unrelated prime that could be in lowercase or alternating case (e.g., table-TABLE vs. crash-TABLE; tAbLe-TABLE vs. cRaSh-TABLE). Results revealed that…
Genetic signature consistent with selection against the CYP3A4*1B allele in non-African populations.
2005
Cytochrome P450 3A enzymes (CYP3A) play a major role in the metabolism of steroid hormones, drugs and other chemicals, including many carcinogens. The individually variable CYP3A expression, which remains mostly unexplained, has been suggested to affect clinical phenotypes. We investigated the CYP3A locus in five ethnic groups. The degree of linkage disequilibrium (LD) differed among ethnic groups, but the most common alleles of the conserved LD regions were remarkably similar. Non-African haplotypes are few; for example, only four haplotypes account for 80% of common European Caucasian alleles. Large LD blocks of high frequencies were suggestive of selection. Accordingly, European Caucasia…
Genome wide identification of new genes and pathways in patients with both autoimmune thyroiditis and type 1 diabetes
2015
Autoimmune thyroid diseases (AITD) and Type 1 diabetes (T1D) frequently occur in the same individual pointing to a strong shared genetic susceptibility. Indeed, the co-occurrence of T1D and AITD in the same individual is classified as a variant of the autoimmune polyglandular syndrome type 3 (designated APS3v). Our aim was to identify new genes and mechanisms causing the co-occurrence of T1D + AITD (APS3v) in the same individual using a genome-wide approach. For our discovery set we analyzed 346 Caucasian APS3v patients and 727 gender and ethnicity matched healthy controls. Genotyping was performed using the Illumina Human660W-Quad.v1. The replication set included 185 APS3v patients and 340…
Polymorphisms in FTO and near TMEM18 associate with type 2 diabetes and predispose to younger age at diagnosis of diabetes
2013
Variations in the FTO gene and near the TMEM18 gene are risk factors for common form of obesity, but have also been linked with type 2 diabetes (T2D). Our aim was to investigate the contribution of these variants to risk of T2D in a population in Latvia. Four single nucleotide polymorphisms (SNP) in the first and fourth intronic regions of FTO and one close to TMEM18 were genotyped in 987 patients with T2D and 1080 controls selected from the Latvian Genome Data Base (LGDB). We confirmed association of SNPs in the first intron (rs11642015, rs62048402 and rs9939609) of FTO and rs7561317 representing the TMEM18 locus with T2D. Association between SNP in FTO and T2D remained significant after c…
GENETIC BASIS OF THE TRADE-OFF BETWEEN OFFSPRING NUMBER AND QUALITY IN THE BANK VOLE
2004
One of the main tenets of modern life-history theory is the negative relationship (trade-off) between the number and quality of offspring produced. Theory predicts a negative genetic correlation between these traits since both are closely related to fitness of individuals. However, the genetic basis of the trade-off has only been tested to a limited extent in natural populations. We examined whether size and quality of offspring are negatively related to litter size in the bank vole Clethrionomys glareolus. First, we found a significant negative phenotypic correlation between the number and size of offspring at birth in both laboratory and field populations of the bank vole. Second, a large…
An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.
2021
[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 77…
International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways
2015
Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist.
Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis.
2010
A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10−11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10−10, OR = 1.63) and 17q12-21 (P = 1.7 × 10−10, OR = 1.38).
Incomplete sequence homogenization in 45S rDNA multigene families: intermixed IGS heterogeneity within the single NOR locus of the polyploid species …
2014
† Background and Aims Ribosomal sequences have become the classical example of the genomic homogenization of nuclear multigene families. Despite theoretical advantages and modelling predictions that support concerted evolution of the 45S rDNA, several reports have found intragenomic polymorphisms. However, the origins and causes of these rDNA polymorphisms are difficult to assess because seed plants show a wide range of 45S rDNA loci number variation, especially in polyploids. Medicago arborea is a tetraploid species that has a single 45S rDNA locus. This feature makes this species a suitable case study to assess the fate of ribosomal IGS homogenization in polyploid species showing nucleolu…
Reliability and Intersession Agreement of Microperimetric and Fixation Measurements Obtained with a New Microperimeter in Normal Eyes.
2015
Purpose: To evaluate the reliability and intersession agreement of measurements of retinal sensitivity as well as of the fixation pattern obtained in healthy eyes with a microperimeter integrating the mechanism of the scanning laser ophthalmoscope (SLO) with the static perimetry. Methods: This study included a sample of 44 healthy eyes of 44 subjects of a mean age of 27.0 ± 8.5 years. In all cases, microperimetric exams with the MAIA system (Centervue, Padova, Italy) were performed in three different sessions to evaluate the intersession repeatability. The consistency of measurements was analyzed by using the Friedman test and by analyzing the correlation between consecutive measurements. A…