Search results for "Intron"

A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol

2012

Serum lipid levels have been associated with cardiovascular diseases, metabolic syndrome and type II diabetes (Kannel et al., 1961; Miller & Miller, 1975; Pilia et al., 2006). Variation in lipids levels is highly influenced by heritable factors (Friedlander et al., 1997) and 95 loci have already been associated with levels of high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides (TG) and total cholesterol (TC) in numerous study samples and replicated in various populations using genome-wide approaches (Aulchenko et al., 2008; Kathiresan et al., 2008; Kooner et al., 2008; Teslovich et al., 2010; Willer et al., 2008). However, the genetic associa…

Six novel mutations of the LDL receptor gene in FH kindred of Sicilian and Paraguayan descent

2006

Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease caused by mutations in the gene coding for the low density lipoprotein receptor (LDL-R). It is characterized by a high concentration of low density lipoprotein (LDL), which frequently gives rise to premature coronary artery disease. We studied the probands of five FH Sicilian families with 'definite' FH and one proband of Paraguayan descent with homozygous FH who has been treated with an effective living-donor liver transplantation. In order to seek the molecular defect in these six families, we used direct sequencing to define the molecular defects of the LDL-R gene responsible for the disease. We described three…

The Peroxisomal 3-keto-acyl-CoA thiolase B Gene Expression Is under the Dual Control of PPARα and HNF4α in the Liver

2011

PPARα and HNF4α are nuclear receptors that control gene transcription by direct binding to specific nucleotide sequences. Using transgenic mice deficient for either PPARα or HNF4α, we show that the expression of the peroxisomal3-keto-acyl-CoA thiolase B(Thb) is under the dependence of these two transcription factors. Transactivation and gel shift experiments identified a novel PPAR response element within intron 3 of theThbgene, by which PPARα but not HNF4α transactivates. Intriguingly, we found that HNF4α enhanced PPARα/RXRα transactivation from TB PPRE3 in a DNA-binding independent manner. Coimmunoprecipitation assays supported the hypothesis that HNF4α was physically interacting with RXR…

A molecular phylogeny of bullfinches Pyrrhula Brisson, 1760 (Aves: Fringillidae)

2011

Abstract We present a molecular phylogeny of bullfinches (Pyrrhula Brisson, 1760) based on 2357 bp DNA sequence information of mitochondrial genes (cyt-b, 16S rRNA) and nuclear introns (fib-7, GAPDH-11). The genus is clearly a monophyletic group. Within the limits of Pyrrhula, molecular methods support the subdivision of three main groups: (1) “Southeast-Asian bullfinches” (P. nipalensis and P. leucogenis), (2) “Himalayan bullfinches” (P. aurantiaca, P. erythaca, P. erythrocephala), and (3) “Eurasian bullfinches” (P. pyrrhula s.l.). Within the last group there are four different subgroups: (3a) P. (p.) murina, (3b) P. (p.) cineracea, (3c) P. (p.) griseiventris, and (3d) P. pyrrhula s.str. T…

2015

The combination of Reverse Transcription (RT) and high-throughput sequencing has emerged as a powerful combination to detect modified nucleotides in RNA via analysis of either abortive RT-products or of the incorporation of mismatched dNTPs into cDNA. Here we simultaneously analyze both parameters in detail with respect to the occurrence of N-1-methyladenosine (m(1)A) in the template RNA. This naturally occurring modification is associated with structural effects, but it is also known as a mediator of antibiotic resistance in ribosomal RNA. In structural probing experiments with dimethylsulfate, m(1)A is routinely detected by RT-arrest. A specifically developed RNA-Seq protocol was tailored…

Intronic Variant in CNTNAP2 Gene in a Boy With Remarkable Conduct Disorder, Minor Facial Features, Mild Intellectual Disability, and Seizures

2020

Introduction: Mutations in the contactin-associated protein-like 2 (CNTNAP2) gene (MIM#604569) encoding for CASPR2, a cell adhesion protein of the neurexin family, are known to be associated with autism, intellectual disability, and other neuropsychiatric disorders. A set of intronic deletions of CNTNAP2 gene has also been suggested to have a causative role in individuals with a wide phenotypic spectrum, including Pitt-Hopkins syndrome, cortical dysplasia–focal epilepsy syndrome, Tourette syndrome, language dysfunction, and abnormal behavioral manifestations. Case presentation: A 10-years-old boy was referred to the hospital with mild intellectual disability and language impairment. Moreove…

Regulation of human inducible nitric oxide synthase expression by an upstream open reading frame.

2019

Abstract The human inducible nitric oxide synthase (iNOS) gene contains an upstream open reading frame (uORF) in its 5′-untranslated region (5′-UTR) implying a translational regulation of iNOS expression. Transfection experiments in human DLD-1 cells revealed that the uORF although translatable seems not to inhibit the translation start at the bona fide ATG. Our data clearly show that human iNOS translation is cap-dependent and that the 5′-UTR of the iNOS mRNA contains no internal ribosome entry site. Translation of the bona fide coding sequence is most likely mediated by a leaky scanning mechanism. The 5′-UTR is encoded by exon 1 and exon 2 of the iNOS gene with the uORF stop codon located…

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 …

Silicateins, the major biosilica forming enzymes present in demosponges: protein analysis and phylogenetic relationship.

2007

Silicateins are enzymes, which are restricted to sponges (phylum Porifera), that mediate the catalytic formation of biosilica from monomeric silicon compounds. The silicatein protein is compartmented in the sponges in the axial filaments which reside in the axial canals of the siliceous spicules. In the present study silicatein has been isolated from the freshwater sponge Lubomirskia baicalensis where it occurs in isoforms with sizes of 23 kDa, 24 kDa and 26 kDa. Since the larger protein is glycosylated we posit that it is a processed form of one of the smaller size forms. The silicatein isoforms are post-translationally modified by phosphorylation; at least four isoforms exist with pI's of…

Cloning of a rat-specific long PCP4/PEP19 isoform

2007

We report the identification of a cDNA that encodes a putative protein of 94 amino acids and expected molecular weight of 10.7 kDa, the C-terminal half of which is identical to that of PEP19, a small, brain-specific protein involved in Ca++/calmodulin signaling. The novel rat-specific protein, tentatively named long PEP19 isoform (LPI), is the product of alternative splicing of the rat PCP4 gene encoding PEP19. We found that antibodies raised against the first 13 N-terminal amino acids of LPI, not present in PEP19, recognize a protein enriched in the developing rat brain.