Search results for "Variants"
showing 10 items of 227 documents
Copy number variations in the etiology of epilepsy
2013
Epilepsy is one of the most common neurological disorders in humans with a prevalence of 1% and a lifetime incidence of 3%. Idiopathic epilepsies occur in the absence of identifiable causal factors, but recent evidences show the role of genetic factors in the developing of these disorders. In particular, several studies focused their attention on the role of copy number variations (CNVs) in the etiology of epilepsy. In recent years, many CNVs have been identified, like 15q11.2, 15q13.3 and 16p13.11 microdeletions, 22q11.2 microduplication and many others. Possible candidate genes included in these regions were also studied and they seem to be involved in neuronal transmission and ion transp…
Exome sequencing of three cases of familial exceptional longevity
2014
Exceptional longevity (EL) is a rare phenotype that can cluster in families, and co-segregation of genetic variation in these families may point to candidate genes that could contribute to extended lifespan. In this study, for the first time, we have sequenced a total of seven exomes from exceptionally long-lived siblings (probands ≥ 103 years and at least one sibling ≥ 97 years) that come from three separate families. We have focused on rare functional variants (RFVs) which have ≤ 1% minor allele frequency according to databases and that are likely to alter gene product function. Based on this, we have identified one candidate longevity gene carrying RFVs in all three families, APOB. Inter…
RNA-binding activity of the rat calmodulin-binding PEP-19 protein and of the long PEP-19 isoform
2012
Synthesis of H1˚ histone protein, in the developing rat brain, seems to be regulated mainly at the post-transcriptional level. Since regulation of RNA metabolism depends on a series of RNA-binding proteins, we have been searching for RNA-binding proteins involved in the post-transcriptional regulation of the H1˚ gene. We recently reported isolation, from a cDNA expression library, of an insert encoding a novel protein, the C-terminal half of which is identical to that of PEP-19, a brain-specific protein involved in calcium metabolism. The novel protein was called long PEP-19 isoform (LPI). Herein we show that LPI, as well as PEP-19, can bind H1˚ RNA. Moreover, in order to improve production…
Functional annotation of genes overlapping copy number variants in autistic patients: focus on axon pathfinding.
2010
We have used Gene Ontology (GO) and pathway analyses to uncover the common functions associated to the genes overlapping Copy Number Variants (CNVs) in autistic patients. Our source of data were four published studies [1- 4]. We first applied a two-step enrichment strategy for autism-specific genes. We fished out from the four mentioned studies a list of 2928 genes overall overlapping 328 CNVs in patients and we first selected a sub-group of 2044 genes after excluding those ones that are also involved in CNVs reported in the Database of Genomic Variants (enrichment step 1). We then selected from the step 1-enriched list a sub-group of 514 genes each of which was found to be deleted or dupli…
DNASE1L3 Deficiency, New Phenotypes and Evidence for a Transient Type I Interferon Signaling
2021
Introduction: Deoxyribonuclease 1 like 3 (DNASE1L3) is a secreted enzyme that has been shown to digest the extracellular chromatin derived from apoptotic bodies, and DNASE1L3 pathogenic variants have been associated to a lupus phenotype. It is unclear whether interferon signaling is sustained in DNASE1L3 deficiency in humans. Objectives: Here, we report on four patients with pathogenic variations in DNASE1L3, including 2 previously undescribed causal variants, and expand the phenotype from SLE to vasculitis with gut involvement. To explore whether or not the interferon cascade was strongly and sustainably induced, Interferon stimulated genes (ISGs) expression was assessed for each patient. …
Histone-mediated transgenerational epigenetics
2019
Abstract Epigenetic mechanisms operate at the interface between the environment and genome, by converting the environmental stimuli to phenotypic responses through changes in the chromatin landscape, which ultimately affects gene expression in the absence of alterations in DNA sequence. In this scenario, transgenerational inheritance occurs when epigenetic variations induced by environmental stimuli are transmitted through the germ line to succeeding generations that had never experienced those stimuli. There is an ever-growing list of reports indicating that histones are fundamental players in these processes in a variety of organisms. In this chapter, we provide a perspective on histone-d…
The ANP Genetic Variant RS5068 is Associated With a Favorable Cardiometabolic Phenotype in a Mediterranean Population
2012
Introduction: Atrial natriuretic peptide (ANP) possesses cardiorenal protective properties including natriuresis, aldosterone suppression and vasodilation. Importantly, ANP also exerts lipolytic effects in vitro and in vivo. Previous studies reported that the ANP genetic variant rs5068 is associated with increased plasma levels of ANP, lower blood pressure values, and reduced risk of hypertension. We recently reported that in a random sample of the general population from Olmsted County, MN the G allele of rs5068 was associated with increased levels of ANP, lower blood pressure and BMI, waist circumference, reduced prevalence of obesity and metabolic syndrome. To date, these associations ha…
Genome-wide association analysis on normal hearing function identifies PCDH20 and SLC28A3 as candidates for hearing function and loss.
2015
Hearing loss and individual differences in normal hearing both have a substantial genetic basis. Although many new genes contributing to deafness have been identified, very little is known about genes/variants modulating the normal range of hearing ability. To fill this gap, we performed a two-stage meta-analysis on hearing thresholds (tested at 0.25, 0.5, 1, 2, 4, 8 kHz) and on pure-tone averages (low-, medium-and high-frequency thresholds grouped) in several isolated populations from Italy and Central Asia (total N = 2636). Here, we detected two genome-wide significant loci close to PCDH20 and SLC28A3 (top hits: rs78043697, P = 4.71E-10 and rs7032430, P = 2.39E-09, respectively). For both…
Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk.
2014
Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regressionmodels adjusting for stud…
The Links-Gould invariants as generalizations of the Alexander polynomial
2016
In this thesis we focus on the connections that exist between two link invariants: first the Alexander-Conway invariant ∆ that was the first polynomial link invariant to be discovered, and one of the most thoroughly studied since alongside with the Jones polynomial, and on the other hand the family of Links-Gould invariants LGn,m that are quantum link invariants derived from super Hopf algebras Uqgl(n|m). We prove a case of the De Wit-Ishii-Links conjecture: in some cases we can recover powers of the Alexander polynomial as evaluations of the Links-Gould invariants. So the LG polynomials are generalizations of the Alexander invariant. Moreover we give evidence that these invariants should s…