Search results for "Variant"

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…

Nucleotide sequence of rat invariant γ chain cDNA clone pLRγ34.3

1988

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…

PSD3 downregulation confers protection against fatty liver disease

2022

Fatty liver disease (FLD) is a growing health issue with burdening unmet clinical needs. FLD has a genetic component but, despite the common variants already identified, there is still a missing heritability component. Using a candidate gene approach, we identify a locus (rs71519934) at the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene resulting in a leucine to threonine substitution at position 186 of the protein (L186T) that reduces susceptibility to the entire spectrum of FLD in individuals at risk. PSD3 downregulation by short interfering RNA reduces intracellular lipid content in primary human hepatocytes cultured in two and three dimensions, and in human and rodent hepatoma cell…

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…

Non-equivariant cylindrical contact homology

2013

It was pointed out by Eliashberg in his ICM 2006 plenary talk that the integrable systems of rational Gromov-Witten theory very naturally appear in the rich algebraic formalism of symplectic field theory (SFT). Carefully generalizing the definition of gravitational descendants from Gromov-Witten theory to SFT, one can assign to every contact manifold a Hamiltonian system with symmetries on SFT homology and the question of its integrability arises. While we have shown how the well-known string, dilaton and divisor equations translate from Gromov-Witten theory to SFT, the next step is to show how genus-zero topological recursion translates to SFT. Compatible with the example of SFT of closed …

Relation Between Genetic Factors and Frailty in Older Adults.

2018

Frailty is a geriatric syndrome that identifies individuals at higher risk of disability, institutionalization, and death. We previously reported that frailty is related to oxidative stress and cognitive impairment-related biomarkers. The aim of this study was to determine whether frailty is associated with genetic variants.Longitudinal population-based cohort of 2488 community-dwelling people from Toledo, Spain, aged 65 years or older.We obtained blood samples from 78 individuals with frailty and 74 nonfrail individuals who were nonfrail (according to Fried criteria) from the Toledo Study of Healthy Ageing and extracted DNA using the Chemagic DNA blood kit.Sample genotyping was carried out…