Search results for "MOZ"
showing 10 items of 437 documents
Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation
2019
Background & Aims Alpha-1 antitrypsin deficiency (AATD) is among the most common genetic disorders. Severe AATD is caused by a homozygous mutation in the SERPINA1 gene that encodes the Glu342Lys substitution (called the Pi*Z mutation, Pi*ZZ genotype). Pi*ZZ carriers may develop lung and liver diseases. Mutation-associated lung disorders have been well studied, but less is known about the effects in liver. We assessed the liver disease burden and associated features in adults with this form of AATD. Methods We collected data from 554 Pi*ZZ adults (403 in an exploratory cohort, 151 in a confirmatory cohort), in 9 European countries, with AATD who were homozygous for the Pi*Z mutation, and 234…
Management of chronic viral hepatitis in patients with thalassemia: recommendations from an international panel.
2010
AbstractChelation therapy with new drugs prevents cardiac damage and improves the survival of thalassemia patients. Liver diseases have emerged as a critical clinical issue. Chronic liver diseases play an important role in the prognosis of thalassemia patients because of the high frequency of viral infections and important role of the liver in regulating iron metabolism. Accurate assessment of liver iron overload is required to tailor iron chelation therapy. The diagnosis of hepatitis B virus– or hepatitis C virus–related chronic hepatitis is required to detect patients who have a high risk of developing liver complications and who may benefit by antiviral therapy. Moreover, clinical manage…
Symplekin, a polyadenylation factor, prevents MOZ and MLL activity on HOXA9 in hematopoietic cells
2013
International audience; MOZ and MLL encoding a histone acetyltransferase and a histone methyltransferase, respectively, are targets for recurrent chromosomal translocations found in acute myeloblastic or lymphoblastic leukemia. We have previously shown that MOZ and MLL cooperate to activate HOXA9 gene expression in hematopoietic stem/progenitors cells. To dissect the mechanism of action of this complex, we decided to identify new proteins interacting with MOZ. We found that the scaffold protein Symplekin that supports the assembly of polyadenylation machinery was identified by mass spectrometry. Symplekin interacts and co-localizes with both MOZ and MLL in immature hematopoietic cells. Its …
Successive Invasion-Mediated Interspecific Hybridizations and Population Structure in the Endangered Cichlid Oreochromis mossambicus.
2013
Hybridization between invasive and native species accounts among the major and pernicious threats to biodiversity. The Mozambique tilapia Oreochromis mossambicus, a widely used freshwater aquaculture species, is especially imperiled by this phenomenon since it is recognized by the IUCN as an endangered taxon due to genetic admixture with O. niloticus an invasive congeneric species. The Lower Limpopo and the intermittent Changane River (Mozambique) drain large wetlands of potentially great importance for conservation of O. mossambicus, but their populations have remained unstudied until today. Therefore we aimed (1) to estimate the autochthonous diversity and population structure among genet…
Deletion of 11q in Neuroblastomas Drives Sensitivity to PARP Inhibition
2017
AbstractPurpose: Despite advances in multimodal therapy, neuroblastomas with hemizygous deletion in chromosome 11q (20%–30%) undergo consecutive recurrences with poor outcome. We hypothesized that patients with 11q-loss may share a druggable molecular target(s) that can be exploited for a precision medicine strategy to improve treatment outcome.Experimental Design: SNP arrays were combined with next-generation sequencing (NGS) to precisely define the deleted region in 17 primary 11q-loss neuroblastomas and identify allelic variants in genes relevant for neuroblastoma etiology. We assessed PARP inhibitor olaparib in combination with other chemotherapy medications using both in vitro and in v…
Genome-wide identification of runs of homozygosity islands and associated genes in local dairy cattle breeds
2018
Runs of homozygosity (ROH) are widely used as predictors of whole-genome inbreeding levels in cattle. They identify regions that have an unfavorable effect on a phenotype when homozygous, but also identify the genes associated with traits of economic interest present in these regions. Here, the distribution of ROH islands and enriched genes within these regions in four dairy cattle breeds were investigated. Cinisara (71), Modicana (72), Reggiana (168) and Italian Holstein (96) individuals were genotyped using the 50K v2 Illumina BeadChip. The genomic regions most commonly associated with ROHs were identified by selecting the top 1% of the single nucleotide polymorphisms (SNPs) most commonly…
Genome-wide analysis in endangered populations: a case study in Barbaresca sheep
2017
Analysis of genomic data is becoming increasingly common in the livestock industry and the findings have been an invaluable resource for effective management of breeding programs in small and endangered populations. In this paper, with the goal of highlighting the potential of genomic analysis for small and endangered populations, genome-wide levels of linkage disequilibrium, measured as the squared correlation coefficient of allele frequencies at a pair of loci, effective population size, runs of homozygosity (ROH) and genetic diversity parameters, were estimated in Barbaresca sheep using Illumina OvineSNP50K array data. Moreover, the breed's genetic structure and its relationship with oth…
The At Risk Child Clinic (ARCC): 3 Years of Health Activities in Support of the Most Vulnerable Children in Beira, Mozambique
2018
The concept of “children at risk” changes worldwide according to each specific context. Africa has a large burden of overall risk factors related to childhood health and development, most of which are of an infective or social origin. The aim of this study was to report and analyze the volumes of activities of fifteen At Risk Child Clinics (ARCCs) within the Beira District (Mozambique) over a 3 year-period in order to define the health profile of children accessing such health services. We retrospectively analyzed the data from all of the children accessing one of the 15 Beira ARCCs from January 2015 to December 2017. From this, 17,657 first consultations were registered. The mo…
Homozygous Familial Hypercholesterolemia in Spain Prevalence and Phenotype-Genotype Relationship
2016
Background— Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor ( LDLR ), apolipoprotein B ( APOB ), proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), and LDL protein receptor adaptor 1 ( LDLRAP1 ). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition. Here, we aimed to characterize HoFH in Spain. Methods and Results— Data were collected from the Spanish Dyslipidemia Regist…
Generation of an iPSC line (UNINAi001-A) from a girl with neonatal-onset epilepsy and non-syndromic intellectual disability carrying the homozygous K…
2021
Abstract Heterozygous variants in the KCNQ3 gene cause epileptic and/or developmental disorders of varying severity. Here we describe the generation of induced pluripotent stem cells (iPSCs) from a 9-year-old girl with pharmacodependent neonatal-onset epilepsy and intellectual disability who carry a homozygous single-base duplication in exon 12 of KCNQ3 (NM_004519.3: KCNQ3 c.1599dup; KCNQ3 p.PHE534ILEfs*15), and from a non-carrier brother of the proband. For iPSC generation, non-integrating episomal plasmid vectors were used to transfect fibroblasts isolated from skin biopsies. The obtained iPSC lines had a normal karyotype, showed embryonic stem cell-like morphology, expressed pluripotency…