Search results for " Heterozygosity"
showing 10 items of 141 documents
Identification of a novel compound heterozygote SCO2 mutation in cytochrome c oxidase deficient fatal infantile cardioencephalomyopathy
2006
UNLABELLED Fatal infantile cardioencephalomyopathy (OMIM No. 604377) is a disorder of the mitochondrial respiratory chain and is characterised by neonatal progressive muscular hypotonia and cardiomyopathy because of severe Cytochrome c oxidase deficiency. Here we report a novel mutation in the Cytochrome c oxidase assembly gene SCO2 in an infant with fatal infantile cardioencephalomyopathy despite normal initial metabolic screening. CONCLUSION In newborns with unexplained muscular hypotonia and cardiomyopathy genetic testing of mitochondrial respiratory chain disorders might be helpful to establish a final diagnosis and guide treatment decisions.
CFTR p.Arg117His associated with CBAVD and other CFTR-related disorders
2013
International audience; BACKGROUND:The high frequency of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene mutation p.Arg117His in patients with congenital bilateral absence of the vas deferens (CBAVD) and in newborns screened for CF has created a dilemma.METHODS:Phenotypic and genotypic data were retrospectively collected in 179 non-newborn French individuals carrying p.Arg117His and a second CFTR mutation referred for symptoms or family history, by all French molecular genetics laboratories, referring physicians, CF care centres and infertility clinics.RESULTS:97% of the patients had the intronic T7 normal variant in cis with p.Arg117His. 89% patients were male, wit…
A region on human chromosome 4 (q35.1→qter) induces senescence in cell hybrids and is involved in cervical carcinogenesis
2005
Human papillomavirus (HPV) types 16 and 18 are known to play a major role in cervical carcinogenesis. Additional genetic alterations are required for the development and progression of cervical cancer. Previously, we showed that the introduction of an entire human chromosome 4 into HPV-immortalized cells by microcell-mediated chromosome transfer (MMCT) can induce senescence in cell hybrids. In the present study, we established eight new murine donor cell lines harboring different fragments of the human chromosome 4. These were tested for their ability to induce senescence by MMCT into HPV16-immortalized keratinocytes (HPK II) and cervical carcinoma cells (HeLa). By exclusion, we could ident…
The influence of land use on the genetic structure of populations of the common frog Rana temporaria
1990
In order to find out the influence of land use and topographic distance on the genetic structure of populations of the common frog Rana temporaria L. in the Saar-Palatinate lowlands (Federal Republic of Germany), tissue of larvae was examined by means of horizontal starch gel electrophoresis. A total of 24 loci coding for 14 different enzymes were studied. Genotype frequencies, allele frequencies and mean heterozygosity were calculated, and genetic distances using Nei's formula. Strong deviations from the Hardy-Weinberg equilibrium were found; the degree of homozygosity was higher than expected. Separation by highways reduced average heterozygosity as well as genetic polymorphism of local p…
Sex-specific impact of inbreeding on pathogen load in the striped dolphin.
2020
The impact of inbreeding on fitness has been widely studied and provides consequential inference about adaptive potential and the impact on survival for reduced and fragmented natural populations. Correlations between heterozygosity and fitness are common in the literature, but they rarely inform about the likely mechanisms. Here, we investigate a pathology with a clear impact on health in striped dolphin hosts (a nematode infection that compromises lung function). Dolphins varied with respect to their parasite burden of this highly pathogenic lung nematode (Skrjabinalius guevarai). Genetic diversity revealed by high-resolution restriction-associated DNA (43 018 RADseq single nucleotide pol…
Genetic dissimilarity between mates, but not male heterozygosity, influences divorce in schistosomes.
2008
6 pages; International audience; Background: Correlational studies strongly suggest that both genetic similarity and heterozygosity can influence female mate choice. However, the influence of each variable has usually been tested independently, although similarity and heterozygosity might be correlated. We experimentally determined the relative influence of genetic similarity and heterozygosity in divorce and re-mating in the monogamous endoparasite Schistosoma mansoni. Methodology/Principal Findings: We performed sequential infections of vertebrate hosts with controlled larval populations of parasites, where sex and individual genetic diversity and similarity were predetermined before infe…
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…
SPRED1, a RAS MAPK pathway inhibitor that causes Legius syndrome, is a tumour suppressor downregulated in paediatric acute myeloblastic leukaemia
2013
Constitutional dominant loss-of-function mutations in the SPRED1 gene cause a rare phenotype referred as neurofibromatosis type 1 (NF1)-like syndrome or Legius syndrome, consisted of multiple café-au-lait macules, axillary freckling, learning disabilities and macrocephaly. SPRED1 is a negative regulator of the RAS MAPK pathway and can interact with neurofibromin, the NF1 gene product. Individuals with NF1 have a higher risk of haematological malignancies. SPRED1 is highly expressed in haematopoietic cells and negatively regulates haematopoiesis. SPRED1 seemed to be a good candidate for leukaemia predisposition or transformation. We performed SPRED1 mutation screening and expression status i…
Telomerase reverse transcriptase germline mutations and hepatocellular carcinoma in patients with nonalcoholic fatty liver disease
2017
Abstract In an increasing proportion of cases, hepatocellular carcinoma (HCC) develops in patients with nonalcoholic fatty liver disease (NAFLD). Mutations in telomerase reverse transcriptase (hTERT) are associated with familial liver diseases. The aim of this study was to examine telomere length and germline hTERT mutations as associated with NAFLD‐HCC. In 40 patients with NAFLD‐HCC, 45 with NAFLD‐cirrhosis and 64 healthy controls, peripheral blood telomere length was evaluated by qRT‐PCR and hTERT coding regions and intron–exon boundaries sequenced. We further analyzed 78 patients affected by primary liver cancer (NAFLD‐PLC, 76 with HCC). Enrichment of rare coding mutations (allelic frequ…
Neuroblastoma after Childhood: Prognostic Relevance of Segmental Chromosome Aberrations, ATRX Protein Status, and Immune Cell Infiltration
2014
AbstractNeuroblastoma (NB) is a common malignancy in children but rarely occurs during adolescence or adulthood. This subgroup is characterized by an indolent disease course, almost uniformly fatal, yet little is known about the biologic characteristics. The aim of this study was to identify differential features regarding DNA copy number alterations, α-thalassemia/mental retardation syndrome X-linked (ATRX) protein expression, and the presence of tumor-associated inflammatory cells. Thirty-one NB patients older than 10 years who were included in the Spanish NB Registry were considered for the current study; seven young and middle-aged adult patients (range 18-60 years) formed part of the c…