31 research outputs found

    High Frequency of Copy Number Variations and Sequence Variants at CYP21A2 Locus: Implication for the Genetic Diagnosis of 21-Hydroxylase Deficiency

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    BACKGROUND: The systematic study of the human genome indicates that the inter-individual variability is greater than expected and it is not only related to sequence polymorphisms but also to gene copy number variants (CNVs). Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (21OHD) is the most common autosomal recessive disorder with a carrier frequency of 1:25 to 1:10. The gene that encodes 21-hydroxylase enzyme, CYP21A2, is considered to be one of the most polymorphic human genes. Copy number variations, such as deletions, which are severe mutations common in 21OHD patients, or gene duplications, which have been reported as rare events, have also been described. The correct characterization of 21OHD alleles is important for disease carrier detection and genetic counselling METHODOLOGY AND FINDINGS: CYP21A2 genotyping by sequencing has been performed in a random sample of the Spanish population, where 144 individuals recruited from university students and employees of the hospital were studied. The frequency of CYP21A2 mutated alleles in our sample was 15.3% (77.3% were mild mutations, 9% were severe mutations and 13.6% were novel variants). Gene dosage assessment was also performed when CYP21A2 gene duplication was suspected. This analysis showed that 7% of individuals bore a chromosome with a duplicated CYP21A2 gene, where one of the copies was mutated. CONCLUSIONS: As far as we know, the present study has shown the highest frequency of 21OHD carriers reported by a genotyping analysis. In addition, a high frequency of alleles with CYP21A2 duplications, which could be misinterpreted as 21OHD alleles, was found. Moreover, a high frequency of novel genetic variations with an unknown effect on 21-hydroxylase activity was also found. The high frequency of gene duplications, as well as novel variations, should be considered since they have an important involvement in carrier testing and genetic counseling

    Gene Expression Profiling of Embryonic Human Neural Stem Cells and Dopaminergic Neurons from Adult Human Substantia Nigra

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    Neural stem cells (NSC) with self-renewal and multipotent properties serve as an ideal cell source for transplantation to treat neurodegenerative insults such as Parkinson's disease. We used Agilent's and Illumina Whole Human Genome Oligonucleotide Microarray to compare the genomic profiles of human embryonic NSC at a single time point in culture, and a multicellular tissue from postmortem adult substantia nigra (SN) which are rich in dopaminergic (DA) neurons. We identified 13525 up-regulated genes in both cell types of which 3737 (27.6%) genes were up-regulated in the hENSC, 4116 (30.4%) genes were up-regulated in the human substantia nigra dopaminergic cells, and 5672 (41.93%) were significantly up-regulated in both cell population. Careful analysis of the data that emerged using DAVID has permitted us to distinguish several genes and pathways that are involved in dopaminergic (DA) differentiation, and to identify the crucial signaling pathways that direct the process of differentiation. The set of genes expressed more highly at hENSC is enriched in molecules known or predicted to be involved in the M phase of the mitotic cell cycle. On the other hand, the genes enriched in SN cells include a different set of functional categories, namely synaptic transmission, central nervous system development, structural constituents of the myelin sheath, the internode region of axons, myelination, cell projection, cell somata, ion transport, and the voltage-gated ion channel complex. Our results were also compared with data from various databases, and between different types of arrays, Agilent versus Illumina. This approach has allowed us to confirm the consistency of our obtained results for a large number of genes that delineate the phenotypical differences of embryonic NSCs, and SN cells

    Discerning natural and anthropogenic organic matter inputs to salt marsh sediments of Ria Formosa lagoon (South Portugal)

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    Sedimentary organic matter (OM) origin and molecular composition provide useful information to understand carbon cycling in coastal wetlands. Core sediments from threors' Contributionse transects along Ria Formosa lagoon intertidal zone were analysed using analytical pyrolysis (Py-GC/MS) to determine composition, distribution and origin of sedimentary OM. The distribution of alkyl compounds (alkanes, alkanoic acids and alkan-2-ones), polycyclic aromatic hydrocarbons (PAHs), lignin-derived methoxyphenols, linear alkylbenzenes (LABs), steranes and hopanes indicated OM inputs to the intertidal environment from natural-autochthonous and allochthonous-as well as anthropogenic. Several n-alkane geochemical indices used to assess the distribution of main OM sources (terrestrial and marine) in the sediments indicate that algal and aquatic macrophyte derived OM inputs dominated over terrigenous plant sources. The lignin-derived methoxyphenol assemblage, dominated by vinylguaiacol and vinylsyringol derivatives in all sediments, points to large OM contribution from higher plants. The spatial distributions of PAHs (polyaromatic hydrocarbons) showed that most pollution sources were mixed sources including both pyrogenic and petrogenic. Low carbon preference indexes (CPI > 1) for n-alkanes, the presence of UCM (unresolved complex mixture) and the distribution of hopanes (C-29-C-36) and steranes (C-27-C-29) suggested localized petroleum-derived hydrocarbon inputs to the core sediments. Series of LABs were found in most sediment samples also pointing to domestic sewage anthropogenic contributions to the sediment OM.EU Erasmus Mundus Joint Doctorate fellowship (FUECA, University of Cadiz, Spain)EUEuropean Commission [FP7-ENV-2011, 282845, FP7-534 ENV-2012, 308392]MINECO project INTERCARBON [CGL2016-78937-R]info:eu-repo/semantics/publishedVersio

    The Impact of Different Root Exudate Components on Phenanthrene Availability in Soil

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    Changes in the abundance of sugars and sugar-like compounds in tall fescue (Festuca arundinacea) due to growth in naphthalene-treated sand

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    The hydrophilic metabolome of tall fescue (Festuca arundinacea) adapted to grow in naphthalene-treated sand (0.8 g kg−1 sand dw) was analysed using gas chromatography-mass spectrometry, and peaks corresponding to the more abundant compounds were tentatively identified from analysis of their mass spectral features and reference to the NIST Mass Spectral Database. Particular attention was paid to sugars as they are known to play important roles as stress regulators in plants. The results showed that the abundance of sugars was greater in the roots but lesser in the shoots of treated plants when compared to their control counterparts. The results for indole acetic acid (IAA) were notable: IAA was prominently less in the treated roots compared to shoots, and in treated shoots, IAA was particularly subdued compared to untreated shoots consistent with IAA degradation in treated plant tissues. The differences in the molecular phenotype between control and treated plants were expressed in root structural differences. The treated roots were modified to have greater suberisation, enhanced thickening in the endodermis and distortions in the cortical zone as demonstrated through scanning electron and epi-fluorescence microscopy
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