282 research outputs found

    Simulations of events for the LUX-ZEPLIN (LZ) dark matter experiment

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    The LUX-ZEPLIN dark matter search aims to achieve a sensitivity to the WIMP-nucleon spin-independent cross-section down to (1–2)×10−12 pb at a WIMP mass of 40 GeV/c2. This paper describes the simulations framework that, along with radioactivity measurements, was used to support this projection, and also to provide mock data for validating reconstruction and analysis software. Of particular note are the event generators, which allow us to model the background radiation, and the detector response physics used in the production of raw signals, which can be converted into digitized waveforms similar to data from the operational detector. Inclusion of the detector response allows us to process simulated data using the same analysis routines as developed to process the experimental data

    Novel deletion alleles carrying CYP21A1P/A2 chimeric genes in Brazilian patients with 21-hydroxylase deficiency

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    <p>Abstract</p> <p>Background</p> <p>Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by deletions, large gene conversions or mutations in <it>CYP21A2 </it>gene. The human gene is located at 6p21.3 within a <it>locus </it>containing the genes for putative serine/threonine Kinase <it>RP</it>, complement <it>C4</it>, steroid 21-hydroxylase <it>CYP21 </it>tenascin <it>TNX</it>, normally, in a duplicated cluster known as RCCX module. The <it>CYP21 </it>extra copy is a pseudogene (<it>CYP21A1P</it>). In Brazil, 30-kb deletion forming monomodular alleles that carry chimeric <it>CYP21A1P/A2 </it>genes corresponds to ~9% of disease-causing alleles. Such alleles are considered to result from unequal crossovers within the bimodular <it>C4/CYP21 locus</it>. Depending on the localization of recombination breakpoint, different alleles can be generated conferring the locus high degree of allelic variability. The purpose of the study was to investigate the variability of deleted alleles in patients with 21-hydroxylase deficiency.</p> <p>Methods</p> <p>We used different techniques to investigate the variability of 30-kb deletion alleles in patients with 21-hydroxylase deficiency. Alleles were first selected after Southern blotting. The composition of <it>CYP21A1P/A2 </it>chimeric genes was investigated by ASO-PCR and MLPA analyses followed by sequencing to refine the location of recombination breakpoints. Twenty patients carrying at least one allele with <it>C4/CYP21 </it>30-kb deletion were included in the study.</p> <p>Results</p> <p>An allele carrying a <it>CYP21A1P/A2 </it>chimeric gene was found unusually associated to a <it>C4B/C4A </it><it>Taq </it>I 6.4-kb fragment, generally associated to <it>C4B </it>and <it>CYP21A1P </it>deletions. A novel haplotype bearing both p.P34L and p.H62L, novel and rare mutations, respectively, was identified in exon 1, however p.P30L, the most frequent pseudogene-derived mutation in this exon, was absent. Four unrelated patients showed this haplotype. Absence of p.P34L in <it>CYP21A1P </it>of normal controls indicated that it is not derived from pseudogene. In addition, the combination of different approaches revealed nine haplotypes for deleted 21-hydroxylase deficiency alleles.</p> <p>Conclusions</p> <p>This study demonstrated high allelic variability for 30-kb deletion in patients with 21-hydroxylase deficiency indicating that a founder effect might be improbable for most monomodular alleles carrying <it>CYP21A1P/A2 </it>chimeric genes in Brazil.</p
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