Camperdown Hemoglobin Associated With β° Thalassemia In A Brazilian Child

We report the coexistence of Hb Camperdown [β 104 (G6) Arg → Ser] and β°-thalassemia [β39 (Gln → stop codon)] in a nine-month-old Brazilian boy. He had a relatively more severe hypochromic and microcytic anemia in comparison to his mother's β-thalassemia trait. His Hb Camperdown heterozygous father was clinically and hematologically normal. To our knowledge, this is the first description of an association of β°-thalassemia with Hb Camperdown. Copyright by the Brazilian Society of Genetics.283394396Araújo, A.S., Silva, W.A., Leao, S.A., Bandeira, F.C., Petrou, M., Modell, B., Zago, M.A., A different molecular pattern of β-thalassemia mutations in Northeast of Brazil (2003) Hemoglobin, 27, pp. 211-217Amone, A., X-ray diffraction study of binding of 2,3-diphosphoglycerate to human deoxyhemoglobin (1972) Nature, 237, pp. 146-149Bertuzzo, C.S., Sonati, M.F., Costa, F.F., Hematological phenotype and the type of β thalassemia mutation in Brazil (1997) Braz J Genet, 20, pp. 319-321Bianco, I., Graziani, B., Carboni, C., Genetic patterns in thalassemia intermedia (constitutional microcytic anemia). Familial hematological and biosynthetic studies (1977) Hum Hered, 27, pp. 257-272Blouquit, Y., Lacombe, C., Arous, N., Le Qurrec, A., Branconnier, F., Bonhomme, J., Soummer, A.M., Galacteros, F., Seven new cases of hemoglobin Camperdown alpha 2 beta 2 104 (G6) ARG → SER found in Malta, Sicily and Tunisia (1984) Hemoglobin, 8, pp. 613-619Chang, J.C., Kan, Y.W., β°-thalassemia, a nonsense mutation in man (1979) Proc Natl Acad Sci USA, 76, pp. 2886-2889Clarke, G.M., Higgins, T.N., Laboratory investigation of hemoglobinopathies and thalassemias: Review and update (2000) Clin Chem, 46, pp. 1284-1290Fonseca, S.F., Kerbauy, J., Escrivçao, C., Figueiredo, M.S., Cançado, R., Arruda, V.R., Saad, S.T.O., Costa, F.F., Genetic analysis of beta-thalassemia major and beta-thalassemia intermedia in Brazil (1998) Hemoglobin, 22, pp. 197-207Grignoli, C.R.E., Carvalho, M.H., Kimura, E.M., Sonati, M.F., Arruda, V.R., Saad, S.T.O., Costa, F.F., β°-thalassemia resulting from a novel mutation: β66/u → stop codon (2000) Eur J Haematol, 64, pp. 137-138Kimura, E.M., Grignoli, C.R.E., Pinheiro, V.R.P., Costa, F.F., Sonati, M.F., Thalassemia intermedia as a result of heterozygosis for β°-thallassemia and αααanti3.7/αα genotype in a Brazilian patient (2003) Braz J Med Biol Res, 36, pp. 699-701Kister, J., Barbadjian, J., Blouquit, Y., Bohn, B., Galacteros, F., Poyart, C., Inhibition of oxygen-linked anion binding in Hb Camperdown [α2β2 104 (G6) ARG → SER] (1989) Hemoglobin, 13, pp. 567-578Miranda, S.R.P., Kimura, E.M., Teixeira, R.C., Bertuzzo, C.S., Ramalho, A.A., Saad, S.T.O., Costa, F.F., Hb Camperdown [α2β2 104 (G6) ARG → SER] identified by DNA analysis in a Brazilian family (1996) Hemoglobin, 20, pp. 147-153Old, J.M., Screening arid genetic diagnosis of haemoglobin disorders (2003) Blood Rev, 17, pp. 43-53Olivieri, N.F., The β-thalassemias (1999) N Engl J Med, 341, pp. 99-109Thein, S.L., Genetic insights into the clinical diversity of beta thalassaemia (2004) Br J Haematol, 124, pp. 264-274Weatherall, D.J., Clegg, J.B., Inherited haemoglobin disorders: An increasing global health problem (2001) Bull World Health Organ, 79, pp. 704-712Wilkinson, T., Chua, C.G., Carrell, R.W., Robin, H., Exner, T., Lee, K.M., Kronenberg, H., Haemoglobin Camperdown β 104(G6) Arginine leads to serine (1975) Biochim Biophys Acta, 393, pp. 195-200Zago, M.A., Costa, F.F., Hereditary hemoglobin disorders in Brazil (1985) Trans R Soc Trop Med Hyg, 79, pp. 385-38

Genomic analysis of two phlebotomine sand fly vectors of Leishmania from the New and Old World.

Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the kinetoplastid parasites of the genus Leishmania, the causative agents of devastating diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. No approved efficacious vaccine exists for leishmaniasis and available therapeutic drugs are either toxic and/or expensive, or the parasites are becoming resistant to the more recently developed drugs. Therefore, sand fly and/or reservoir control are currently the most effective strategies to break transmission. To better understand the biology of sand flies, including the mechanisms involved in their vectorial capacity, insecticide resistance, and population structures we sequenced the genomes of two geographically widespread and important sand fly vector species: Phlebotomus papatasi, a vector of Leishmania parasites that cause cutaneous leishmaniasis, (distributed in Europe, the Middle East and North Africa) and Lutzomyia longipalpis, a vector of Leishmania parasites that cause visceral leishmaniasis (distributed across Central and South America). We categorized and curated genes involved in processes important to their roles as disease vectors, including chemosensation, blood feeding, circadian rhythm, immunity, and detoxification, as well as mobile genetic elements. We also defined gene orthology and observed micro-synteny among the genomes. Finally, we present the genetic diversity and population structure of these species in their respective geographical areas. These genomes will be a foundation on which to base future efforts to prevent vector-borne transmission of Leishmania parasites

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

A search for resonances decaying into a Higgs boson and a new particle X in the XH → qqbb final state with the ATLAS detector

A search for heavy resonances decaying into a Higgs boson (H) and a new particle (X) is reported, utilizing 36.1 fb−1 of proton–proton collision data at collected during 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider. The particle X is assumed to decay to a pair of light quarks, and the fully hadronic final state is analysed. The search considers the regime of high XH resonance masses, where the X and H bosons are both highly Lorentz-boosted and are each reconstructed using a single jet with large radius parameter. A two-dimensional phase space of XH mass versus X mass is scanned for evidence of a signal, over a range of XH resonance mass values between 1 TeV and 4 TeV, and for X particles with masses from 50 GeV to 1000 GeV. All search results are consistent with the expectations for the background due to Standard Model processes, and 95% CL upper limits are set, as a function of XH and X masses, on the production cross-section of the resonance

Measurement of the cross section for isolated-photon plus jet production in pp collisions at √s=13 TeV using the ATLAS detector

The dynamics of isolated-photon production in association with a jet in proton–proton collisions at a centre-of-mass energy of 13 TeV are studied with the ATLAS detector at the LHC using a dataset with an integrated luminosity of 3.2 fb−1. Photons are required to have transverse energies above 125 GeV. Jets are identified using the anti- algorithm with radius parameter and required to have transverse momenta above 100 GeV. Measurements of isolated-photon plus jet cross sections are presented as functions of the leading-photon transverse energy, the leading-jet transverse momentum, the azimuthal angular separation between the photon and the jet, the photon–jet invariant mass and the scattering angle in the photon–jet centre-of-mass system. Tree-level plus parton-shower predictions from Sherpa and Pythia as well as next-to-leading-order QCD predictions from Jetphox and Sherpa are compared to the measurements