Determination of βS haplotypes in patients with sickle-cell anemia in the state of Rio Grande do Norte, Brazil

βS haplotypes were studied in 47 non-related patients with sickle-cell anemia from the state of Rio Grande do Norte, Brazil. Molecular analysis was conducted by PCR/RFLP using restriction endonucleases XmnI, HindIII, HincII and HinfI to analyze six polymorphic sites from the beta cluster. Twenty-seven patients (57.5%) were identified with genotype CAR/CAR, 9 (19.1%) CAR/BEN, 6 (12.8%) CAR/CAM, 1 (2.1%) BEN/BEN, 2 (4.3%) CAR/Atp, 1 (2.1%) BEN/Atp and 1 (2.1%) with genotype Atp/Atp. The greater frequency of Cameroon haplotypes compared to other Brazilian states suggests the existence of a peculiarity of African origin in the state of Rio Grande do Norte

Identification and rejection of pile-up jets at high pseudorapidity with the ATLAS detector

The rejection of forward jets originating from additional proton–proton interactions (pile-up) is crucial for a variety of physics analyses at the LHC, including Standard Model measurements and searches for physics beyond the Standard Model. The identification of such jets is challenging due to the lack of track and vertex information in the pseudorapidity range |η| > 2.5. This paper presents a novel strategy for forward pile-up jet tagging that exploits jet shapes and topological jet correlations in pile-up interactions. Measurements of the per-jet tagging efficiency are presented using a data set of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of 13 TeV collected with the ATLAS detector. The fraction of pile-up jets rejected in the range 2.5 < |η| < 4.5 is estimated in simulated events with an average of 22 interactions per bunch-crossing. It increases with jet transverse momentum and, for jets with transverse momentum between 20 and 50 GeV, it ranges between 49% and 67% with an efficiency of 85% for selecting hard-scatter jets. A case study is performed in Higgs boson production via the vector-boson fusion process, showing that these techniques mitigate the background growth due to additional proton–proton interactions, thus enhancing the reach for such signatures

Paucimorphic alleles versus polymorphic alleles and rare mutations in disease causation: Theory, observation and detection

Definitions of polymorphism in a gene include occurrence of a rarer allele of at least 1% frequency; or occurrence of the commonest allele at less than 95% frequency. Many alleles of single nucleotide polymorphisms (SNPs) in genes occur at much higher frequency (up to 50%). Many common diseases have a substantial genetic component. The prevailing hypothesis for the molecular basis of common diseases is that it involves the combinatoric action of common polymorphic alleles of minor effect (common disease / common variant, CD / CV hypothesis). The ready development of genome-wide databases of high frequency SNPs is enabling the testing of this hypothesis. A contrasting approach has been the study of very highly selected cases and families by linkage and mutation detection techniques to identify rare mutations of large effect on a gene, often private to a single family (rare disease / rare variant, RD / RV hypothesis. These approaches have formed the mainstay of disease gene discovery, the latter having been feasible for a decade, the former just now becoming feasible. However, an intermediate possibility exists. Sequence changes at an intermediate frequency (herewith, “paucimorphisms”, arbitrarily 0.0005<q<0.05) may exist and may have a moderate effect. A number of different loci may predispose to the same disease, although only one paucimorphic allele of one particular gene will be found in any one individual. Exploring the “paucimorphisms hypothesis” will require mutation detection applied both at the level of large numbers of relatively unselected cases and at the population level. In this review we consider the foundations of this hypothesis, relevant available technologies and possible future approaches to systematically explore this hypothesis

Transcranial doppler in sickle cell anaemia: evaluation of brain blood flow parameters in children of Aracaju, Northeast - Brazil Doppler transcraniano em portadores de anemia falciforme: estudo dos parâmetros de fluxo sangüíneo cerebral em crianças de Aracaju, Sergipe

BACKGROUND: Environmental factors interfere on sickle cell anaemia (SCA). Transcanial Doppler (TCD) is important to evaluate cerebrovascular disease. OBJECTIVE: To evaluate brain haemodynamic profile of children with SCA in Sergipe. METHODS: Cross sectional study (group1: SCA patients aged 3-18; group2: age and sex matched healthy individuals). Baseline brain flow was evaluated. RESULTS: Group1=34 patients; group 2=81 controls. SCA patients had mean velocity (MV)=125.69 cm/s±23.40; pulsatility index (PI)=0.66±0.10; middle cerebral artery ratio (MCAr)=14.53±15.23; right anterior cerebral artery/right middle cerebral artery=0.77±0.20; left anterior cerebral artery/left middle cerebral artery=0.78±0.20. Controls had MV=79.44±15.54; PI=0.82±0.11; MCAr=13.19±13.77; right anterior cerebral artery/right middle cerebral artery=0.80±0.16; left anterior cerebral artery/left middle cerebral artery=0.84±0.18. MV and PI differences were statistically significant between groups. MV was related to age but not to gender. CONCLUSION: MV evaluation using TCD was similar to international standards and possible to be used in our setting.<br>INTRODUÇÃO: Aspectos ambientais interferem na apresentação da anemia falciforme (AF). Doppler transcraniano (DTC) é útil na avaliação do risco para doença cerebrovascular em pacientes com AF. OBJETIVO: Avaliar o perfil hemodinâmico cerebral de crianças com AF em Sergipe. MÉTODO: Estudo transversal (grupo1: portadores de AF 3-18 anos; grupo2: indivíduos saudáveis, pareados por idade e gênero). Foram avaliadas medidas de fluxo sangüíneo cerebral basal. RESULTADOS: Grupo1 (n=34): velocidade média (Vm)=125,69 cm/s ±23,40; índice de pulsatilidade (Ip)=0,66±0,10; relação entre artéria cerebral média (ACMs)=14,53±15,23; artéria cerebral anterior (ACA)/ACM direita=0,77±0,20; ACA/ACM esquerda=0,78±0,20. Grupo 2 (n=81): Vm=79,44 cm/s ±15,54; Ip=0,82±0,11, relação entre ACMs=13,19±13,77, ACA/ACM direita=0,80±0,16; ACA/ACM esquerda=0,84± 0,18. Vm foi maior e Ip menor no grupo1. Vm se correlacionou com idade mas não com gênero. CONCLUSÃO: O perfil hemodinâmico cerebral de crianças com AF em Sergipe assemelha-se às referências internacionais. Não se observou interferência de fatores ambientais sobre os resultados

Genetic relationships among native americans based on beta-globin gene cluster haplotype frequencies

The distribution of b-globin gene haplotypes was studied in 209 Amerindians from eight tribes of the Brazilian Amazon: Asurini from Xingú, Awá-Guajá, Parakanã, Urubú-Kaapór, Zoé, Kayapó (Xikrin from the Bacajá village), Katuena, and Tiriyó. Nine different haplotypes were found, two of which (n. 11 and 13) had not been previously identified in Brazilian indigenous populations. Haplotype 2 (+ - - - -) was the most common in all groups studied, with frequencies varying from 70% to 100%, followed by haplotype 6 (- + + - +), with frequencies between 7% and 18%. The frequency distribution of the b-globin gene haplotypes in the eighteen Brazilian Amerindian populations studied to date is characterized by a reduced number of haplotypes (average of 3.5) and low levels of heterozygosity and intrapopulational differentiation, with a single clearly predominant haplotype in most tribes (haplotype 2). The Parakanã, Urubú-Kaapór, Tiriyó and Xavante tribes constitute exceptions, presenting at least four haplotypes with relatively high frequencies. The closest genetic relationships were observed between the Brazilian and the Colombian Amerindians (Wayuu, Kamsa and Inga), and, to a lesser extent, with the Huichol of Mexico. North-American Amerindians are more differentiated and clearly separated from all other tribes, except the Xavante, from Brazil, and the Mapuche, from Argentina. A restricted pool of ancestral haplotypes may explain the low diversity observed among most present-day Brazilian and Colombian Amerindian groups, while interethnic admixture could be the most important factor to explain the high number of haplotypes and high levels of diversity observed in some South-American and most North-American tribes