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‣ Evolução cromossômica: estudo da variabilidade cariotípica em Platyrrhini e das homeologias e sintenias com cromossomos humanos; Chromosome evolution: Karyotype variability in Platyrrhini and studies of sinteny and homologies between human chromosomes

Iughetti, Cristiani Gifalli
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 29/09/2008 Português
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Estudamos os cariótipos de espécimes de macacos brasileiros (Platyrrhini, Primates) com técnicas citogenéticas tradicionais e de FISH com as sondas totais dos cromossomos 14, 15 e X humanos e do cromossomo Y de Brachyteles arachnoides obtida por microdissecção cromossômica. Vinte e quatro espécimes de Alouatta guariba clamitans, doze machos e doze fêmeas foram estudados. Para os machos, encontramos um número diplóide de 2n = 49, devido à ausência aparente do cromossomo Y provavelmente decorrente de uma translocação Y-autossomo, e 2n = 46 cromossomos, com variação nas fórmulas cromossômicas com 17, 19, 20, 21 ou 24 cromossomos metacêntricos ou submetacêntricos e 22, 28, 29, 30 ou 32 acrocêntricos. Para as fêmeas, uma variabilidade maior no número diplóide foi observada com 46, 48 e 50 cromossomos e as fórmulas cromossômicas encontradas mostraram 18, 19, 20, 21, 27 ou 28 cromossomos metacêntricos ou submetacêntricos e 18, 19, 27, 30, 31 e 32 acrocêntricos. Os cromossomos X eram submetacêntricos. Pares heteromórficos foram observados. Uma fêmea com 48 cromossomos foi descrita pela primeira vez, este número diplóide só havia sido descrito em um único exemplar macho. A confirmação da subespécie dos indivíduos analisados se deu pela presença do par cromossômico característico de Alouatta guariba clamitans...

‣ Apresentações clínicas não usuais de pacientes portadores de síndrome de Patau e Edwards : um desafio diagnóstico?; Unusual clinical presentations of patients with Patau and Edwards syndromes : a diagnostic challenge?

Zen, Paulo Ricardo Gazzola; Rosa, Rafael Fabiano Machado; Rosa, Rosana Cardoso Manique; Dalle Mulle, Josiane; Graziadio, Carla; Paskulin, Giorgio Adriano
Fonte: Universidade Federal do Rio Grande do Sul Publicador: Universidade Federal do Rio Grande do Sul
Tipo: Artigo de Revista Científica Formato: application/pdf
Português
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Objetivo: Relatar dois pacientes, um acometido por trisso¬mia do cromossomo 13 em mosaico e outro por trissomia do cro¬mossomo 18, ambos com apresentações clínicas não usuais. Descrição do caso: Paciente do sexo feminino de dois meses de idade, que apresentava deficiência de crescimento, dismorfias menores de face e de membros, paresia facial uni¬lateral, cardiopatia congênita, hipotonia e evolução com o surgimento de manchas hipocrômicas e atraso do desenvolvi¬mento neuropsicomotor. O segundo caso é de um paciente do sexo masculino, com 19 dias de vida, que também mostrava deficiência de crescimento, anomalias faciais menores, defeito radial, cardiopatia congênita e hipertonia. Os cariótipos por bandas GTG confirmaram o diagnóstico, respectivamente, de síndromes de Patau e de Edwards. Comentários: Os presentes relatos têm por objetivo alertar os pediatras sobre manifestações não usuais nas tris¬somias dos cromossomos 13 e 18, as quais podem dificultar a suspeita diagnóstica.; Objective: Report two patients, one with trisomy 13 mosaicism and the other with trisomy 18, both with unusual clinical presentations. Case description: The first case was a female patient with two months of age who presented growth deficiency...

‣ Craniofacial abnormalities among patients with Edwards Syndrome

Rosa,Rafael Fabiano M.; Rosa,Rosana Cardoso M.; Lorenzen,Marina Boff; Zen,Paulo Ricardo G.; Graziadio,Carla; Paskulin,Giorgio Adriano
Fonte: Sociedade de Pediatria de São Paulo Publicador: Sociedade de Pediatria de São Paulo
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/2013 Português
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OBJECTIVE To determine the frequency and types of craniofacial abnormalities observed in patients with trisomy 18 or Edwards syndrome (ES). METHODS This descriptive and retrospective study of a case series included all patients diagnosed with ES in a Clinical Genetics Service of a reference hospital in Southern Brazil from 1975 to 2008. The results of the karyotypic analysis, along with clinical data, were collected from medical records. RESULTS: The sample consisted of 50 patients, of which 66% were female. The median age at first evaluation was 14 days. Regarding the karyotypes, full trisomy of chromosome 18 was the main alteration (90%). Mosaicism was observed in 10%. The main craniofacial abnormalities were: microretrognathia (76%), abnormalities of the ear helix/dysplastic ears (70%), prominent occiput (52%), posteriorly rotated (46%) and low set ears (44%), and short palpebral fissures/blepharophimosis (46%). Other uncommon - but relevant - abnormalities included: microtia (18%), orofacial clefts (12%), preauricular tags (10%), facial palsy (4%), encephalocele (4%), absence of external auditory canal (2%) and asymmetric face (2%). One patient had an initial suspicion of oculo-auriculo-vertebral spectrum (OAVS) or Goldenhar syndrome. CONCLUSIONS: Despite the literature description of a characteristic clinical presentation for ES...

‣ Retrospective cohort of trisomy 18 (Edwards syndrome) in southern Brazil

Denardin,Daniela; Savaris,Fabíola Elizabete; Cunha,André Campos da; Betat,Rosilene da Silveira; Telles,Jorge Alberto Bianchi; Targa,Luciano Vieira; Weiss,Aline; Zen,Paulo Ricardo Gazzola; Rosa,Rafael Fabiano Machado
Fonte: Associação Paulista de Medicina - APM Publicador: Associação Paulista de Medicina - APM
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2014 Português
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CONTEXT AND OBJECTIVE: Trisomy 18 (T18), or Edwards syndrome, is a chromosomal disease characterized by a broad clinical picture and a poor prognosis. Our aim was to describe clinical, radiological and survival data of a cohort of patients prenatally diagnosed with T18. DESIGN AND SETTING: Retrospective single cohort in the Fetal Medicine Service of Hospital Materno Infantil Presidente Vargas (HMIPV). METHODS: All sequential patients with T18 registered at the Fetal Medicine Service of HMIPV between January 2005 and September 2013 were considered. We gathered their clinical, radiological and survival data and used the Kaplan-Meier test for survival analysis. RESULTS: Ten patients were diagnosed with T18, of whom seven (70%) were female. The majority (90%) were referred due to malformations seen on ultrasound. The mean gestational age at the first evaluation was 25.5 weeks. At karyotyping, the defects were considered multiple in only four patients (40%). All the fetuses presented full trisomy of chromosome 18. The main abnormality observed was congenital heart disease (n = 7). Intrauterine death occurred in half of the patients (50%). All live patients (n = 5) were born through cesarean section presenting low weight and low Apgar scores. The median length of survival after birth was 18 days. CONCLUSIONS: T18 is associated with a high risk of fetal and neonatal death. The majority of the patients present major malformations identified through ultrasound...

‣ Genomewide Scan for Linkage Reveals Evidence of Several Susceptibility Loci for Alopecia Areata

Martinez-Mir, Amalia ; Zlotogorski, Abraham ; Gordon, Derek ; Petukhova, Lynn ; Mo, Jianhong ; Gilliam, T. Conrad ; Londono, Douglas ; Haynes, Chad ; Ott, Jurg ; Hordinsky, Maria ; Nanova, Krassimira ; Norris, David ; Price, Vera ; Duvic, Ma
Fonte: The American Society of Human Genetics Publicador: The American Society of Human Genetics
Tipo: Artigo de Revista Científica
Português
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Alopecia areata (AA) is a genetically determined, immune-mediated disorder of the hair follicle that affects 1%–2% of the U.S. population. It is defined by a spectrum of severity that ranges from patchy localized hair loss on the scalp to the complete absence of hair everywhere on the body. In an effort to define the genetic basis of AA, we performed a genomewide search for linkage in 20 families with AA consisting of 102 affected and 118 unaffected individuals from the United States and Israel. Our analysis revealed evidence of at least four susceptibility loci on chromosomes 6, 10, 16 and 18, by use of several different statistical approaches. Fine-mapping analysis with additional families yielded a maximum multipoint LOD score of 3.93 on chromosome 18, a two-point affected sib pair (ASP) LOD score of 3.11 on chromosome 16, several ASP LOD scores >2.00 on chromosome 6q, and a haplotype-based relative risk LOD of 2.00 on chromosome 6p (in the major histocompatibility complex locus). Our findings confirm previous studies of association of the human leukocyte antigen locus with human AA, as well as the C3H-HeJ mouse model for AA. Interestingly, the major loci on chromosomes 16 and 18 coincide with loci for psoriasis reported elsewhere. These results suggest that these regions may harbor gene(s) involved in a number of different skin and hair disorders.

‣ Molecular Characterization of a Nonneuronal Human Unc18 Homolog

Ziegler, S.; Mortrud, M.; Swartz, A.; Baker, E.; Sutherland, G.; Burmeister, M.; Mulligan, J.
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Artigo de Revista Científica
Publicado em //1996 Português
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A cDNA clone encoding a human homolog of the Caenorhabditis elegans unc-18 gene was identified following random sequencing of clones from IL-2-activated human NK cells. This cDNA clone is related to the nonneuronal Munc-18b and so has been called Hunc-18b. The Hunc-18b transcripts were found in most human tissues, with the exception of brain and skeletal muscle, and in cells from all lymphoid lineages. The Hunc-18b gene was localized to human chromosome 19p13.2-p13.3, and the mouse homolog, Munc-18b, was mapped to the proximal region of mouse Chromosome 8.

‣ CAG repeat expansion in autosomal dominant familial spastic paraparesis - novel expansion in a subset of patients

Benson, K.; Horwitz, M.; Wolff, J.; Friend, K.; Thompson, E.; White, S.; Richards, R.; Raskind, W.; Bird, T.
Fonte: OXFORD UNIV PRESS Publicador: OXFORD UNIV PRESS
Tipo: Artigo de Revista Científica
Publicado em //1998 Português
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Autosomal dominant familial spastic paraplegia (FSP) is a genetically heterogeneous neurodegenerative disorder displaying anticipation for which three loci have been mapped to the chromosomal positions 14q11.2-q24.3 (SPG3), 2p21-p24 (SPG4) and 15q11.1 (SPG6). The repeat expansion detection (RED) method has been used to demonstrate expanded CAG repeats in some FSP families that map to SPG4. We analyzed 20 FSP families, including four for which there is evidence for linkage to SPG4, and found that in most cases the repeat expansion detected by RED is due to non-pathogenic expansions of the chromosome 18q21.1 SEF2-1 or 17q21.3 ERDA1 locus. Polymorphic expansions at SEF2-1 and ERDA1 appear frequent and may confound RED studies in the search for genes causing disorders demonstrating anticipation. In six FSP families, however, CAG repeat expansion was detected in a subset of affected and at-risk individuals that did not result from expansion of the SEF2-1 and ERDA1 loci. Overall, 11 of 37 (30%) of the FSP patients with a CAG/CTG repeat expansion are unaccounted for by the SEF2-1 and ERDA1 loci, compared with two of 23 (9%) of the unaffected at-risk individuals and none of 19 controls. In the majority of cases these novel expansions were shorter than those previously reported.

‣ Construction of an ~700-kb transcript map around the Familial Mediterranean Fever locus on human chromosome 16p13.3

Centola, M.; Chen, X.; Sood, R.; Deng, Z.; Aksentijevich, I.; Blake, T.; Ricke, D.; Chen, X.; Wood, G.; Zaks, N.; Richards, N.; Krizman, D.; Mansfield, E.; Apostolou, S.; Liu, J.; Shafran, N.; Vedula, A.; Hamon, M.; Cercek, A.; Kahan, T.; et al.
Fonte: COLD SPRING HARBOR LAB PRESS Publicador: COLD SPRING HARBOR LAB PRESS
Tipo: Artigo de Revista Científica
Publicado em //1998 Português
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We used a combination of cDNA selection, exon amplification, and computational prediction from genomic sequence to isolate transcribed sequences from genomic DNA surrounding the familial Mediterranean fever (FMF) locus. Eighty-seven kb of genomic DNA around D16S3370, a marker showing a high degree of linkage disequilibrium with FMF, was sequenced to completion, and the sequence annotated. A transcript map reflecting the minimal number of genes encoded within the ∼700 kb of genomic DNA surrounding the FMF locus was assembled. This map consists of 27 genes with discreet messages detectable on Northerns, in addition to three olfactory-receptor genes, a cluster of 18 tRNA genes, and two putative transcriptional units that have typical intron–exon splice junctions yet do not detect messages on Northerns. Four of the transcripts are identical to genes described previously, seven have been independently identified by the French FMF Consortium, and the others are novel. Six related zinc-finger genes, a cluster of tRNAs, and three olfactory receptors account for the majority of transcribed sequences isolated from a 315-kb FMF central region (betweenD16S468/D16S3070 and cosmid 377A12). Interspersed among them are several genes that may be important in inflammation. This transcript map not only has permitted the identification of the FMF gene (MEFV)...

‣ Localisation of human cadherin genes to chromosome regions exhibiting cancer-related loss of heterozygosity.

Kremmidiotis, G.; Baker, E.; Crawford, J.; Eyre, H.; Nahmias, J.; Callen, D.
Fonte: ACADEMIC PRESS INC ELSEVIER SCIENCE Publicador: ACADEMIC PRESS INC ELSEVIER SCIENCE
Tipo: Artigo de Revista Científica
Publicado em //1998 Português
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This report presents the chromosomal localization of cadherin genes. Cadherins are cellular adhesion molecules. Since disturbance of intracellular adhesion is important for invasion and metastasis of tumor cells, cadherins are considered prime candidates for tumor suppressor genes. A variety of solid tumors show loss of heterozygosity of the long arm of chromosome 16, which is indicative of the potential location of tumor suppressor genes. Refined and new localizations of six cadherin genes (CDH3, 5, 8, 11, 13, and 15) to the long arm of chromosome 16 are shown. CDH15 was localized to 16q24.3, in a region that exhibits loss of heterozygosity in a number of sporadic breast cancer tumors. Previous localization of CDH13 (H-cadherin) to 16q24 suggested this gene as a tumor suppressor candidate in the 16q24.3 loss of heterozygosity region; however, refined mapping presented in this report localizes CDH13 proximal to this region. A human EST homologous to the chicken cadherin-7 was partially sequenced and found to represent a new human cadherin. This cadherin mapped to chromosome 18q22-q23, a region that exhibits loss of heterozygosity in head and neck squamous cell carcinomas. CDH16 was localized to 8q22.1, a region exhibiting loss of heterozygosity in adult acute myeloid leukemia.

‣ Chromosomal localisation of the human P2y6 purinoceptor gene and phylogenetic analysis of the P2y purinoceptor family

Somers, G.; Hammet, F.; Woollatt, E.; Richards, R.; Southey, M.; Venter, D.
Fonte: Academic Press Publicador: Academic Press
Tipo: Artigo de Revista Científica
Publicado em //1997 Português
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The G-protein-coupled P2Y purinoceptors mediate a variety of physiological effects in response to extracellular nucleotides. With the recent discovery of several new members from a variety of species, the P2Y purinoceptor family now encompasses types P2Y1to P2Y8. By fluorescencein situhybridization and utilization of the National Center for Biotechnology Information (NCBI) database, the human P2Y6gene was localized to chromosome 11q13.5, between polymorphic markers D11S1314 and D11S916. NCBI database analysis of the remaining human P2Y purinoceptor genes revealed that P2Y2and P2Y6mapped to within less than 4 cM, and thus constitute the first described chromosomal clustering of this gene family. Phylogenetic analysis of the P2Y purinoceptor family demonstrated the presence of five evolutionary branches and suggests the occurrence of an ancient gene duplication event.; Gino R. Somers, Fleur Hammet, Erica Woollatt, Robert I. Richards, Melissa C. Southey and Deon J. Venter; Available online 18 April 2002

‣ Comparative analysis of the phosphomannomutase genes PMM1, PMM2 and PMM2y: the sequence variation in the processed pseudogene is a reflection of the mutations found in the functional gene.

Schollen, E.; Pardon, E.; Heykants, L.; Renard, J.P.; Doggett, N.; Callen, D.; Cassiman, J.J.; Matthijs, G.
Fonte: OXFORD UNIV PRESS Publicador: OXFORD UNIV PRESS
Tipo: Artigo de Revista Científica
Publicado em //1998 Português
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The search for the carbohydrate-deficient glycoprotein syndrome type I (CDG1) gene has revealed the existence of a family of phosphomannomutase (PMM) genes in humans. Two expressed PMM genes, PMM1 and PMM2 , are located on chromosome bands 22q13 and 16p13, respectively, and a processed pseudogene PMM2 psi is located on chromosome 18p. Mutations in PMM2 are the cause of CDG type IA whereas no disorder has been associated with defects in PMM1 as yet. Here, we describe the genomic organization of these paralogous genes. There is a 65% identity of the coding sequence, and all intron/exon boundaries have been conserved. The processed pseudogene is more closely related to PMM2 . Remarkably, several base substitutions in PMM2 that are associated with disease are also present at the corresponding positions in the pseudogene. Thus, mutations that occur at a slow rate in the active gene in the population have also accumulated in the pseudogene.

‣ NEDD4-2 as a potential candidate susceptibility gene for epileptic photosensitivity

Dibbens, L.; Ekberg, J.; Taylor, I.; Hodgson, B.; Conroy, S.J.; Lensink, I.; Kumar, S.; Zielinski, M.; Harkin, L.; Sutherland, G.; Adams, D.; Berkovic, S.; Scheffer, I.; Mulley, J.; Poronnik, P.
Fonte: Blackwell Munksgaard Publicador: Blackwell Munksgaard
Tipo: Artigo de Revista Científica
Publicado em //2007 Português
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Photosensitive seizures occur most commonly in childhood and adolescence, usually as a manifestation of complex idiopathic generalized epilepsies (IGEs). Molecular mechanisms underlying this condition are yet to be determined because no susceptibility genes have been identified. The NEDD4-2 (Neuronally Expressed Developmentally Downregulated 4) gene encodes a ubiquitin protein ligase proposed to regulate cell surface levels of several ion channels, receptors and transporters involved in regulating neuronal excitability, including voltage-gated sodium channels (VGSCs), the most clinically relevant of the epilepsy genes. The regulation of NEDD4-2 in vivo involves complex interactions with accessory proteins in a cell type specific manner. We screened NEDD4-2 for mutations in a cohort of 253 families with IGEs. We identified three NEDD4-2 missense changes in highly conserved residues; S233L, E271A and H515P in families with photosensitive generalized epilepsy. The NEDD4-2 variants were as effective as wild-type NEDD4-2 in downregulating the VGSC subtype Nav1.2 when assessed in the Xenopus oocyte heterologous expression system showing that the direct interaction with the ion channel was not altered by these variants. These data raise the possibility that photosensitive epilepsy may arise from defective interaction of NEDD4-2 with as yet unidentified accessory or target proteins.; L. M. Dibbens...

‣ A genome-wide association scan for asthma in a general Australian population

Hui, J.; Oka, A.; James, A.; Palmer, L.; Musk, A.; Beilby, J.; Inoko, H.
Fonte: Springer Publicador: Springer
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
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To date, almost every chromosome has been implicated in genetic susceptibility to asthma to some degree. When compared with single nucleotide polymorphism, microsatellite markers exhibit high levels of heterozygosity and therefore provide higher statistical power in association. The objective of this study was to perform a genome-wide association study using 23,465 in-house microsatellite markers to detect asthma susceptibility regions in the Busselton population. In this study, three separate pooled DNA screenings yielded 18 markers with significantly different estimated frequencies in the three separate "case and control" pools: each pool consisting of 60 males and 60 females. These markers were evaluated by individual typing in 360 cases and 360 controls. Two markers showed significant differences between cases and controls (P = 0.001 and P = 0.003). Regions surrounding the two markers were subjected to high-density association mapping with a total of 14 additional markers. We were able to confirm and fine map the association in these two regions by typing 14 additional microsatellite markers (1805A09 (D18S0325i), P = 0.002; 1806D05 (D18S0181i), P = 0.001). Each region contains a predicted gene that showed strong associations with asthma. Further studies are underway to characterize the novel candidate asthma susceptibility genes identified in this genome-wide study.; J. Hui...

‣ Variants near CCNL1/LEKR1 and in ADCY5 and fetal growth characteristics in different trimesters

Mook-Kanamori, D.; Marsh, J.; Warrington, N.; Taal, H.; Newnham, J.; Beilin, L.; Lye, S.; Palmer, L.; Hofman, A.; Steegers, E.; Pennell, C.; Early Growth Genetics; Jaddoe, V.
Fonte: Endocrine Society Publicador: Endocrine Society
Tipo: Artigo de Revista Científica
Publicado em //2011 Português
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Common variants near CCNL1/LEKR1 and in ADCY5 are associated with symmetric and asymmetric fetal growth restriction, respectively. CONTEXT: A recent genome-wide association study identified variants near CCNL1/LEKR1 (rs900400) and in ADCY5 (rs9883204) to be associated with birth weight. We examined the associations of these variants with fetal growth characteristics in different trimesters, with a main interest in the timing of the associations and the affected body proportions. METHODS: We used data from two prospective cohort studies from fetal life onward in The Netherlands and Australia. Repeated fetal ultrasound examinations were performed to measure head circumference (HC), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW). Analyses were based on a total group of 3909 subjects. RESULTS: The C-allele of rs900400 was associated in second trimester with smaller fetal HC and FL, and in third trimester with smaller HC, AC, FL, and EFW. For each C-allele, the combined effect estimate for EFW in third trimester was −18.6 g (95% confidence interval, −27.5, −9.7 g; P = 4.2 × 10−5). The C-allele of rs9883204 was not associated with fetal growth characteristics in second trimester but was associated with restriction of all growth characteristics...

‣ Descripción de un caso de síndrome del comosoma 18q-

Bajo González, Tamara
Fonte: Universidade de Alcalá Publicador: Universidade de Alcalá
Tipo: Trabalho de Conclusão de Curso Formato: application/pdf
Português
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Se presenta el estudio de un caso clínico de la deleción terminal del brazo largo del cromosoma 18, también llamado Síndrome de Grouchy, en una niña de siete años de edad. Está clasificada como una enfermedad rara por tener una tasa de incidencia menor o igual a 1 de cada 2000 habitantes de la población. Se analizan los principales problemas que refieren las familias con algún miembro con una enfermedad rara, siendo el más relevante la falta de información y de medios por parte de los sistemas sanitarios público y privado. Se proponen iniciativas para la mejora de la coordinación interdisciplinar y se facilita información útil a fisioterapeutas y otros profesionales que traten a estos pacientes.; A research about a clinical case of a seven-year-old child with chromosome 18 long arm terminal deletion, also called de Grouchy syndrome, is presented. It is classified as a rare disease for having a rate less than or equal to 1 of every 2000 thousand habitants of the population. The main problems the families with a member with a rare disease refer to are analyzed, being especially relevant the lack of information and media by the public and private health systems. Initiatives regarding the better interdisciplinary coordination and useful information for physical therapists and other professionals that treat these patients are proposed.; Grado en Fisioterapia

‣ Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function

Tang, W.; Kowgier, M.; Loth, D.W.; Soler Artigas, M.; Joubert, B.R.; Hodge, E.; Gharib, S.A.; Smith, A.V.; Ruczinski, I.; Gudnason, V.; Mathias, R.A.; Harris, T.B.; Hansel, N.N.; Launer, L.J.; Barnes, K.C.; Hansen, J.G.; Albrecht, E.; Aldrich, M.C.; Aller
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
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BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16...

‣ Perinatal management of trisomy 18: a survey of obstetricians in Australia, New Zealand and the UK

Wilkinson, D.; de Crespigny, L.; Lees, C.; Savulescu, J.; Thiele, P.; Tran, T.; Watkins, A.
Fonte: John Wiley & Sons Publicador: John Wiley & Sons
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
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OBJECTIVE The objective of this study was to explore the attitudes of obstetricians in Australia, New Zealand and the UK towards prenatally diagnosed trisomy 18 (T18). METHOD Obstetricians were contacted by email and invited to participate in an anonymous electronic survey. RESULTS Survey responses were obtained from 1018/3717 (27%) practicing obstetricians/gynaecologists. Most (60%) had managed a case of T18 in the last 2 years. Eighty-five per cent believed that T18 was a ‘lethal malformation’, although 38% expected at least half of liveborn infants to survive for more than 1 week. Twenty-one per cent indicated that a vegetative existence was the best developmental outcome for surviving children. In a case of antenatally diagnosed T18, 95% of obstetricians would provide a mother with the option of termination. If requested, 99% would provide maternal-focused obstetric care (aimed at maternal wellbeing rather than fetal survival), whereas 80% would provide fetal-oriented obstetric care (to maximise fetal survival). Twenty-eight per cent would never discuss the option of caesarean; 21% would always discuss this option. Management options, attitudes and knowledge of T18 were associated with location, practice type, gender and religion of obstetricians. CONCLUSION There is variability in obstetricians' attitudes towards T18...

‣ Characterization of copine VII, a new member of the copine family, and its exclusion as a candidate in sporadic breast cancers with loss of heterozygosity at 16q24.3

Savino, M.; d'Apolito, M.; Centra, M.; van Beerendonk, H.; Cleton-Jansen, A.M.; Whitmore, S.; Crawford, J.; Callen, D.; Zelante, L.; Savoia, A.
Fonte: ACADEMIC PRESS INC Publicador: ACADEMIC PRESS INC
Tipo: Artigo de Revista Científica
Publicado em //1999 Português
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In a search for candidate tumor suppressor genes within a 650-kb common region of loss of heterozygosity (LOH) at 16q24.3 in breast cancer tissues, a 2.6-kb cDNA, named copine VII (CPNE7), was characterized. The gene is 2654 bp and codes for a 633-residue protein with high homology to the other members of the copine family, such as copine I, copine III, and N-copine. The predicted amino acid sequence contains two copies of a C2 domain in the N-terminus. Since these domains have been found in several membrane-binding proteins involved in different intracellular processes, copine VII was viewed as a potential tumor suppressor gene. Mutation analysis was carried out by single-strand conformation polymorphism analysis of 18 breast tumor tissue samples with ascertained LOH on chromosome 16q24.3. Since only two polymorphisms were identified, no evidence was found to indicate that copine VII is the tumor suppressor gene at 16q24.3 involved in breast cancer.; Maria Savino, Maria d'Apolito, Marta Centra, Hetty M. van Beerendonk, Anne-Marie Cleton-Jansen, Scott A. Whitmore, Joanna Crawford, David F. Callen, Leopoldo Zelante and Anna Savoia; Copyright © 1999 Academic Press

‣ Human Base Excision Repair Creates a Bias Toward −1 Frameshift Mutations*

Lyons, Derek M.; O'Brien, Patrick J.
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
Português
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Frameshift mutations are particularly deleterious to protein function and play a prominent role in carcinogenesis. Most commonly these mutations involve the insertion or omission of a single nucleotide by a DNA polymerase that slips on a damaged or undamaged template. The mismatch DNA repair pathway can repair these nascent polymerase errors. However, overexpression of enzymes of the base excision repair (BER) pathway is known to increase the frequency of frameshift mutations suggesting competition between these pathways. We have examined the fate of DNA containing single nucleotide bulges in human cell extracts and discovered that several deaminated or alkylated nucleotides are efficiently removed by BER. Because single nucleotide bulges are more highly exposed we anticipate that they would be highly susceptible to spontaneous DNA damage. As a model for this, we have shown that chloroacetaldehyde reacts more than 18-fold faster with an A-bulge than with a stable A·T base pair to create alkylated DNA adducts that can be removed by alkyladenine DNA glycosylase. Reconstitution of the BER pathway using purified components establishes that bulged DNA is efficiently processed. Single nucleotide deletion is predicted to repair +1 frameshift events...

‣ Manifestaciones clínicas y variabilidad inmunológica en nueve pacientes con síndrome de DiGeorge

Aglony I,Marlene; Lizama C,Macarena; Méndez R,Cecilia; Navarrete S,Carmen; Garay G,Francisco; Repetto L,Gabriela; Pérez L,Rebeca; Carrión A,Flavio; Talesnik G,Eduardo
Fonte: Sociedad Médica de Santiago Publicador: Sociedad Médica de Santiago
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2004 Português
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DiGeorge syndrome is characterized by developmental defects of the heart, parathyroid glands and thymus. Aim: To describe the clinical variability of DiGeorge syndrome and its relation with immunodeficiency. Patients and methods: A three years retrospective chart review from three hospitals of Santiago, Chile was conducted. We included patients with neonatal diagnosis of DiGeorge syndrome. Clinical and immuno-logic data were collected from their initial evaluation. Results: We found 9 patients with DiGeorge syndrome. All had dysmorphic facies, hypocalcemia and congenital heart disease. Three patients had hypoparathyroidism, 4 had interrupted aortic arch type B, 4 had tetralogy of Fallot and 1 had coarctation of aorta. Six patients had other malformations and associated diseases. FISH studies, performed in 8 patients, found the 22q11.2 microdeletion in all. Most patients had low CD3, CD4 and CD8 T cell counts, that ranged for CD3 T cells, between 256/mm3 and 3,664/mm³, for CD4 T cells, between 224/mm3 and 2,649/mm3, for CD8 T cells, between 26/mm³ and 942/mm³. Three patients had CD4 T cells counts <400/mm3 and one had a phytohemagglutinin stimulation index <10. Airway malformations and primary hypoparathyroidism were present in 3 out of 4 patients that died before 18 months compared with the surviving patients (p=0.048). Conclusions: We found variable clinical manifestations as well as CD3...