RESUMO
Implementation of wildfire- and climate-adaptation strategies in seasonally dry forests of western North America is impeded by numerous constraints and uncertainties. After more than a century of resource and land use change, some question the need for proactive management, particularly given novel social, ecological, and climatic conditions. To address this question, we first provide a framework for assessing changes in landscape conditions and fire regimes. Using this framework, we then evaluate evidence of change in contemporary conditions relative to those maintained by active fire regimes, i.e., those uninterrupted by a century or more of human-induced fire exclusion. The cumulative results of more than a century of research document a persistent and substantial fire deficit and widespread alterations to ecological structures and functions. These changes are not necessarily apparent at all spatial scales or in all dimensions of fire regimes and forest and nonforest conditions. Nonetheless, loss of the once abundant influence of low- and moderate-severity fires suggests that even the least fire-prone ecosystems may be affected by alteration of the surrounding landscape and, consequently, ecosystem functions. Vegetation spatial patterns in fire-excluded forested landscapes no longer reflect the heterogeneity maintained by interacting fires of active fire regimes. Live and dead vegetation (surface and canopy fuels) is generally more abundant and continuous than before European colonization. As a result, current conditions are more vulnerable to the direct and indirect effects of seasonal and episodic increases in drought and fire, especially under a rapidly warming climate. Long-term fire exclusion and contemporaneous social-ecological influences continue to extensively modify seasonally dry forested landscapes. Management that realigns or adapts fire-excluded conditions to seasonal and episodic increases in drought and fire can moderate ecosystem transitions as forests and human communities adapt to changing climatic and disturbance regimes. As adaptation strategies are developed, evaluated, and implemented, objective scientific evaluation of ongoing research and monitoring can aid differentiation of warranted and unwarranted uncertainties.
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Incêndios , Incêndios Florestais , Ecossistema , Florestas , Humanos , América do NorteRESUMO
PURPOSE: Carney complex (CNC) is a rare autosomal dominant syndrome, characterized by mucocutaneous pigmentation, cardiac, cutaneous myxomas and endocrine overactivity. It is generally caused by inactivating mutations in the PRKAR1A (protein kinase cAMP-dependent type I regulatory subunit alpha) gene. Acromegaly is an infrequent manifestation of CNC, reportedly diagnosed in 10% of patients. METHODS: We here report the case of a patient who was concomitantly diagnosed with Carney complex, due to a new mutation in PRKAR1A ((NM_002734.3:c.80_83del, p.(Ile27Lysfs*101 in exon 2), and acromegaly. In parallel, we conducted an extensive review of published case reports of acromegaly in the setting of CNC. RESULTS: The 43-year-old patient was diagnosed with an acromegaly due to a GH-secreting pituitary microadenoma resistant to somatostatin analogs. He underwent transsphenoidal surgery in our tertiary referral center, which found a pure GH-secreting adenoma. In the literature, we identified 57 cases (24 men, 33 women) of acromegaly in CNC patients. The median age at diagnosis was 28.8 ± 12 year and there were 6 cases of gigantism. Acromegaly revealed CNC in only 4 patients. 24 patients had a microadenoma and two carried pituitary hyperplasia and/or multiple adenomas, suggesting that CNC may result in a higher proportion of microadenoma as compared to non-CNC acromegaly. CONCLUSIONS: Although it rarely reveals CNC, acromegaly is diagnosed at a younger age in this setting, with a higher proportion of microadenomas.
Assuntos
Acromegalia/diagnóstico , Complexo de Carney/diagnóstico , Acromegalia/genética , Adolescente , Adulto , Complexo de Carney/genética , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Feminino , Humanos , Masculino , Mutação , Adulto JovemRESUMO
BACKGROUND: Epigenetic alterations may represent new therapeutic targets and/or biomarkers of allergic rhinitis (AR). Our aim was to examine genome-wide epigenetic changes induced by controlled pollen exposure in the environmental exposure unit (EEU). METHODS: 38 AR sufferers and eight nonallergic controls were exposed to grass pollen for 3 hours on two consecutive days. We interrogated DNA methylation at baseline and 3 hours in peripheral blood mononuclear cells (PBMCs) using the Infinium Methylation 450K array. We corrected for demographics, cell composition, and multiple testing (Benjamini-Hochberg) and verified hits using bisulfite PCR pyrosequencing and qPCR. To extend these findings to a clinically relevant tissue, we investigated DNA methylation and gene expression of mucin 4 (MUC4), in nasal brushings from a separate validation cohort exposed to birch pollen. RESULTS: In PBMCs of allergic rhinitis participants, 42 sites showed significant DNA methylation changes of 2% or greater. DNA methylation changes in tryptase gamma 1 (TPSG1), schlafen 12 (SLFN12), and MUC4 in response to exposure were validated by pyrosequencing. SLFN12 DNA methylation significantly correlated with symptoms (P < 0.05), and baseline DNA methylation pattern was found to be predictive of symptom severity upon grass allergen exposure (P = 0.029). Changes in MUC4 DNA methylation in nasal brushings in the validation cohort correlated with drop in peak nasal inspiratory flow (Spearman's r = 0.314, P = 0.034), and MUC4 gene expression was significantly increased (P < 0.0001). CONCLUSION: This study revealed novel and rapid epigenetic changes upon exposure in a controlled allergen challenge facility, and identified baseline epigenetic status as a predictor of symptom severity.
Assuntos
Biomarcadores , Exposição Ambiental , Epigenômica , Mucosa Nasal/metabolismo , Rinite Alérgica/etiologia , Rinite Alérgica/metabolismo , Adolescente , Adulto , Idoso , Proteínas de Transporte , Ilhas de CpG , Metilação de DNA , Suscetibilidade a Doenças , Exposição Ambiental/efeitos adversos , Epigênese Genética , Feminino , Perfilação da Expressão Gênica , Humanos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Mucina-4/genética , Pólen/imunologia , Rinite Alérgica/diagnóstico , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/metabolismo , Avaliação de Sintomas , Adulto JovemRESUMO
This article summarises and contextualises the debates which occurred during the Carbon Dioxide Utilisation Faraday Discussion meeting. The utilisation of carbon dioxide is discussed in terms of both conversion to fuel, with a potential impact on atmospheric carbon dioxide levels, and conversion to chemicals with a potential impact on sustainability.
RESUMO
A recessive mutation in the tub gene causes obesity, deafness and retinal degeneration in tubby mice. The tub gene is a member of a family of tubby-like genes (TULPs) that encode proteins of unknown function. Members of this family have been identified in plants, vertebrates and invertebrates. The TULP proteins share a conserved carboxy-terminal region of approximately 200 amino-acid residues. Here we report the analysis of the human gene TULP1, which is expressed specifically in the retina. Upon analysing 162 patients with nonsyndromic recessive retinitis pigmentosa (RP) and 374 simplex cases of RP, we found two who were compound heterozygotes for mutations that cosegregated with disease in the respective families. Three of the mutations are missense changes affecting the conserved C-terminal region; the fourth mutation affects a splice donor site upstream of this region. Our data suggest that mutations in TULP1 are a rare cause of recessive RP and indicate that TULP1 has an essential role in the physiology of photoreceptors.
Assuntos
Proteínas do Olho/genética , Genes Recessivos , Mutação Puntual , Retinose Pigmentar/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Humanos Par 6 , Proteínas do Olho/química , Feminino , Triagem de Portadores Genéticos , Humanos , Masculino , Camundongos , Núcleo Familiar , LinhagemRESUMO
BACKGROUND: Videofluoroscopy (VFSS) is a dynamic fluoroscopic examination of swallowing function to assess oropharyngeal dysphagia. In the United Kingdom (UK), this test is typically performed by a team of Speech and Language Therapists (SLTs), radiologists and radiographers. While VFSS is undertaken across the UK, recent literature reflects wide variation in the procedure itself. OBJECTIVES: The role of the advanced practitioner gastrointestinal (GI) radiographer within a VFSS service will be illustrated by the narrative description of a VFSS service in a large NHS teaching hospital in England. The paper compares the existing VFSS service against recent literature outlining national practice, with particular focus upon the growing role of the advanced practitioner GI radiographer. Existing pressures upon the National Health Service (NHS) are examined as contributing factors. Lastly, further plans to improve the clinic are delineated. KEY FINDINGS: Recent literature shows a wide national variation in the running of VFSS services. Pertinently, the evidence suggests that radiologists are becoming progressively less involved in these clinics, with a move towards more practitioner-led services. The changes to the described VFSS service are in line with national trends, and the described clinic is an effective example of a practitioner-led service which fully utilises the role of the advanced practitioner GI radiographer. CONCLUSION: This paper demonstrates that a practitioner-led service can benefit both patients and staff. Further improvement work is ongoing, with a particular need to involve service users and collect more meaningful outcome measures. IMPLICATIONS FOR PRACTICE: The growing move towards practitioner-led clinics is likely to continue. However, the wide variation in practice nationally and lack of consistent, recognised training that meets the needs of both SLT and radiographers, needs to be addressed.
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Terapia da Linguagem , Fala , Humanos , Terapia da Linguagem/métodos , Medicina Estatal , Fonoterapia/métodos , Reino UnidoRESUMO
The past year has seen substantial progress in our understanding the molecular mechanisms of bodyweight regulation, particularly in the central and peripheral actions of the leptin and melanocortin signaling pathways (e.g. leptin stimulation of angiogenesis and suppression of cytokine production). Important advances also include the identification of mutations in components of the leptin and melanocortin pathways in human obese families. Expanding from the positional cloning of leptin some five years ago, the mouse continues to be a central focus of study, particularly the way in which different bodyweight-sensing pathways interact in different feeding states.
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Obesidade/genética , Animais , Regulação da Temperatura Corporal , Humanos , Hipotálamo/fisiopatologia , Leptina/fisiologia , Obesidade/fisiopatologiaRESUMO
Despite the influence of obesity in predisposing to many diseases, and evidence for high heritability, efforts to identify human genes with major effects on bodyweight have not yet been successful. In contrast, remarkable progress has been made in the identification and characterization of the genes mutated in five monogenic mouse models of obesity. These genes have led to new insights into the etiology of obesity and provide promising targets for therapeutic intervention.
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Camundongos Endogâmicos/genética , Camundongos Obesos/genética , Obesidade/genética , Animais , Modelos Animais de Doenças , Humanos , CamundongosRESUMO
Control and quercetin dihydrate-supplemented (2â¯g/kg) feeds were fed to 32 New Zealand White rabbits (both sexes) from 5 to 12â¯weeks old. Slaughter weight, carcass and organ weights, meat yields and physical and proximate meat quality were determined. Quercetin increased the hindleg meat:bone ratio (Pâ¯<â¯.001) by reducing hindleg bone weight (Pâ¯=â¯.01), contrary to the current understanding of the effect of quercetin on the skeletal system. However, this and the increase in skin weight (Pâ¯=â¯.03) may have been due to the effects of quercetin on connective tissue. Sex affected spleen weight (Pâ¯=â¯.04; female > male), head weight (Pâ¯<â¯.001; male > female), reference carcass yield (Pâ¯=â¯.02, female > male) and loin pHu (Pâ¯=â¯.02; male > female), without commercial implications. Other physical and chemical meat quality traits were not affected by diet or sex.
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Fenômenos Fisiológicos da Nutrição Animal , Composição Corporal/efeitos dos fármacos , Suplementos Nutricionais , Carne/análise , Quercetina/farmacologia , Ração Animal , Animais , Osso e Ossos , Tecido Conjuntivo , Dieta , Feminino , Membro Posterior , Humanos , Masculino , Músculos , Nova Zelândia , Tamanho do Órgão , Coelhos , Pele , Especificidade da Espécie , BaçoAssuntos
Antígenos de Neoplasias/genética , Moléculas de Adesão Celular/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Deleção de Sequência , Adulto , Idoso , Idoso de 80 Anos ou mais , Reparo de Erro de Pareamento de DNA/genética , Molécula de Adesão da Célula Epitelial , Éxons , Feminino , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Mutação , Fatores de RiscoRESUMO
Structural requirements of 5S rRNA for nuclear transport and RNA-protein interactions have been studied by analyzing the behavior of oocyte-type 5S rRNA and of 31 different in vitro-generated mutant transcripts after microinjection into the cytoplasm of Xenopus oocytes. Experiments reveal that the sequence and secondary and/or tertiary structure requirements of 5S rRNA for nuclear transport, storage in the cytoplasm as 7S ribonucleoprotein particles, and assembly into 60S ribosomal subunits are complex and nonidentical. Elements of loops A, C, and E, helices II and V, and bulged and hinge nucleotides in the central domain of 5S rRNA carry the essential information for these functional activities. Assembly of microinjected 5S rRNA into 60S ribosomal subunits was shown to occur in the nucleus; thus, the first requirement for subunit assembly is nuclear targeting. The inhibitory effects of ATP depletion, wheat germ agglutinin, and chilling on the nuclear import of 5S rRNA indicate that it crosses the nuclear envelope through the nuclear pore complex by a pathway similar to that used by karyophilic proteins.
Assuntos
Núcleo Celular/metabolismo , Oócitos/metabolismo , RNA Ribossômico 5S/metabolismo , Ribonucleoproteínas/biossíntese , Ribossomos/metabolismo , Animais , Composição de Bases , Sequência de Bases , Sítios de Ligação , Feminino , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Conformação de Ácido Nucleico , Ovário , RNA Ribossômico 5S/biossíntese , RNA Ribossômico 5S/química , Fator de Transcrição TFIIIA , Fatores de Transcrição/análise , Fatores de Transcrição/metabolismo , Transcrição Gênica , Xenopus laevisRESUMO
The Nucleolar Localization Elements (NoLEs) of Xenopus laevis U3 small nucleolar RNA (snoRNA) have been defined. Fluorescein-labeled wild-type U3 snoRNA injected into Xenopus oocyte nuclei localized specifically to nucleoli as shown by fluorescence microscopy. Injection of mutated U3 snoRNA revealed that the 5' region containing Boxes A and A', known to be important for rRNA processing, is not essential for nucleolar localization. Nucleolar localization of U3 snoRNA was independent of the presence and nature of the 5' cap and the terminal stem. In contrast, Boxes C and D, common to the Box C/D snoRNA family, are critical elements for U3 localization. Mutation of the hinge region, Box B, or Box C' led to reduced U3 nucleolar localization. Results of competition experiments suggested that Boxes C and D act in a cooperative manner. It is proposed that Box B facilitates U3 snoRNA nucleolar localization by the primary NoLEs (Boxes C and D), with the hinge region of U3 subsequently base pairing to the external transcribed spacer of pre-rRNA, thus positioning U3 snoRNA for its roles in rRNA processing.
Assuntos
Nucléolo Celular/fisiologia , RNA Nuclear Pequeno/química , RNA Nuclear Pequeno/genética , Animais , Sequência de Bases , Nucléolo Celular/ultraestrutura , Primers do DNA , Feminino , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Conformação de Ácido Nucleico , Oócitos/fisiologia , Reação em Cadeia da Polimerase , RNA Nuclear Pequeno/biossíntese , Transcrição Gênica , Xenopus laevisRESUMO
GOALS: 1) analyse the knowledge, attitudes and practices of Lome population about blood donation; 2) identify obstacles to blood donation among the population of Lome; 3) suggest some solutions to improve the performance of the National Blood Transfusion Centre (CNTS). METHODOLOGY: We have conducted a sample survey among the population of Lome from the 6th to 21st October 2003. Three hundred persons filled a questionnaire. RESULTS: In the sample, 183 (61%) were males. Their age ranged from 18 to 67 years with 2/3 of young peoples between 18 and 37 years. Pupils/students were 24,33%, wage-earners, 55% and the unemployed, 17,67%. More than the half of the investigated persons (54,67%) were unmarried and 96, 33% persons were literate. Nearly all the people (96,33%) knew about blood donation in Lome and they have received information mainly from friends, media and sensitization by the CNTS. Sixty-one percent of the investigated knew where blood is donated. All the investigated were unanimous about the vital role of blood. Whatever their religion, they recognized its sacred nature. The majority of the investigated (85%) were willing to donate blood. Only 95 people were donors. The reasons for non-donation were mainly related to the fear of catching diseases (31,71%) especially the HIV (9,76%), the lack of information (25,37%), the religious beliefs (19,51%) and the fear of knowing the result of one's HIV test. 277 people (92,33%) said that blood should be donated without remuneration. CONCLUSION: There is a growing interest in the blood donation among the population of Lome but new strategies must be elaborated to inform the population and motivate blood donors.
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Doadores de Sangue , Transfusão de Sangue , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Idoso , Coleta de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , TogoRESUMO
This study describes the changes taking place during rigour in springbok (Antidorcas marsupialis) Longissimus thoracis et lumborum (LTL) and Biceps femoris (BF) muscles. Samples from six male and six female springbok were snap-frozen at 2, 3, 5, 8, 12, 18, 24 and 30h post-mortem (PM) and the pH, calpains I, II and calpastatin activities and cathepsins B, BL and H activities were determined. The temperature was also recorded. Significant third-order interactions were found for the pH and temperature, with the female LTL cooling more rapidly and acidifying slower than the other samples. Female muscles were at risk of developing cold-shortening and all the samples cooled more rapidly than recommended for cattle or sheep. Cathepsin BL activity increased PM, likely due to the degradation of the lysosomes. Calpains I, II and calpastatin activity declined during rigour, indicating that the calpains were activated early PM. Gender and muscle had a significant effect on calpain and cathepsin activity.
Assuntos
Antílopes/fisiologia , Qualidade dos Alimentos , Armazenamento de Alimentos , Carne/análise , Músculo Esquelético/química , Rigor Mortis/veterinária , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Calpaína/antagonistas & inibidores , Calpaína/metabolismo , Catepsinas/metabolismo , Fenômenos Químicos , Feminino , Concentração de Íons de Hidrogênio , Isoenzimas/metabolismo , Masculino , Fenômenos Mecânicos , Músculo Esquelético/enzimologia , Músculo Esquelético/metabolismo , Proteólise , Refrigeração , Rigor Mortis/enzimologia , Rigor Mortis/metabolismo , Caracteres Sexuais , África do Sul , Estresse Fisiológico , Estresse Psicológico/enzimologia , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologiaRESUMO
The effect of lowering the incubation temperature of sucrose-grown cultures of Neurospora crassa on the level of various enzyme activities was investigated. Of twelve inducible/derepressible activities studied, three, in addition to glycerol kinase, were found to increase during 48 h of incubation at 4-6 degrees C: trehalase (increase in specific activity of 3-10-fold), beta-glucosidase (6-12-fold) and beta-N-acetylglucosaminidase (4 to 6-fold). The maximum increases occurred at 6 degrees C and no increases took place in mycelia incubated at 0 degrees C. The kinetics of the changes in activity were markedly different from those observed previously with glycerol kinase. The increases were inhibited by cycloheximide. Trehalase, beta-glucosidase and beta-N-acetylglucosaminidase activities were not rapidly lost when cultures incubated at 6 degrees C were returned to 26 degrees C.
Assuntos
Acetilglucosaminidase/metabolismo , Glucosidases/metabolismo , Hexosaminidases/metabolismo , Neurospora crassa/enzimologia , Neurospora/enzimologia , Trealase/metabolismo , Divisão Celular , Cicloeximida/farmacologia , Glicerol Quinase/metabolismo , Cinética , Neurospora crassa/efeitos dos fármacos , Temperatura , Fatores de TempoRESUMO
The level of glycerol kinase activity in Neurospora crassa was shown to change in response to resuspension of sucrose-grown mycelia in fresh medium containing a new carbon source: the magnitude of the change depended on the new carbon source provided. Certain carbon sources, such as glucose and fructose, inhibited the small increase that occurred in the absence of any carbon source. Others, and in particular deoxyribose, galactose, glycerol and ribose, greatly enhanced this increase. The activity induced by deoxyribose and galactose had the same stability, both in vivo and in vitro, as that induced by glycerol, and as that induced by incubation of Neurospora cultures at low temperatures. The inhibitory carbon sources, such as glucose and fructose, also restricted the increases induced by deoxyribose, galactose and glycerol: they had more effect on the increases induced by glycerol and deoxyribose than on that induced by galactose. The increase in activity that occurs at low temperature was also inhibited by glucose and sucrose.
Assuntos
Carboidratos/farmacologia , Glicerol Quinase/metabolismo , Neurospora crassa/enzimologia , Neurospora/enzimologia , Fosfotransferases/metabolismo , Metabolismo dos Carboidratos , Cinética , Neurospora crassa/efeitos dos fármacos , Neurospora crassa/metabolismo , Desnaturação Proteica , Sacarose/farmacologia , TemperaturaRESUMO
Proteinase activity in the cellular slime mould Dictyostelium discoideum has been analyzed by electrophoresis on polyacrylamide gels containing denatured hemoglobin. At least eight bands due to acid proteinases have been defined using extracts of myxamoebae, four bands A-D which move faster than the fifth and major band E, a minor band E' which moves just behind E and two slow bands G and H. Fruiting body formation was accompanied by the appearance of one new proteinase band F. The proteinases were present in extracts of both axenically-grown and bacterially-grown cells. Differences between the pH dependence and stability of the individual proteinases were detected. Inhibitor studies suggested that the faster proteinases A-D may be cathepsin B-like, whilst the slower enzymes E, E' and F do not fit readily into any known group of proteinases since they were sensitive to HgCl2 but not to other inhibitors of cathepsin B and not to inhibitors of cathepsin D-like proteinases under standard conditions. None of the proteinases was apparently formed during or after preparation of extracts and the proteinases could be re-run on polyacrylamide gels to give only the band expected from the first run. The bands are believed to reflect multiple proteinase activities within the cell.
Assuntos
Dictyostelium/enzimologia , Peptídeo Hidrolases/metabolismo , Eletroforese em Gel de Poliacrilamida , Concentração de Íons de Hidrogênio , Peptídeo Hidrolases/isolamento & purificação , Inibidores de Proteases/farmacologiaRESUMO
The sulfonylurea receptor (SUR) is a key component in glucose-stimulated insulin secretion. Obesity and NIDDM are frequently associated and share some metabolic abnormalities, suggesting that they might also share some susceptibility genes. Thus, the SUR encoding gene is a plausible candidate for a primary pancreatic beta-cell defect and thus for hyperglycemia and weight gain. Through association and linkage studies, we have investigated the potential role of the SUR gene in families with NIDDM and in two independent sets of morbidly obese families. The exon 22 T-allele at codon 761 was more common in patients with NIDDM (7.7%) and morbid obesity (7.8%) than in control subjects (1.8%, P = 0.030 and P = 0.023, respectively). This variant was associated with morbid obesity (odds ratio 3.71, P = 0.017) and NIDDM (odds ratio 2.20, P = 0.04; association dependent on BMI). Although the frequencies for intron 24 variant were similar in all groups, morbidly obese patients homozygous for the c-allele had a more deleterious form of obesity. Sib-pair linkage studies with NIDDM in French Caucasian families gave no evidence for linkage to the SUR locus. However, in one set of the obese families, we found an indication for linkage with a SUR-linked microsatellite marker (D11S419, P = 0.0032). We conclude that in Caucasians, the SUR locus may contribute to the genetic susceptibility to NIDDM and obesity.
Assuntos
Transportadores de Cassetes de Ligação de ATP , Cromossomos Humanos Par 11/genética , Diabetes Mellitus Tipo 2/genética , Obesidade Mórbida/genética , Canais de Potássio Corretores do Fluxo de Internalização , Canais de Potássio/genética , Receptores de Droga/genética , População Branca/genética , Adulto , Mapeamento Cromossômico , Estudos de Coortes , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , França/epidemiologia , Frequência do Gene , Genótipo , Humanos , Modelos Logísticos , Masculino , Obesidade Mórbida/etnologia , Obesidade Mórbida/fisiopatologia , Receptores de SulfonilureiasRESUMO
Obesity is one of the most significant risk factors for hypertension, coronary heart disease, and NIDDM (Frayn KN, Coppack SW: Insulin resistance, adipose tissue and coronary heart disease. Clin Sci 82:1-8, 1992; Kaplan NM: The deadly quartet: upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med 149:1514-1520, 1989). While family segregation, adoption, and twin studies have indicated that degree of adiposity has a significant genetic component (Stunkard AJ, Harris JR, Pedersen NL, McClearn GE: The body-mass index of twins who have been reared apart. N Engl J Med 322:1483-1487, 1990; Bouchard C, Despres J-P, Mauriege P: Genetic and nongenetic determinants of regional fat distribution. Endocr Rev 14:72-93, 1993), the genes and predisposing mutations remain poorly understood. This is in contrast to several well-defined genetic models for obesity in rodents, particularly the mouse obese (ob) gene, in which loss-of-function mutations cause severe obesity. Recent studies have demonstrated a substantial reduction in body fat when recombinant ob protein (leptin) is administered to mice. To test the relevance of these observations to human obesity, the location of the human homologue (OB) was established by radiation hybrid mapping and eight microsatellite markers spanning the OB gene region (7q3l.3) were genotyped in 101 obese French families. Affected-sib-pair analyses for extreme obesity, defined by BMI >35 kg/m2, revealed suggestive evidence for linkage to three markers located within 2 cM of the OB gene (D7S514, D7S680, and D7S530). The OB gene is therefore a candidate for genetic predisposition to extreme obesity in a subset of these families.
Assuntos
Cromossomos Humanos Par 7 , Obesidade Mórbida/genética , Proteínas/genética , Alelos , Animais , Sequência de Bases , Índice de Massa Corporal , Mapeamento Cromossômico , Primers do DNA , Família , Ligação Genética , Marcadores Genéticos , Genótipo , Humanos , Leptina , Desequilíbrio de Ligação , Camundongos , Dados de Sequência Molecular , Núcleo Familiar , Reação em Cadeia da Polimerase , RoedoresRESUMO
To identify genes that influence plasma cholesterol, triglyceride, and high-density and low-density lipoproteins concentrations we conducted a genome-wide scan using 354 polymorphic markers spaced at 10-cM intervals in 75 obese but otherwise normal human families. The results of the genome scan using sibling pair analysis of quantitative phenotypes suggested that 1q21-q23 contains a locus that influences plasma cholesterol concentration. Chromosome 12 gave evidence of linkage to plasma triglyceride concentration (D12SPAH) and chromosomes 3, 6, 7, 10, 11, 17, and 20 yielded additional evidence of linkage for lipid phenotypes at lower levels of statistical significance. Allele sharing for markers near prominent candidate genes was either very weakly related or unrelated to sibling similarity for lipid concentrations. Together these results suggest that genes with important roles in regulating normal cholesterol and triglyceride concentrations do not coincide with the location of previously known candidate genes.