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Various Genotypes (various + genotype)
Selected AbstractsEvaluation and application of reverse transcription loop-mediated isothermal amplification for detection of noroviruses,JOURNAL OF MEDICAL VIROLOGY, Issue 3 2007Tomoko Yoda Abstract A one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of norovirus (NV) was developed. In order to design primer sets for the detection of a wide range of NVs, NVs were categorized into three groups, that is, genogroup I (GI), prevalent GII, and minor GII; three sets of primers were developed for each group. Clinical specimens of patients suffering from enteric RNA viruses, such as NV, group A and C rotavirus, and sapovirus were examined using these primer sets. Various genotypes of NVs were detected in clinical specimens from patients infected with NV where no false positive reaction was observed with other enteric RNA viruses. Additionally, 88 samples of acute gastroenteritis outbreaks were analyzed by an RT-LAMP assay and compared with the results of routine RT-PCR. The results of the RT-LAMP assay corresponded well to that of RT-PCR. These findings suggest the practical application of the RT-LAMP assay for the detection of NVs in clinical specimens. Consequently, the RT-LAMP system and conventional detection kits (NVGI and NVGII detection kits; Eiken Chemical Co., Ltd., Japan) were compared. The detection rate of the prevalent and minor GII primer sets was similar to that of the conventional NVGII kit, while the detection rate of the GI primer set is different because it can detect several genotypes better than the conventional NVGI kit. This is an initial report that the RT-LAMP system is able to detect NVs in clinical specimens within a wide range. J. Med. Virol. 79:326,334, 2007. © 2007 Wiley-Liss, Inc. [source] Geographical differences within Finland in the frequency of HLA-DQ genotypes associated with Type 1 diabetes susceptibilityINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4 2000J. Ilonen Geographical variations in the HLA-DQ genotypes associated with risk for type 1 diabetes were evaluated in Finland. Samples of 280 diabetic children diagnosed in Turku (south-west of the country) and 405 in Oulu (north of the country) were studied as well as a series of 14 096 and 10 016 newborns collected from the same hospitals. There were no major differences in the risk or protection conferred by various HLA-DQB1 genotypes between south-western and northern parts of the country when genotypes of children with type 1 diabetes from these two centres were compared with those of newborns, representing the background populations. However, the distribution of various genotypes was different, both in diabetic children and in newborns, when compared between the two regions (P < 0.0001, ,2 test). These differences reflected the allele frequencies in newborn cohorts in which HLA-DQB1*02 and DQB1*0301 were found more often in Turku and DQB1*0302 more often in Oulu (P < 0.0001 for all differences). Similar types of differences were detected when children who were diagnosed as having diabetes during the national ,Childhood Diabetes in Finland' (DiMe) study between the years 1986,1989 were compared according to their residence. The observed differences in genotype and allele frequencies demonstrate the heterogeneity for HLA alleles even in a population that is generally regarded as highly homogeneous. These differences also affect the sensitivity and efficiency of the screening programme used for identifying infants with genetic susceptibility to IDDM in the ongoing Finnish Diabetes Prediction and Prevention Study. [source] Genetic and Other Contributions to Alcohol Intake in Rhesus Macaques (Macaca mulatta)ALCOHOLISM, Issue 3 2006Joseph G. Lorenz Background: The etiology of alcoholism and alcohol abuse, like many other complex diseases, is heterogeneous and multifactorial. Numerous studies demonstrate a genetic contribution to variation in the expression of alcohol-related disorders in humans. Over the past decade, nonhuman primates have emerged as a valuable model for some aspects of human alcohol abuse because of their phylogenetic proximity to humans. Long-term, longitudinal studies of rhesus macaques (Macaca mulatta) have provided much insight into environmental influences, especially early life experiences, on alcohol consumption and behavior patterns that characterize alcohol intake later in life. It is not known, however, whether there is a genetic component as well to the variation seen in alcohol consumption in rhesus macaques. A significant genetic component to variation in alcohol consumption in rhesus macaques would show for the first time that like humans, for nonhuman primates additive genetic influences are important. Moreover, their use as a model for alcohol-related disorders in humans would have even greater relevance and utility for designing experiments incorporating the expanding molecular genetics field, and allow researchers to investigate the interaction among the known environmental influences and various genotypes. Methods: In this study, we investigate factors contributing to variation in alcohol consumption of 156 rhesus macaques collected over 10 years when subjects were adolescent in age, belonging to a single extended pedigree, with each cohort receiving identical early rearing backgrounds and subsequent treatments. To measure alcohol consumption each animal was provided unfettered simultaneous access both to an aspartame-sweetened 8.4% (v/v) alcohol-water solution, the aspartame-sweetened vehicle, and to water for 1 hour each day during the early afternoon between 13:00 and 15:00 in their home cages for a period of 5 to 7 weeks. We use multiple regression to identify factors that significantly affect alcohol consumption among these animals and a maximum likelihood program (ASReml) that, controlling for the significant factors, estimates the genetic contribution to the variance in alcohol consumption. Results: Multiple regression analysis identified test cohort and rearing environment as contributing to 57 and 2%, respectively, of the total variance in alcohol consumption. Of the remaining 41% of the variance about half (19.8%) was attributable to additive genetic effects using a maximum likelihood program. Conclusion: This study demonstrates that, as in humans, there are additive genetic factors that contribute to variation in alcohol consumption in rhesus macaques, with other nongenetic factors accounting for substantial portions of the variance in alcohol consumption, Our findings show the presence of an additive genetic component and suggest the potential utility of the nonhuman primate as a molecular genetics tool for understanding alcohol abuse and alcoholism. [source] MRI monitoring of focal cerebral ischemia in peroxisome proliferator-activated receptor (PPAR)-deficient miceNMR IN BIOMEDICINE, Issue 3 2007Jean-Baptiste Pialat Abstract Peroxisome proliferator-activated receptors (PPARs) are a potential target for neuroprotection in focal ischemic stroke. These nuclear receptors have major effects in lipid metabolism, but they are also involved in inflammatory processes. Three PPAR isotypes have been identified: ,, , (or ,) and ,. The development of PPAR transgenic mice offers a promising tool for prospective therapeutic studies. This study used MRI to assess the role of PPAR, and PPAR, in the development of stroke. Permanent middle cerebral artery occlusion induced focal ischemia in wild-type, PPAR, -null mice and PPAR, -null mice. T2 -weighted MRI was performed with a 7 T MRI scan on day 0, 1, 3, 7 and 14 to monitor lesion growth in the various genotypes. General Linear Model statistical analysis found a significant difference in lesion volume between wild-type and PPAR-null mice for both , and , isotypes. These data validate high-resolution MRI for monitoring cerebral ischemic lesions, and confirm the neuroprotective role of PPAR, and PPAR, in the brain. Copyright © 2007 John Wiley & Sons, Ltd. [source] The influence of CYP2B6, CYP2C9 and CYP2D6 genotypes on the formation of the potent antioestrogen Z-4-hydroxy-tamoxifen in human liverBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2002Janet K. Coller Aims, To investigate in a large panel of 50 human liver samples the contribution of CYP2C9, CYP2D6, and CYP3A4 to the overall formation of the potent antioestrogen Z-4-hydroxy-tamoxifen, and how various genotypes affect its formation from tamoxifen. Methods, The formation of Z-4-hydroxy-tamoxifen from 10 µm tamoxifen was studied in human liver microsomes (n=50), characterized for CYP2B6, CYP2C9, CYP2D6 and CYP3A4 expression, and CYP2B6, CYP2C9 and CYP2D6 genotype. The effect of chemical and monoclonal antibody inhibitors, and the formation in supersomes expressing recombinant CYP isoforms was also investigated. Z-4-hydroxy-tamoxifen was quantified using LC-MS analysis. Results, Z-4-hydroxy-tamoxifen was formed by supersomes expressing CYP2B6, CYP2C9, CYP2C19 and CYP2D6, but not CYP3A4. In agreement with these data, the mean formation of Z-4-hydroxy-tamoxifen was inhibited 49% by sulphaphenazole (P=0.001), 38% by quinidine (P<0.05) and 13% by monoclonal antibody against CYP2B6 (MAB-2B6, P<0.05). Furthermore, Z-4-hydroxy-tamoxifen formation significantly correlated with both CYP2C9 expression (rs=0.256, P<0.05) and CYP2D6 expression (rs=0.309, P<0.05). Genotypes of CYP2D6, CYP2B6 and CYP2C9 had an effect on metabolite formation in such a way that samples with two nonfunctional CYP2D6, or two variant CYP2C9 or CYP2B6 alleles, showed lower enzyme activity compared with those with two functional or wild-type alleles, (5.0 vs 9.9 pmol mg,1 protein min,1, P=0.046, 5.1 vs 9.9 pmol mg,1 protein min,1, P=0.053, and 6.8 vs 9.4 pmol mg,1 protein min,1, P=0.054, respectively). CYP2D6 and CYP2C9 contribute on average 45 and 46%, respectively, to the overall formation of Z-4-hydroxy-tamoxifen. Conclusions,CYP2B6, CYP2C9 and CYP2D6 genotypes all affected Z-4-hydroxy-tamoxifen formation and can predict individual ability to catalyse this reaction. [source] Aiming towards effective preventive medicine against Japanese cedar pollinosis: epidemiology, patient investigation and integrated research including genotype analysesCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 2 2005N. Terada Summary Environmental rather than genetic factors appear to play the major role in the recent increased prevalence of Japanese cedar pollinosis in Japan. However, investigating the genes that determine IgE levels and analysing gene polymorphisms may assist in finding new methods of treatment and establishing preventive medicine against this disease. Among a total of 219 asymptomatic individuals who were anti-Japanese cedar pollen IgE antibody positive as determined by radioallergosorbent test (RAST), only a handful subsequently developed symptoms of Japanese cedar pollinosis or secondary onset of Japanese cedar pollinosis over 5,14 years of follow-up. Among those who subsequently developed secondary onset of disease, >50% were found to have high initial RAST scores, suggesting that the incidence of Japanese cedar pollinosis is correlated with RAST score. Hence, it may be prudent to advise asymptomatic individuals with high RAST scores to avoid exposure to Japanese cedar pollen so as to delay onset of the disease. Analysis of sequence variants of the Fc,RI, gene revealed that patients with nasal allergy exhibit a single-nucleotide polymorphism in which the amino acid at 237 of the intracellular domain changes from glutamine to glycine more frequently than individuals without nasal allergy. Furthermore, Il homo polymorphism of the IL-4R, gene is associated with higher serum nonspecific IgE and Japanese cedar pollen-specific IgE levels than are seen in individuals showing Il,Val hetero and Val homo expression types. When the age of pollinosis onset was compared among these three genotypes, it was found to be significantly lower among Il homo type than the other two expression types, suggesting that Il homo type individuals seem characteristically pre-disposed to early onset of pollinosis. Studies comparing eosinophil-associated gene polymorphism in healthy and pollinosis phenotypes have revealed several relationships among the various genotypes and specific disease parameters and suggest that Eotaxin G (123G/A) and IL5 (,703C/T) genotypes can affect the timing of symptom onset after sensitization as well as nasal mucosal hyper-responsiveness. [source] | ||||||||||