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71.
Intraperitoneal infection with Salmonella abortusovis is partially controlled by a gene closely linked with the Ity gene.
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I P Oswald F Lantier R Moutier M F Bertrand E Skamene 《Clinical and experimental immunology》1992,87(3):373-378
The aim of the present study was to determine whether the Ity gene, which controls the resistance to S. typhimurium infection in mice, also governs the resistance to S. abortusovis, a serotype specific for goat and sheep. During either i.v. or i.p. infection, BALB/c mice (Itys) were not able to control the growth of S. abortusovis and eventually died from infection. In contrast CBA (Ityr) or (C.CB)F1 (Ityr/s) mice were able to control the growth of these bacteria. Using congenic C.D2 Ityr mice, we found that the gene controlling resistance to S. abortusovis was tightly linked to the Ity gene on chromosome 1. Furthermore, in the spleen and the liver of backcross BALB/c x (CBA x BALB/c) mice, the S. abortusovis resistance phenotype cosegregated with the two alleles of the Len-1 gene, a gene tightly linked to the Ity gene. By contrast, in these backcross mice, the level of infection of the peritoneal cavity, the site of inoculation, did not correlated with the Len-1 phenotype of the animal. These results provide evidence that after i.p. inoculation the control of S. abortusovis growth in the spleen and the liver is controlled by the Ity gene, but also suggest that additional gene(s) regulate the number of bacteria at the site of inoculation. 相似文献
72.
The apparent concentration-effect relationship is the ensemble of many effector units (such as individual cells or channels)
that do not always exhibit a uniform stimulus-effect relationship. This concept is substantiated by many observations of heterogeneity
in receptor-effector populations including hormone secreting cells, response to hormonal stimuli, activity pattern of second
messengers, stimulus-evoked synaptic currents, and single ion channels. The relationship between drug concentration and magnitude
of pharmacologic response is commonly described by the sigmoidalE
max model which was derived from the Hill equation. The sigmoidicity factor (N) in this model is assumed to be a pure mathematical parameter without physiological connotations. This work demonstrates
that the numerical value ofN (measured empirically) is the product of two factors: (i) the degree of heterogeneity of the effector subunits, i.e., the
elemental component that upon drug stimulus contributes its pharmacological effect independently and does not interact with
other subunits (it could range from a single receptor up to a whole tissue), and (ii) value ofN
*—the shape factor of the subunits' concentration-effect relationship. A special case of this approach occurs whenN
*>5, which is an on-off case. HereN is determined by the distribution (density equation) of the subunit values. In case of heterogeneity of the microparameters
of the effector subunits the apparentN will always have a lower value thanN
*. According to this theory it can be concluded that without knowledge of the distribution of the microparameters no mechanistic
interpretation can be deduced from the apparentN value. If in the futureN
* can be determined by theoretical or experimental methods, the distribution function relatingN
* toN can be calculated. The relevance of this theory is increased in view of the progress being made in advanced research techniques
which may enable us to determine the concentration-effect relationship at the level of the individual effector unit. 相似文献
73.
Numerical comparisons of two formulations of the logistic regressive models with the mixed model in segregation analysis of discrete traits. 总被引:4,自引:0,他引:4
Segregation analysis of discrete traits can be conducted by the classical mixed model and the recently introduced regressive models. The mixed model assumes an underlying liability to the disease, to which a major gene, a multifactorial component, and random environment contribute independently. Affected persons have a liability exceeding a threshold. The regressive logistic models assume that the logarithm of the odds of being affected is a linear function of major genotype effects, the phenotypes of older relatives, and other covariates. A formulation of the regressive models, based on an underlying liability model, has been recently proposed. The regression coefficients on antecedents are expressed in terms of the relevant familial correlations and a one-to-one correspondence with the parameters of the mixed model can thus be established. Computer simulations are conducted to evaluate the fit of the two formulations of the regressive models to the mixed model on nuclear families. The two forms of the class D regressive model provide a good fit to a generated mixed model, in terms of both hypothesis testing and parameter estimation. The simpler class A regressive model, which assumes that the outcomes of children depend solely on the outcomes of parents, is not robust against a sib-sib correlation exceeding that specified by the model, emphasizing testing class A against class D. The studies reported here show that if the true state of nature is that described by the mixed model, then a regressive model will do just as well. Moreover, the regressive models, allowing for more patterns of family dependence, provide a flexible framework to understand gene-environment interactions in complex diseases. 相似文献
74.
Detection of linkage under heterogeneity: comparison of the two-locus vs. admixture models. 总被引:9,自引:0,他引:9
L R Goldin 《Genetic epidemiology》1992,9(1):61-66
Linkage analysis under the two-locus model and the admixture model was compared on pedigree data for a common disease stimulated under a model of genetic heterogeneity. The ascertainment of families was designed so that the samples had a large proportion of families segregating for both disease loci. The two-locus linkage analysis model did not demonstrate increased power of detecting linkage or more accurate estimates of the recombination fraction, theta than did the admixture model linkage analysis. When a sample was purposely chosen so that all of the families were segregating for both loci, then the two-locus lod score analysis was better. However, the increased power depended on assuming the correct gene frequency for the linked locus. It can be concluded that under the conditions of genetic heterogeneity examined here, testing for linkage under the admixture model is the preferred method of analysis. However, this is not a general conclusion that can apply to all two-locus disease models. 相似文献
75.
While the season-of-birth effect is one of the most consistent epidemiological features of schizophrenia, there is a lack
of consistency with respect to the interaction between season of birth and family history of schizophrenia. Apart from family
history, measures related to consanguinity can be used as proxy markers of genomic heterogeneity. Thus, these measures may
provide an alternate, indirect index of genetic susceptibility. We had the opportunity to explore the interaction between
season of birth and measure of consanguinity in well-described genetic isolates in Daghestan, some of which are known for
their relatively high prevalence of schizophrenia. Our previous population-genetic study showed Daghestan has an extremely
high genetic diversity between the ethnic populations and a low genetic diversity within them. The isolates selected for this
study include some with more than 200 and some with less than 100 generations of demographical history since their founding.
Based on pedigrees of multiply-affected families, we found that among individuals with schizophrenia, the measure of consanguinity
was significantly higher in the parents of those born in winter/spring compared to those born in summer/autumn. Furthermore,
compared to summer/autumn born, winter/spring born individuals with schizophrenia had an earlier age-of-onset, and more prominent
auditory hallucinations. Our results suggest that the offspring of consanguineous marriages, and thus those with reduced allelic
heterogeneity, may be more susceptible to the environmental factor(s) underpinning the season-of-the effect in schizophrenia. 相似文献
76.
SNP及其在畜牧业中的应用前景 总被引:4,自引:0,他引:4
张利平 《国外畜牧学(草食家畜)》2003,(3):30-32
SNP(single nucleotide polymorphisns-单核苷酸多态性)是继限制性片段长度多态性和微卫星之后,新发展起来的第3代分子标记。已成为一类新的遗传标记,广泛应用于基因定位、克隆和遗传多样性研究。本文介绍了SNP的特性、检测方法及其在畜牧业研究生产中的广泛利用前景。并提出了SNP研究中遇到的一些问题。 相似文献
77.
T. Iwanaga †‡ A. McEuen† A. F. Walls† J. B. Clough† T. P. Keith§ S. Rorke† S. J. Barton† S. T. Holgate† J. W. Holloway † 《Clinical and experimental allergy》2004,34(7):1037-1042
BACKGROUND: Mast cell chymase has the potential to be an important mediator of inflammation and remodelling in the asthmatic lung. Previous studies have examined association between promoter polymorphism of the chymase gene (CMA1) and allergic phenotypes but the significance of this polymorphism is unclear. We have examined association of a CMA1 variant in relation to asthma in a large UK Caucasian family cohort. METHODS: A polymorphism of the CMA1 gene promoter (-1903G/A) was genotyped in 341 asthmatic families and in 184 non-asthmatic adults recruited from the UK PCR-RFLP based genotyping. Association with asthma diagnosis, atopy, specific and total IgE, and atopy and asthma severity was examined. RESULTS: Case-control studies did not reveal a significant difference in allele frequency between asthmatics and controls. A significant association was found between CMA1 genotypes and total IgE levels in subjects with self-reported eczema that remained significant after correction for multiple testing (median total serum IgE GG 297 kU/L, GA 144 kU/L, AA 48.4 kU/L, Pc=0.0032). CONCLUSION: These data suggest that CMA1 promoter polymorphism does not contribute to asthma susceptibility or severity but may be involved in regulating IgE levels in patients with eczema. 相似文献
78.
Lorraine N Clark Eneli Haamer Helen Mejia-Santana Juliette Harris Suzanne Lesage Alexandra Durr Sabine Janin Bs Katja Hedrich Elan D Louis Lucien J Cote Howard Andrews Stanley Fahn Cheryl Waters Blair Ford Steven Frucht William Scott Christine Klein Alexis Brice Hanno Roomere Ruth Ottman Karen Marder 《Movement disorders》2007,22(7):932-937
Parkin mutations account for the majority of familial and sporadic early onset Parkinson's disease (EOPD) cases with a known genetic association. More than 100 mutations have been described in the Parkin gene that includes homozygous, compound heterozygous, and single heterozygous mutations. We have designed a Parkin mutation genotyping array (gene chip) that includes published Parkin sequence variants and allows their simultaneous detection. The chip was validated by screening 85 PD cases and 47 controls previously tested for Parkin mutations. Similar genotyping microarrays have been developed for other genetically heterogeneous diseases including age-related macular degeneration. Here, we show the utility of a genotyping array for Parkinson's disease by analysis of 60 subjects from the Genetic Epidemiology of Parkinson Disease (GEPD) study that includes 15 early-onset PD case probands and 45 relatives. 相似文献
79.
目的构建+10Gz重复暴露大鼠脑差异表达基因的消减cDNA文库。方法本实验用SD大鼠,分别提取暴露组与对照组的总RNA,并分离纯化mRNA,应用抑制性消减杂交技术分离+10GI重复暴露大鼠脑差异表达基因eDNA片段并建立消减eDNA文库;利用PCR对随机挑选的75个白色菌落进行插入片段的验证,对其中70个克隆进行eDNA斑点杂交验证。结果所构建的eDNA文库扩增后包含约400个白色克隆和100个兰色克隆,随机挑选75个白色克隆入质粒载体后共获得70个阳性克隆。结论应用抑制性消减杂交技术成功构建了+10Gz重复暴露大鼠脑差异表达基因消减eDNA文库,为进一步筛选和克隆脑损伤相关基因奠定了基础。 相似文献
80.
Graph algorithms previously developed by the authors are adapted to simulate pedigrees similar to those used in genetic linkage studies which associate disease phenotypes with specific genomic locations. Pedigrees are chosen uniformly at random from the set of those with specified numbers of individuals and matings and which contain no loops. Summary statistics from pedigrees generated in this way can be used to check real pedigrees for anomalies due to biased sampling or phenotypic effects on the pedigree structure. 相似文献