Breast Cancer Genes

Abstract: The identification of familial breast cancer genes heralds an era of directed breast cancer treatment. Currently, two hereditary breast cancer genes have been identified, BRCA-1 and BRCA-2 . Although accounting for only approximately 5% of all breast cancers, they are being used to identify women with germ-line alterations that are at high risk of developing breast or ovarian cancer. With the identification of such genes comes a need for consideration of the ethical issues associated with testing. These genes are also being examined from a biochemical standpoint encompassing both their biological roles and biochemical pathways in which they reside. Such studies are likely to lead to novel breast cancer therapies.     

基于混合遗传算法的心脏病决策支持系统研究

将遗传算法和 BP算法相结合 ,建立了一个基于混合遗传算法的心脏病决策支持系统来鉴别诊断五种常见心脏病 (冠心病 ,高血压性心脏病 ,风湿性心脏病 ,慢性肺原性心脏病和先天性心脏病 )。一个含有 35 2份心脏病的数据库用来构建和测试了该系统。实验结果表明 ,构建的系统对这五种心脏病均有较好的诊断识别率 ,系统的平均识别准确性达 90 .6 % ,各疾病的用户准确性和程序准确性均大于 85 .0 % ,表现出良好的心脏病的临床诊断决策支持能力     

A biometrical genetic approach to chromosome analysis inDrosophila: Detection of epistatic interactions in geotaxis

Chromosome analysis has been widely used as a first step in eclucidating the genetic architecture of several behaviors ofDrosophila melanogaster. These chromosome studies have generally used incomplete designs or fairly simple statistical analyses. Here I reanalyze two data sets on geotaxis from Pyle (1978) and Ksander (1966) using a biometrical genetic design. Results from the biometrical genetic reanalysis suggest that individual differences in geotaxis might be due to genes on all three major chromosomes which show extensive epistatic interactions.     

Intraperitoneal infection with Salmonella abortusovis is partially controlled by a gene closely linked with the Ity gene.

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.     

Numerical comparisons of two formulations of the logistic regressive models with the mixed model in segregation analysis of discrete traits.

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.     

Detection of linkage under heterogeneity: comparison of the two-locus vs. admixture models.

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.     

猕猴实验性脑动脉硬化扫描电镜观察

本实验表明,猕猴高脂造型22—28个月,其大脑中动脉(Middle Cerebral Artery:MCA)内皮发生水肿、细胞间隙变宽,局部破裂等改变,中膜平滑肌细胞增生、迁移。老年高脂组病损程度较重,且中央支也表现出类似改变。结果提示,高血脂可以引起脑动脉硬化性改变,且病损程度与年龄因素密切相关。     

Season of birth interacts with measures of inbreeding in multiplex schizophrenia pedigrees: evidence from genetic isolates in Daghestan

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.