Evaluation of Candidate Gene Effects for Beef Backfat via Bayesian Model Selection

Candidate gene approaches provide tools for exploring and localizing causative genes affecting quantitative traits and the underlying variation may be better understood by determining the relative magnitudes of effects of their polymorphisms. Diacyglycerol O-acyltransferase 1 (DGAT1), fatty acid binding protein (heart) 3 (FABP3), growth hormone 1 (GH1), leptin (LEP) and thyroglobulin (TG) have been previously identified as genes contributing to genetic control of subcutaneous fat thickness (SFT) in beef cattle. In the present research, Bayesian model selection was used to evaluate effects of these five candidate genes by comparing competing non-nested models and treating candidate gene effects as either random or fixed. The analyses were implemented in SAS to simplify the programming and computation. Phenotypic data were gathered from a F₂ population of Wagyu × Limousin cattle. The five candidate genes had significant but varied effects on SFT in this population. Bayesian model selection identified the DGAT1 model as the one with the greatest model probability, whether candidate gene effects were considered random or fixed, and DGAT1 had the greatest additive effect on SFT. The SAS codes developed in the study are freely available and can be downloaded at: http://www.ansci.wsu.edu/programs/.Mention of a proprietary product does not constitute a guarantee or warranty of the product by USDA, Montana AES, or the authors and does not imply its approval to the exclusion of other products that may also be suitable.     

A Mouse Model for the Metabolic Effects of the Human Fat Mass and Obesity Associated FTO Gene

Human FTO gene variants are associated with body mass index and type 2 diabetes. Because the obesity-associated SNPs are intronic, it is unclear whether changes in FTO expression or splicing are the cause of obesity or if regulatory elements within intron 1 influence upstream or downstream genes. We tested the idea that FTO itself is involved in obesity. We show that a dominant point mutation in the mouse Fto gene results in reduced fat mass, increased energy expenditure, and unchanged physical activity. Exposure to a high-fat diet enhances lean mass and lowers fat mass relative to control mice. Biochemical studies suggest the mutation occurs in a structurally novel domain and modifies FTO function, possibly by altering its dimerisation state. Gene expression profiling revealed increased expression of some fat and carbohydrate metabolism genes and an improved inflammatory profile in white adipose tissue of mutant mice. These data provide direct functional evidence that FTO is a causal gene underlying obesity. Compared to the reported mouse FTO knockout, our model more accurately reflects the effect of human FTO variants; we observe a heterozygous as well as homozygous phenotype, a smaller difference in weight and adiposity, and our mice do not show perinatal lethality or an age-related reduction in size and length. Our model suggests that a search for human coding mutations in FTO may be informative and that inhibition of FTO activity is a possible target for the treatment of morbid obesity.     

麦芽品质性状的遗传模型及其分析方法

本文提出分析大麦芽品质性状世代平均数的遗传模型,根据麦芽性状的特点,该模型将控制麦芽性状的总遗传效应分解为萌动胚基因效应和胚乳基因效应。     

麦蚜复合种群动态预测的Fuzzy推理模式及应用

本研究利用了山东省曲阜地区１９８２－１９９４年共１３年的资料,选用了３月下旬至４月上旬平均气温（℃）和４月７上旬温湿系数作为预报因子,麦蚜蚜量始达５００（头／丰株）的日期作为预报对象组建Ｆｕｚｚｙ推理模式。对历史资料进行回代验证,其历史拟合率达１００％。将１９９５年的观测数据作为独立样本进行试报,预测结果与实际一致。为麦蚜复合种群动态预测提供了一种新的研究方法。     

Complex Study of Drosophila Mutants in the agnostic Locus: A Model for Coupling Chromosomal Architecture and Cognitive Functions

After the devastation of genetics in our country, Academician Leon A. Orbeli has provided an opportunity for the studies on evolutionary conservatism of genes controlling the main properties of the higher nervous activity and conditioning. For the last few years, determination and bioinformatic analysis of genome sequences in the plant, worm, Drosophila, and human genome have revealed, indeed, a high interspecies homology of genes. Studies on Drosophila mutants have shown that components of intracellular signalization systems regulating neuronal functions and gene expression are organized in supramolecular complexes. It has become evident that the chromosomal architecture predetermines the appearance of deletions, duplications, insertions, and translocations and, therefore, plays an important role not only in evolution but also in generating human pathological syndromes with multiple manifestations, including cognitive dysfunctions. There appeared a new approach, comparative genomics, that allows revealing functions of human disease genes on the basis of their sequence homology to the known Drosophila gene with various well-studied mutant phenotypes. For this reason, the Drosophila genes should be saturated with mutant phenotypes, and these are to be studied in comparison with the chromosomal architecture. Our complex behavioral and molecular-genetic study of spontaneous, induced, and P-insertional mutations in the Drosophila agnostic locus and the bioinformatic analyses of genomic sequences has allowed us to assign the locus to the Drosophila genomic scaffold AE003489 from the 11AB X-chromosomal region that contains the CG1848 gene coding for LIM-kinase 1. Mutations, insertions, and deletions in the agnostic locus lead to an increased activity of Ca²⁺/calmodulin-dependent PDE1, resistance to ether, an inactivator of synaptic transmission, impairments of the brain structures, learning and memory defects in conditioned courtship suppression paradigm, alterations in sound production and in structural-functional chromosomal organization. Therefore, the agnostic locus represents a model to study the human Williams syndrome with multiple dysfunctions due to a contiguous deletion in the 7q11.23 spanning 17 genes, among them the gene for LIM-kinase 1 presumed to be responsible for cognitive defects. The Williams syndrome is considered to be a most efficient model to study human cognition, human genome organization, and evolution.     

多元性状同胞对连锁分析方法及其在原发性高血压基因定位数据中的应用

提出新的以广义最小二乘法原理处理同胞对数据间的相关性,以多元响应回归的方法处理多个性状数据间的相关性的多元性状同胞对连锁分析方法,模型的参数估计使用MCMC方法．并把此模型应用于原发性高血压基因定位的实际数据中．结果表明,与把多元性状拆成单一性状进行分析的方法相比,本文的方法可以提高估计的精度和检验的效能．     

Using the Gene Ontology for Microarray Data Mining: A Comparison of Methods and Application to Age Effects in Human Prefrontal Cortex

One of the challenges in the analysis of gene expression data is placing the results in the context of other data available about genes and their relationships to each other. Here, we approach this problem in the study of gene expression changes associated with age in two areas of the human prefrontal cortex, comparing two computational methods. The first method, "overrepresentation analysis" (ORA), is based on statistically evaluating the fraction of genes in a particular gene ontology class found among the set of genes showing age-related changes in expression. The second method, "functional class scoring" (FCS), examines the statistical distribution of individual gene scores among all genes in the gene ontology class and does not involve an initial gene selection step. We find that FCS yields more consistent results than ORA, and the results of ORA depended strongly on the gene selection threshold. Our findings highlight the utility of functional class scoring for the analysis of complex expression data sets and emphasize the advantage of considering all available genomic information rather than sets of genes that pass a predetermined "threshold of significance."     

A Model of Ocular Dominance Column Development by Competition for Trophic Factor: Effects of Excess Trophic Factor with Monocular Deprivation and Effects of Antagonist of Trophic Factor

Recent experimental evidence has implicated neurotrophic factors (NTs) in the competitive process believed to drive the development of ocular dominance (OD) columns. Application of excess amounts of particular NTs can prevent the segregation process, suggesting that they could be the substance for which geniculocortical afferents compete during development. We have previously presented a model that accounts for normal OD development as well as the prevention of that development with excess NT. The model uses a Hebbian learning rule in combination with competition for a limiting supply of cortical trophic factor to drive OD segregation, without any weight normalization procedures.Subsequent experimental evidence has further suggested that NTs may be causally involved in the competitive process. Application of NT antagonist can prevent OD columns by causing inputs from both eyes to be eliminated, suggesting that NTs may be the substance for which geniculocortical afferents compete. Also, excess NT can mitigate the shift to the open eye normally caused by monocular deprivation (MD). In this article, we show that the current model can account for these subsequent experiments. We show that deprivation of NT causes inputs from both eyes to decay and that excess NT can mitigate the shift to the open eye normally seen with MD. We then present predictions of the model concerning the effects of NT on the length of the critical period during which MD is effective. The model presents a novel mechanism for competition between neural populations inspired by particular biological evidence. It accounts for three specific experimental results, and provides several testable predictions.